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CONTENTS
CHAPTER
1.
PAGE
IONIC AND ORGANOMETALLIC-CATALYZED ORGANOSILANE REDUCTIONS Gerald L. Larson and James L. Fry . . . . . . . . . . . . . . . . . . . . . .
1
CUMULATIVE CHAPTER TITLES BY VOLUME . . . . . . . . . . . . . . . . . . . . . . . 739 AUTHOR INDEX, VOLUMES 1–71 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 753 CHAPTER AND TOPIC INDEX, VOLUMES 1–71 . . . . . . . . . . . . . . . . . . . . . . 759
vii
CHAPTER 1
IONIC AND ORGANOMETALLIC-CATALYZED ORGANOSILANE REDUCTIONS GERALD L. LARSON Gelest, Inc., Morrisville, Pennsylvania 19067 JAMES L. FRY 6016 Trotwood Court, Fort Collins, Colorado 80524
CONTENTS ACKNOWLEDGMENTS . . . . . . INTRODUCTION . . . . . . . . . . . . . . MECHANISM General Considerations . . . . . Role of Trivalent Silicon Species . . . Role of Hypervalent Silicon Species . . Role of O/N-Silylated Cationic Intermediates Role of Metal Catalysts . . . . . SCOPE AND LIMITATIONS . . . . Reduction of Substituted Alkanes . . . Alcohols to Alkanes . . . . . Alkyl Halides and Triflates to Alkanes . Reduction of Unsaturated Hydrocarbons . Alkenes to Alkanes . . . . . Alkynes to Alkanes . . . . . Cyclopropanes to Alkanes . . . . Aromatic Substrates . . . . . Miscellaneous Unsaturated Substrates . Reduction of Ethers . . . . . Reduction of Allyl Acetates . . . . Reduction of Carboxylic Acids . . . Reduction of Acid Halides and Acid Anhydrides Reduction of Esters and Lactones . . . Reduction of Aldehydes . . . . Reduction to Alcohols . . . .
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[email protected] [email protected] Organic Reactions, Vol. 71, Edited by Scott E. Denmark et al. 2008 Organic Reactions, Inc. Published by John Wiley & Sons, Inc. 1
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PAGE 5 5 6 6 7 9 11 11 12 12 12 27 32 32 45 46 48 49 50 51 51 53 53 56 56
2
ORGANIC REACTIONS
Reductive Amidation of Aldehydes . . . . . . . . Reductive Esterification . . . . . . . . . . Reductive Etherification . . . . . . . . . . Reduction to Alkanes . . . . . . . . . . Reduction to Methylene Halides . . . . . . . . Reductive Amination . . . . . . . . . . . Reductive Thiolation . . . . . . . . . . . Reduction of Ketones . . . . . . . . . . . Reduction to Alcohols . . . . . . . . . . Reductive Amidation . . . . . . . . . . . Reductive Esterification . . . . . . . . . . Reductive Etherification . . . . . . . . . . Reductive Silylation . . . . . . . . . . . Reduction to Halocarbons . . . . . . . . . . Reduction to Alkanes . . . . . . . . . . Reductive Amination . . . . . . . . . . . Reductive Thiolation . . . . . . . . . . . Miscellaneous Ketone Reductions . . . . . . . . Reduction of Amides . . . . . . . . . . . Reduction of α,β-Unsaturated Aldehydes . . . . . . . Reduction of α,β-Unsaturated Ketones . . . . . . . . Reduction of α,β-Unsaturated Esters . . . . . . . . Reduction of α,β-Unsaturated Amides . . . . . . . . Reduction of α,β-Unsaturated Nitriles . . . . . . . . Reduction of Acetals, Ketals, Hemiacetals, Hemiketals, and Orthoesters . Reduction of Aminals and Hemiaminals . . . . . . . Reduction of Enamines . . . . . . . . . . . Reduction of Imines . . . . . . . . . . . Reduction of Oximes . . . . . . . . . . . Reduction of Nitroalkanes . . . . . . . . . . Reduction of Miscellaneous Nitrogen-Containing Compounds . . . Reduction of Miscellaneous Sulfur-Containing Compounds . . . . Reduction of Small-Ring Heterocycles . . . . . . . . Asymmetric Reduction of Ketones . . . . . . . . Asymmetric Reduction of α,β-Unsaturated Ketones . . . . . Asymmetric Reduction of α,β-Unsaturated Esters and Lactones . . . Asymmetric Reduction of α,β-Unsaturated Lactams . . . . . Asymmetric Reduction of Imines . . . . . . . . . . . . . . . . . . COMPARISON WITH OTHER METHODS Asymmetric Hydrogenation of Olefins . . . . . . . . Asymmetric Hydrogenation of Ketones . . . . . . . . Asymmetric Hydrogenation of Enol Acetates . . . . . . . Asymmetric Hydrogenation of α,β-Unsaturated Acids . . . . . Asymmetric Hydrogenation of Acetamidoacrylates . . . . . Asymmetric Hydrogenation of Enamides . . . . . . . Asymmetric Hydrogenation of Imines . . . . . . . . . . . . . . . . . . EXPERIMENTAL CONDITIONS . . . . . . . . . . EXPERIMENTAL PROCEDURES 2-Decyl-5-methoxy-1-naphthol [Reduction of a Secondary Benzylic Alcohol to a Methylene Group with Concomitant Loss of a MOM Protecting Group] . Cyclohexane [Aluminum Chloride Catalyzed Reduction of a Dichloroalkane to a Hydrocarbon] . . . . . . . . . . . .
63 63 64 69 72 73 74 74 74 79 80 80 82 84 84 85 86 86 87 88 88 93 96 96 97 99 100 101 102 102 103 104 105 105 108 109 110 110 111 111 112 116 116 117 118 119 120 121
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121
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121
ORGANOSILICON HYDRIDE REDUCTIONS 1-Dodecanol [Fluoride-Promoted Reduction of an Ester to an Alcohol] . . Dibenzyl Ether [Brønsted Acid Promoted Reduction of an Aldehyde to a Symmetrical Ether] . . . . . . . . . . . . . . Ethyl Benzyl Ether [Brønsted Acid Promoted Reduction of an Aldehyde to an Unsymmetrical Ether] . . . . . . . . . . . 1-Heptyl 3-Phenylpropyl Ether [Electrogenerated Acid-Promoted Reduction of an Aldehyde to an Unsymmetrical Ether] . . . . . . . . Dicyclohexyl Ether [Brønsted Acid Promoted Reduction of a Ketone to a Symmetrical Ether] . . . . . . . . . . . . . . Benzyl 3-Phenylpropyl Ether [Trityl Perchlorate Catalyzed Reduction of an Aldehyde to an Unsymmetrical Ether] . . . . . . . . . . Di-n-pentyl Ether [TMSI-Catalyzed Reduction of an Aldehyde to a Symmetrical Ether]. . . . . . . . . . . . . . . Cyclohexyl Ethyl Ether [TMSI-Catalyzed Reduction of a Ketone to an Unsymmetrical Ether] . . . . . . . . . . . . . . 4-Methylbenzyl Chloride [Reductive Halogenation of an Aldehyde to a Benzyl Chloride] . . . . . . . . . . . . . . (1R,2S)-2-[(Ethoxycarbonyl)amino]-1-phenyl-1-propanol [Brønsted Acid Promoted Reduction of an α-Amino Ketone to an Erythro α-Hydroxy Amine] . . . Phenylcyclopentane [Brønsted Acid Catalyzed Reduction of an Alkene to an Alkane] . . . . . . . . . . . . . . n-Hexadecane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of an Acid Chloride to an Alkane] . . . . . . . . . . . . . n-Dodecane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of a Carboxylic Acid to an Alkane] . . . . . . . . . . . . . 4-Iodobenzyloxytriethylsilane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of a Carboxylic Acid to a Benzyl Triethylsilyl Ether] . . . . . . N -(Phenylmethylsilyl)-1,2,3,4-tetrahydropyridine [Reduction of a Pyridine] . Camphor [Reduction of an α-Bromo Ketone to a Ketone] . . . . . 2-Phenyl-5-decylpyrimidine [Reduction of an Aryl Triflate to an Arene] . . n-Hexadecane and 1-(Triethylsiloxy)hexadecane [Reduction of a Symmetrical Ether] 3-Phenyl-1-propanol [Reduction of a Carboxylic Acid to an Alcohol] . . Cys(SBu-t)Gly [Reductive Deprotection of Boc and tert-Butyl Ester Groups in the Presence of a tert-Butyl Sulfide] . . . . . . . . . N -Boc-cyclododecylamine [Reductive Boc-protection of an Oxime] . . . (3R)-N -Acetyl-3-(tert-butyldimethylsiloxy)pyrrolidine [Reduction of an Aminal to an Amine] . . . . . . . . . . . . . . 3,5-Dimethyl-l-cyclohexen-l-yl Dimethylphenylsilyl Ether [Reductive 1,4-Hydrosilylation of an Enone] . . . . . . . . . 6,8-Dioxabicyclo[3.2.1]octan-4-one [1,2-Reduction of an Enone in the Presence of an Acetal] . . . . . . . . . . . . . . N -(exo-2-Norbornyl)acetamide [Reductive Amidation of a Ketone] . . . Dihydro-β-Ionone [1,4-Reduction of an α,β-Unsaturated Ketone] . . . β-Ionol [1,2-Reduction of an α,β-Unsaturated Ketone] . . . . . Undec-10-enal [Reduction of an Amide to an Aldehyde] . . . . . 4-Phenylpent-1-ene [Reductive Allylation of an Aryl Ketone] . . . . 6-Phenylhex-1-ene [Reduction of an Aliphatic Ketone Function to a Methylene Function] . . . . . . . . . . . . . . 10-Undecen-1-ol [Reduction of an Ester to an Alcohol] . . . . . Tricarbonyl(1-endo-allyltetralin)chromium [Stereoselective Reduction of an Alcohol to a Hydrocarbon] . . . . . . . . . . . . . 5-Methoxytetralin [Partial Reduction of a Substituted Naphthalene to a Tetralin]
3 121 122 122 122 123 123 123 124 124 125 125 125 126 126 126 127 127 127 128 128 128 129 129 129 130 130 130 131 131 131 132 132 132
4
ORGANIC REACTIONS
1,2,3-Trideoxy-D-ribo-hex-1-enopyranose Diacetate [Reduction of an Allyl Ester] 6-(2-Butyl)-4-hydroxy-3-ethyl-2-pyrone (Germicidin) [Reduction of a Ketone Carbonyl to a Methylene Group in a Multifunctional Compound] . . . . . 1-(1-Chloroethyl)-4-nitrobenzene [Deoxygenative Chlorination of a Ketone] . Methyl 2-(Phenylcarbamoyl)butanoate [Hydrocarbamoylation of an α,β-Unsaturated Ester] . . . . . . . . . . . . . . Benzyl Bromide [Reductive Bromination of an Acetal] . . . . . 2-(Benzyloxy)-3-bromo-5-[(2-ethoxycarbonyl)ethyl]phenyl Ethyl Carbamate [Reduction of an Enamide to an Amide] . . . . . . . . . . 3-Nitrobenzylamine [Reduction of an Imine to an Amine] . . . . . Cyclohexyl Iodide [Iodoreduction of an Oxirane to an Iodoalkane] . . . (R)-3,3-Dimethyl-5-(2-phenylethyl)cyclohexanone [Asymmetric 1,4-Reduction of an Enone] . . . . . . . . . . . . . . . . . . . . . . . . . . . TABULAR SURVEY Chart 1. Catalysts and Ligands Used in Tables . . . . . . . Chart 2. Organosilane Compound Designations Used in Tables . . . . Table 1. Organosilane Reduction of Alkenes . . . . . . . . Table 2. Organosilane Reduction of Alkynes . . . . . . . . Table 3. Organosilane Reduction of Aromatic Hydrocarbons . . . . . Table 4. Organosilane Reduction of Halocarbons . . . . . . . Table 5. Organosilane Reduction of Alcohols . . . . . . . Table 6. Organosilane Reduction of Ethers . . . . . . . . Table 7. Organosilane Reduction of Allyl Esters . . . . . . . Table 8. Organosilane Reduction of Acids . . . . . . . . Table 9. Organosilane Reduction of Acid Halides . . . . . . . Table 10. Organosilane Reduction of Esters and Lactones . . . . . Table 11. Organosilane Reduction of Aldehydes . . . . . . . Table 12. Organosilane Reduction of Ketones . . . . . . . Table 13. Organosilane Reduction of Amides . . . . . . . Table 14. Organosilane Reductive Amination of Aldehydes and Ketones . . Table 15. Organosilane Reduction of α,β-Unsaturated Aldehydes . . . . Table 16. Organosilane Reduction of α,β-Unsaturated Ketones . . . . Table 17. Organosilane Reduction of α,β-Unsaturated Esters . . . . . Table 18. Organosilane Reduction of α,β-Unsaturated Amides . . . . Table 19. Organosilane Reduction of α,β-Unsaturated Nitriles . . . . Table 20. Organosilane Reduction of Acetals, Ketals, and Hemiketals . . . Table 21. Organosilane Reduction of Aminals and Hemiaminals . . . . Table 22. Organosilane Reduction of Enamines . . . . . . . Table 23. Organosilane Reduction of Imines . . . . . . . . Table 24. Organosilane Reduction of Hydroxylimines . . . . . . Table 25. Organosilane Reduction of Nitroalkanes . . . . . . . Table 26. Organosilane Reduction of Miscellaneous Nitrogen Compounds . . Table 27. Organosilane Reduction of Miscellaneous Sulfur Compounds . . . Table 28. Organosilane Reduction of Small-Ring Compounds . . . . Table 29. Miscellaneous Organosilane Reductions . . . . . . . Table 30. Asymmetric Organosilane Reduction of Ketones . . . . . Table 31. Asymmetric Organosilane Reduction of α,β-Unsaturated Ketones . . Table 32. Asymmetric Organosilane Reduction of α,β-Unsaturated Esters . . Table 33. Asymmetric Organosilane Reduction of α,β-Unsaturated Lactams . . Table 34. Asymmetric Organosilane Reduction of Imines . . . . . . . . . . . . . . . . . . . REFERENCES
133 133 134 134 134 135 135 136 136 136 141 151 152 175 182 192 209 242 252 258 262 265 302 345 446 455 466 468 509 531 533 534 571 576 582 593 599 602 610 611 616 618 687 694 704 705 719
ORGANOSILICON HYDRIDE REDUCTIONS
5
ACKNOWLEDGMENTS
The authors thank Mr. Thomas C. Johns of E. I. du Pont de Nemours and Company, Mr. Christopher W. Fry, Ms. Diane Micham, and the Department of Chemistry, University of Pennsylvania, for valuable assistance in the literature survey. INTRODUCTION
The purpose of this chapter is to present a critical review of synthetically useful variations of ionic methods for hydrogenation of organic compounds. In practice, ionic hydrogenation involves the formal introduction of hydride from a donor source to an electron-deficient carbon center. The electrophilic centers can be formed by the departure of a leaving group (nucleofuge) from a saturated center or by the addition of an electrophile to a multiple bond. In the former mechanism, substitution of hydrogen for the leaving group is the net chemical consequence. In the latter, addition across the multiple bond is the result. In this chapter, we cover the use of organosilicon hydrides as the source of ionic hydride with the goal of completing and updating earlier review works on the subject.1 – 4 Similar chemistry is observed when molecular hydrogen5,6 or various hydrocarbons7 – 9 are used as hydride sources; these methods have been reviewed previously and are not covered herein. The use of organosilicon hydride-metal catalyst mixtures10 – 12 for effecting reductions is included in this review, but use of trichlorosilane-tertiary amine combinations13 is not. Organosilicon compounds with at least one Si-H bond (called hydrosilanes, organosilicon hydrides, or simply silanes) have the ability to serve as mild air- and water-stable sources of hydride and thus have reducing properties. For example, triethylsilane is reported to reduce a variety of inorganic metal salts directly to the free metals.14,15 Even the hexachloroantimonate anion can be reduced to Sb(0) upon contact with this silane.16 Organotellurium chlorides are reduced to tellurium metal by a number of organosilicon hydrides.17 Reaction of organosilicon hydrides with strong Brønsted acids leads to decomposition of the silane and the production of hydrogen gas.14 In general, organosilicon hydrides do not undergo spontaneous reactions with organic compounds unless the organic substrate is a reasonably strong electrophile or the silane has been first activated by the interaction of a nucleophilic species with the silicon center. The organosilicon hydrides are covalent compounds that have little or no nucleophilic properties of their own. Aside from the parent silane, SiH4 , which is pyrophoric, the organosilicon hydrides are fairly innocuous compounds whose physical properties bear resemblance to their hydrocarbon analogs. Thus, their physical and chemical reducing properties differ from those of many familiar metal hydride reducing agents.18,19 The use of organosilicon hydrides often provides a means of effecting reductions of organic substrates under very mild conditions and with excellent functional group selectivity. Consideration of the nature of the Si–H bond provides insight into the chemical behavior of organosilicon hydrides. Comparison of the bond strengths as
6
ORGANIC REACTIONS
represented by bond dissociation energy (BDE) of hydrosilanes with those of hydrocarbon analogs shows that, in general, the Si–H bond is not much weaker than the C–H bond. Thus, the BDE values for the respective Si–H bonds in TMS–H and (C2 H5 )3 Si–H are 90.320 and 90.1 kcal/mol21 compared with a value of approximately 92 kcal/mol20 for the tertiary C–H bond in (CH3 )3 C–H. On the other hand, there is a significant difference between the polarization characteristics of the Si–H and C–H bonds.22 Compared to the Pauling electronegativity of hydrogen (2.20), the electronegativity of carbon (2.50) is greater and that of silicon (1.90) is less.23 Carbon-hydrogen bonds are thus polarized in the direction Cδ− –Hδ+ , whereas Si–H bonds are Siδ+ –Hδ− . As will be seen, this enhanced hydridic nature manifests itself in the chemical behavior of essentially all hydrosilanes. Limited studies of the germanium and tin hydride analogs of the silicon hydrides show that they share this ability to function as hydride sources in ionic hydrogenations; however, their relatively greater reactivity toward acids appears to restrict their practical applications in organic synthesis.24,25 MECHANISM
General Considerations The mechanistic discussion of silane reductions will be limited to those of cationic reductions, thus excluding the many silane reductions that involve metal catalysis. Since tetravalent organosilicon hydrides intrinsically lack nucleophilicity, they react only with atomic centers that are substantially electron deficient, for example, carbocations. Because of this, organosilicon hydride reductions are potentially very selective. The “ionic” reductions of organic compounds by organosilicon hydrides are understood on the basis of two mechanisms. In the first, substitution by hydrogen of a leaving group bonded to a saturated carbon occurs. This path may be called a σ -route as it involves the stepwise cleavage of a σ -bond to a saturated center and the intervention of a carbocation intermediate that is captured by donation of hydride from the organosilicon hydride (Eq. 1). Alternatively, addition of an electrophile/hydride pair takes place across a multiple bond. This path may be termed a π-route (Eq. 2). Complexation of an electrophile to one end of a π-bond is followed by capture of the intermediate cation or complex by organosilicon hydride. The electrophile may be as simple as a proton or be one of a variety of Lewis acids or alkylating agents. The group Y can be C, O, N, or S. Sometimes the product of Eq. 2 can continue reacting by way of Eq. 1, with the moiety Y–E acting as a leaving group. When this occurs, the net effect is to replace the C=Y functionality with CH2 . The normal caveats regarding carbocation behavior such as the possible occurrences of eliminations, skeletal isomerizations, and bimolecular reactions prior to capture by hydride must be expected in all of these scenarios. X
–X–
+
R3SiH
H
(Eq. 1)
ORGANOSILICON HYDRIDE REDUCTIONS + Y
Y
+
R3SiH
Y
H
(Eq. 2)
Y
E
E
7
E
It is necessary for the intermediate cation or complex to bear considerable carbocationic character at the carbon center in order for effective hydride transfer to be possible. By carbocationic character it is meant that there must be a substantial deficiency of electron density at carbon or reduction will not occur. For example, the sesquixanthydryl cation 1,26 dioxolenium ion 2,27 boron-complexed imines 3, and O-alkylated amide 4,28 are apparently all too stable to receive hydride from organosilicon hydrides and are reportedly not reduced (although the behavior of 1 is in dispute29 ). This lack of reactivity by very stable cations toward organosilicon hydrides can enhance selectivity in ionic reductions.
O
O + + O O
O 1
R
H
EtO
Ph
Et
N+ BF3–
Et
N+ Et
2
3
4
Role of Trivalent Silicon Species The overall stoichiometry of hydride transfer from a silicon center to an electron-deficient carbon center is quite straightforward. Almost without exception, it appears that there is simple interchange of hydride to the carbocation while the silicon center receives the elements of the carbocation’s counterion (Eq. 3). R 3C + X –
+
R'3SiH
R3CH
+
R'3SiX
(Eq. 3)
When the counterion is complex, for example metal-halogen anions such as BF4 − , the most electronegative portion of the counterion becomes attached to the silicon center. Because of this attachment, it is natural to consider the intermediacy of a silicenium cation (silylium or silylenium ion) intermediate in such reactions (Eq. 4). Bond energies derived from electron impact studies indicate that Eq. 4 is exothermic in the gas phase by about 8 kcal/mol.26,29 There seems little doubt that trivalent silicon-centered cationic species do exist in the gas phase30,31 or that processes similar to that shown in Eq. 4 do occur there.32,33 Me3C+
+ (CH3)3SiH
(CH3)3CH
+ (CH3)3Si+
(Eq. 4)
The existence of trivalent silicenium cations as reactive species in solution is more controversial. Many early attempts to demonstrate the solution-phase existence of stable silicenium ions by using techniques analogous to those successfully applied to carbocation formation failed.34 – 36 Other reports of attempts
8
ORGANIC REACTIONS
to generate silicenium ions in solution under stable ion conditions37 – 46 and in solvolyses47 are more convincing, but not without controversy.48 – 51 The singlecrystal X-ray determination of a non-planar triethylsilylium moiety paired in the crystalline state with the tetrakis(pentafluorophenyl)borate gegenion and toluene solvate stirred much debate about its interpretation and extension to reaction systems.52,53 Recent crystallographic evidence supports the notion of a threecoordinate structure of a trimesitylsilylium cation paired with a carborane anion in the solid phase.54,55 The balance of experimental evidence seems to indicate that, whereas trivalent silicenium cations may have fleeting existence as reaction intermediates, it is unlikely that they exist as stable, long-lived species in solution.56 The failure to observe such trivalent species in solution is related to the very strong ability of electron-deficient silicon centers to coordinate with the media in which they are formed.53,57,58 This is true even in solvents that exhibit little or no nucleophilicity toward carbocations and is further enhanced by the relatively long bond lengths to silicon centers that allow a close approach by coordinating species.53 The available experimental information is suggestive, but not unambiguously conclusive, of the intervention of electron-deficient silicon-centered species that may resemble silicenium cations in simple hydride exchanges occurring in solvents with low coordinating abilities. For example, substituted triarylmethane derivatives such as chlorotriphenylmethane (trityl chloride) undergo reduction through halogen-hydride exchange with organosilicon hydrides. The reactions proceed more rapidly in solvents with high ionizing power, but are kinetically first order with respect to both organosilicon hydride and triarylmethane derivative in benzene solvent.59 In benzene, the exchange of halogen with hydride occurs with retention of configuration at the silicon center.60 These results have led to the suggestion that the exchanges proceed by way of a four-center transition state 5, in which there is simultaneous attack by the halide of the carbocation-halide ion pair on the silicon center as hydride undergoes transfer to the carbocation center.60 H
Ph3Si +
Cl–
CPh3
5
Simple variation of the solvent has a very significant effect on the stereochemistry at the silicon center for these exchange reactions. The stereochemistry changes from essentially complete retention to inversion and even to racemization. For example, in dichloromethane the halogen is delivered to the silicon center with complete racemization.61 This implies that the degree of “tightness” of the carbocation-counterion pair must change depending on the solvent. Organosilicon hydride reductions of preformed stable carbocations such as triphenylmethyl (trityl) tetrafluoroborate and hexafluoroantimonate salts are rapid
ORGANOSILICON HYDRIDE REDUCTIONS
9
and essentially quantitative.62,63 Reductions of these and similar stable ions in dichloromethane/trifluoroacetic acid (TFA) show primary deuterium kinetic isotope effects in the range kH /kD = 1.2764 to 1.8965 at room temperature, whereas effects equal to kH /kD = 1.50–2.33 are seen for the reduction of diarylcarbenium ions with deuteriosilanes at −70◦ .66 The kinetic rate dependence for similar reactions in acetic acid is first order in both the cation and the silane. The rates of a series of substituted arylsilanes correlate with σ constants, but not with σ + constants, to produce Hammett plots with ρ = −1.84 for triarylsilanes and ρ = −1.0165 to −2.4666 for aryldimethylsilanes. These results are interpreted to mean that the reactions occur through a four-center transition state in which the silicon center assumes a trigonal-bipyramidal shape with hydride exiting from an equatorial position while the carbocation’s counterion approaches axially.65 Trityl and tropylium (cycloheptatrienyl) cation salts having complex metalhalide anions such as SbX6 − , AsF6 − , PF6 − , FeCl4 − , and BF4 − undergo reduction with trialkylsilanes and aryldialkylsilanes at rates that are independent of the nature of the anion or of ring strain in the organosilicon hydride, are kinetically first order with respect to both cation and organosilicon hydride, and that display primary deuterium kinetic isotope effects of kH /kD = 1.41–1.49 in dichloromethane.67,68 It is argued that these reactions proceed by way of a threestep mechanism involving a rate-determining single-electron transfer step69 to create a charge-transfer complex between the carbocation and the organosilicon hydride followed by a faster transfer of hydride to the carbon center and the creation of a silicenium ion intermediate that is then rapidly captured by the counterion present (Eq. 5).68 Others regard this argument as doubtful compared to the polar mechanism in which Si–H bond cleavage is rate determining.66 + R'3SiH + R3C
R'3SiH + 3Si
R'
+ CR3
H CR3
slow + 3Si + R3CH
(Eq. 5)
R'
Uncertainties in understanding the exact mechanistic details of these reactions are sure to stimulate continued work to define the nature of trivalent silicon cations in ionic reductions by organosilicon hydrides. Role of Hypervalent Silicon Species It is well known that strong electrophiles such as carbocations are reduced by organosilicon hydrides (Eq. 1).3,70,71 On the other hand, simple mixtures of organosilicon hydrides and compounds with weakly electrophilic carbon centers such as ketones and aldehydes are normally unreactive unless the electrophilicity of the carbon center is enhanced by complexation of the carbonyl oxygen with Brønsted acids3,70 – 73 or certain Lewis acids (Eq. 2).1,70,71,74,75 Using these acids, hydride transfer from the silicon center to carbon may then occur to give either alcohol-related or hydrocarbon products.
10
ORGANIC REACTIONS
Alternatively, unreactive mixtures of organosilicon hydrides and carbonyl compounds react by hydride transfer from the silicon center to the carbon center when certain nucleophilic species with a high affinity for silicon are added to the mixture.76 – 94 This outcome likely results from the formation of valence-expanded, pentacoordinate hydrosilanide anion reaction intermediates that have stronger hydride-donating capabilities than their tetravalent precursors (Eq. 6).22,95 – 101 R3SiH + Nu–
1. R'2C=O
R3SiHNu–
2. H2O
R3SiNu
+ R'2CHOH
(Eq. 6)
The bicyclic silatrane molecule 6, which has a strong degree of coordination between the silicon center and the nitrogen bridgehead, has been shown to have unusually strong reducing properties compared to normal tetravalent organosilicon hydrides.102 The hypothesis that valence-expanded pentacoordinate silicon species are the actual reducing species76,77,83 is plausible, for such species are well known.96,99,101,103 – 107 Other examples are known of the enhanced reducing powers of organosilicon hydrides that undergo intramolecular coordination and expansion to pentavalent82 and even hexavalent states.84,101,108 – 111
:
N
OO
Si O H 6
A variety of nucleophilic species cause valence expansion of organosilanes and the enhancement of reducing reactivity. These include formate, thiocyanate, tartrate, and phthalate salts,78 as well as alkoxides91,92,96,99,107 and catecholates.93 The strong propensity of fluoride ion to cause silicon centers to undergo valence expansion95,112 makes it especially effective in activating organosilicon hydrides as reducing agents. Aldehydes, ketones, and esters may all be reduced by such a technique, frequently with excellent functional group and stereochemical selectivity.76 – 89 The valence-expanded silicon intermediate retains some measure of stereochemical integrity up to the point of hydride transfer as evidenced by the small degrees of asymmetric induction that are observed in the reduction of prochiral ketones coupled with similar degrees of chirality found at the silicon center.85 The transfer of hydride from the silicon center to the carbonyl carbon takes place in the rate-determining step as judged by the primary deuterium kinetic isotope effect of 1.50 observed in the fluoride-induced reduction of acetophenone with dimethylphenylsilane-d1 .88 There is also evidence that the pentacoordinate silicon hydride can serve as a single-electron-transfer donor since radical-coupling products are sometimes obtained, although the general importance of this process is open to question.89,99
ORGANOSILICON HYDRIDE REDUCTIONS
11
A diaryldihydrosilane with a hexacoordinated silicon center, produced through intramolecular coordination, is reported not to react with benzaldehyde, although the silane is capable of reducing silver ion to silver metal.113 There is also a report of a heptacoordinate silicon hydride species with the ability to transfer hydride to trityl cation while remaining inactive toward methanol.108,114 Role of O/N-Silylated Cationic Intermediates An interesting variation of the reaction mechanisms discussed above has been offered following studies of the hydrosilation reductions of aldehydes, ketones, and esters to their corresponding silyl ethers and acetals, respectively, when catalyzed by tris(pentafluorophenyl)borane, (C6 F5 )3 B,115,116 and related boranes.117 This mechanism proposes a pathway in which the first step is the reversible formation of a linear silane-borane adduct that undergoes subsequent nucleophilic attack by the carbonyl compound of the substrate to yield an O-silylated cationic intermediate along with a boron hydride anion.118 The boron hydride ion then transfers a hydride to the carbon center of the O-silylated cation to yield the reduction product and regenerated free borane. A simplified view of the suggested mechanism is shown below (Scheme 1). Similar reaction paths have been proposed for the hydrosilation of enones and silyl ethers119 as well as imines.120
δ+ δ − R3Si—H
R3Si-H + (C6F5)3B + Y
+ SiR3
Y B(C6F5)3 H
Y SiR3
H(C6F5)3B–
Y SiR3
+ (C6F5)3B
Scheme 1
Role of Metal Catalysts A wide variety of metals can effectively catalyze the reduction of multiple bonds by organosilicon hydrides (Eq. 2). No doubt, the function of some of these metals is to serve as Lewis acids by adding to the most electron-rich end of a bond and promoting transfer of hydride to the other center. On the other hand, it is clear that many transition metal complexes function through significantly different and more complex catalytic pathways to promote silane reductions. A common reaction stage suggested for many of the catalytic cycles is the creation of a reactive intermediate having a metal-hydrogen bond that is formed by hydrogen transfer from the silane to the catalytic metal center.116 This reducing center, often with appropriate coordinating ligands, subsequently delivers hydrogen to the substrate and the metal center is freed for additional catalytic cycles. When the catalytic metal ligands are chiral, this process can lead to very high degrees of enantiomeric selectivity in the reduction of prochiral substrates.121 – 125
12
ORGANIC REACTIONS SCOPE AND LIMITATIONS
Reduction of Substituted Alkanes Alcohols to Alkanes. Many alcohols are converted directly into hydrocarbons when treated with acid in the presence of organosilicon hydrides (Eq. 7). The mechanism normally follows the pathway shown in Eq. 1. ROH
"acid" R'3SiH
RH
(Eq. 7)
The reaction generally proceeds cleanly and in high yields (70–100%) when the starting alcohol permits the formation of reasonably stable carbocation intermediates. Alcohols capable of producing carbenium ions spanning a range of stabilities of more than 24 pKR+ units undergo this reduction.26 Depending on the reaction conditions, secondary126 and tertiary127 aliphatic alcohols, secondary and tertiary benzylic alcohols,26,126 some ring-substituted primary benzylic alcohols,26,128,129 and cyclopropylcarbinols130 are reduced to the corresponding alkanes. However, olefinic and rearrangement products can occur from side reactions under these acid conditions.126,131,132 Phenols are not reduced under the same conditions. Almost any organosilicon hydride causes reduction of the cations produced, although the order of reactivity of simple alkyl and aryl-substituted silanes is observed to be triethyl > trioctyl ∼ diethyl > diphenyl ∼ triphenyl.26 A detailed quantitative study of the reactions of organosilicon hydrides with diarylcarbenium ions in dichloromethane at −70◦ indicates a relative reactivity order of R3 SiH > R2 SiH2 > RSiH3 , with alkyl substituent groups generally producing greater reactivity than aryl substituents.61 Use of a deuterated silane yields the corresponding deuterated hydrocarbon (Eq. 8).127,133,66 ROH
"acid" R'3SiD
RD
(Eq. 8)
Normally, only a small stoichiometric excess (2–30 mol%) of silane is necessary to obtain good preparative yields of hydrocarbon products. However, because the capture of carbocation intermediates by silanes is a bimolecular occurrence, in cases where the intermediate may rearrange or undergo other unwanted side reactions such as cationic polymerization, it is sometimes necessary to use a large excess of silane in order to force the reduction to be competitive with alternative reaction pathways. An extreme case that illustrates this is the need for eight equivalents of triethylsilane in the reduction of benzyl alcohol to produce only a 40% yield of toluene; the mass of the remainder of the starting alcohol is found to be consumed in the formation of oligomers by bimolecular Friedel-Crafts-type side reactions that compete with the capture of the carbocations by the silane.129 Both Brønsted and Lewis acids are effective in coordinating with the hydroxyl oxygen to induce heterolysis of the C–O bond and cause formation of the necessary carbocation intermediate. The reactions are frequently conducted
ORGANOSILICON HYDRIDE REDUCTIONS
13
under homogeneous conditions in inert solvents such as dichloromethane or chloroform. Conditions used include the treatment of alcohols with organosilicon hydrides in neat acetic acid,26,29 neat trifluoroacetic acid134 or trifluoroacetic acid/ammonium fluoride135 as well as mixtures of trifluoroacetic acid,26 methanesulfonic acid,126 or triflic (trifluoromethanesulfonic) acid with triflic anhydride126 in dichloromethane or chloroform, mixtures of acetic acid and sulfuric or p-toluenesulfonic acid,134 acetic acid and hydrogen chloride/aluminum chloride,136 and boron trifluoride126 or boron trifluoride etherate in dichloromethane137,133 or chloroform.138 The use of very strong Brønsted acids such as methanesulfonic and triflic acids may cause decomposition of the organosilane through hydrogen production14 and/or cleavage of Si–C bonds139 which compete with the desired reduction of the alcohol.126 These undesirable side reactions may be avoided or reduced by running the reaction at −78◦ .140 Sulfuric acid may cause undesirable oxidations to occur.134 On balance, the most commonly chosen set of conditions for the reduction of alcohols is triethylsilane and trifluoroacetic acid (Et3 SiH/TFA) in dichloromethane solution. The experimental evidence is convincing, at least with benzyl alcohols, that a “free” carbenium ion intermediate devoid of influence from its progenitor is the species that is captured by the non-nucleophilic organosilicon hydride. When optically active 2-phenyl-2-butanol is treated with Et3 SiH/TFA in chloroform, the 2-phenylbutane product is formed with complete racemization.26 When a dichloromethane solution of the same alcohol is treated with trifluoroacetic acid in the presence of enantiomerically enriched 1-naphthylphenylmethylsilane, the 2-phenylbutane product obtained shows a small, but reproducible enantiomeric excess of 2–3%.141 The predominant enantiomer formed in the product is dependent only on the predominant enantiomer of silane used as the reducing agent and is independent of whether one of the pure enantiomers or the racemic alcohol is used as substrate.142 The same stereochemical results are obtained in the hydrocarbon product when the alkene 2-phenyl-1-butene is the precursor to the carbenium ion intermediate (π-route, Eq. 2) instead of the tetrahedral alcohol (σ -route, Eq. 1).142 A similar conclusion is reached from a study of the reduction of optically active 1-phenylethanol to phenylethane-d1 with boron trifluoride etherate and triethylsilane-d1 .133 These experiments illustrate the lack of nucleophilicity or SN 2-like behavior of the organosilicon hydrides in these reactions and presage the stereochemistry expected from such transformations. Primary Alkyl Alcohols. Primary alkyl alcohols do not undergo reduction when treated with Brønsted acids and organosilicon hydrides under usual laboratory conditions.143 This reflects the relative instability of primary alkyl carbenium ions in the condensed phase and the weak intrinsic nucleophilicity of organosilicon hydrides. On the other hand, the combination of excess Et3 SiH and catalytic amounts (5–10 mol%) of (C6 F5 )3 B reduces primary aliphatic alcohols to the alkanes in high yields (Eq. 9), but the reaction stops at the non-reductive silylation of the alcohol with only a single equivalent of the silane.144,145 This type of reaction is thought to proceed via a direct nucleophilic displacement rather than by way of a carbenium ion mechanism.145
14
ORGANIC REACTIONS
Ph
OH
Et3SiH, B(C6F5)3
Ph
CH2Cl2, rt, 20 h
(>95%)
(Eq. 9)
Secondary Alkyl Alcohols. Treatment of secondary alkyl alcohols with trifluoroacetic acid and organosilicon hydrides results only in the formation of the trifluoroacetate esters; no reduction is reported to occur.1,2 Reduction of secondary alkyl alcohols does take place when very strong Lewis acids such as boron trifluoride126,129 or aluminum chloride136,146 are used. For example, treatment of a dichloromethane solution of 2-adamantanol and triethylsilane (1.3 equivalents) with boron trifluoride gas at room temperature for 15 minutes gives upon workup a 98% yield of the hydrocarbon adamantane along with fluorotriethylsilane (Eq. 10).129 OH
Et3SiH
(98%) + Et3SiF
CH2Cl2, BF3
(Eq. 10)
In contrast, when boron trifluoride etherate is substituted for the free boron trifluoride, only a trace of the hydrocarbon is formed, even after weeks of reaction.143 The unique effectiveness of boron trifluoride gas in promoting these reductions is believed to be due to several factors, including the ability of the coordinatively unsaturated boron center to rapidly and tightly coordinate with oxygen centers and to the thermodynamically favorable creation of a Si–F bond.1 A slight pressure of boron trifluoride gas must be maintained over the surface of the solution throughout the reaction because boron trifluoride has only limited solubility in the weakly coordinating dichloromethane solvent. The formation of alkenes and alkene-related polymerization products can seriously reduce the yields of desired alkane products from secondary alcohols, which can undergo elimination reactions. For example, reduction of 2-octanol at 0◦ with boron trifluoride gas in dichloromethane containing 1.2 equivalents of triethylsilane gives only a 58% yield of n-octane after 75 minutes (Eq. 11).129 The remainder of the hydrocarbon mass comprises nonvolatile polymeric material.126 OH n-C6H13
Et3SiH CH2Cl2, BF3
n-C8H18
(58%)
+ polymer
(Eq. 11)
Aluminum chloride, used either as a stoichiometric reagent or as a catalyst with gaseous hydrogen chloride, may be used to promote silane reductions of secondary alkyl alcohols that otherwise resist reduction by the action of weaker acids.136 For example, cyclohexanol is not reduced by organosilicon hydrides in the presence of trifluoroacetic acid in dichloromethane, presumably because of the relative instability and difficult formation of the secondary cyclohexyl carbocation. By contrast, treatment of cyclohexanol with an excess of hydrogen chloride gas in the presence of a three-to-four-fold excess of triethylsilane and 1.5 equivalents of aluminum chloride in anhydrous dichloromethane produces 70% of cyclohexane and 7% of methylcyclopentane after a reaction time of 3.5 hours at
ORGANOSILICON HYDRIDE REDUCTIONS
15
room temperature (Eq. 12).136 The cyclohexane is presumably formed by capture of the secondary cyclohexyl cation, whereas the methylcyclopentane must arise from hydride capture of the more stable tertiary methylcyclopentyl cation formed by rearrangement of the cyclohexyl cation.147,148 Diminishing the amount of aluminum chloride to only 0.5 equivalents results in no reaction after one-half hour and the formation of only 8% of cyclohexane after four hours reaction time. The reaction proceeds slowly in the absence of hydrogen chloride, producing 53% of cyclohexane and 6% of methylcyclopentane after 16.5 hours using two equivalents of aluminum chloride. Et3SiH
(70%)
+
OH HCl, AlCl3
(Eq. 12)
–H2O +
Et3SiH
(7%)
Tertiary Alkyl Alcohols. Tertiary alkyl alcohols generally undergo facile reduction when treated with acids in the presence of organosilicon hydrides.127,136 This comparative ease of reduction reflects the enhanced stability and ease of formation of tertiary alkyl carbenium ions compared with primary and secondary carbenium ions. Thus, treatment of 1-methylcyclohexanol with mixtures of triethylsilane and aluminum chloride in dichloromethane produces near quantitative yields of methylcyclohexane with or without added hydrogen chloride in as little as 30 minutes at room temperature, in contrast to the more vigorous conditions needed for the reduction of the secondary alcohol cyclohexanol.136 Similarly, and in contrast to the behavior of its secondary isomer, 2-adamantanol, 1-adamantanol undergoes smooth, quantitative reduction to adamantane in less than an hour at room temperature in dichloromethane solution containing triethylsilane under the catalysis of either free boron trifluoride129 or boron trifluoride etherate (Eq. 13).143 Et3SiH, CH2Cl2 OH
BF3 or Et2O•BF3
(100%)
(Eq. 13)
Although the synthetic yields of hydrocarbon products obtained from the reduction of tertiary alkyl alcohols are frequently quite high, studies show that the reaction pathways taken by the reactants are not always as direct or straightforward as might be suggested by the structural relationships between reactants and products. For example, preparative-scale treatment of a dichloromethane solution of 3-ethylpentan-3-ol and triphenylsilane (1.2 equivalents) with excess trifluoroacetic acid (1.5 M) at room temperature for 24 hours gives 3-ethylpentane in 78% yield (Eq. 14).127 Under these reaction conditions, the alcohol rapidly
16
ORGANIC REACTIONS
undergoes elimination to 3-ethyl-2-pentene, which is the actual species undergoing reduction. Et
OH
TFA
Et
Et
Et
CH2Cl2
Et
Et
Ph3SiH Et
Et
(Eq. 14)
(78%)
The tertiary alcohol cis,cis,trans-perhydro-9b-phenalenol (7) is converted stereospecifically and in high yield (92%) to trans,trans,trans-perhydrophenalene (10) when treated with either triethylsilane or triphenylsilane and trifluoroacetic acid in dichloromethane (Eq. 15). Studies indicate that the reaction path follows the cation rearrangement 8 → 9 and that the trans trifluoroacetate ester related to cation 9 is an intermediate, which accumulates during the reaction.127 H
OH
H
H
H+
+
H
1,2-H~
H
H
H
R3SiH
H
H
H
(Eq. 15) H 7
+ 9
H 8
H 10 (92%)
The conversion of alcohols directly into the structurally related hydrocarbons by ionic hydrogenation can provide a means of synthesis for compounds that would be extremely difficult or impossible to obtain by other methods. A good example is the synthesis of 2-tert-butyladamantane (12, R = Me). This interesting, highly strained compound may be synthesized in moderate overall yield by a conventional multiple-step route.149 Alternatively, it is obtained in 90% isolated yield upon treatment of a dichloromethane solution of the readily available 2-tert-butyl-2-adamantanol (11, R = Me)150 and one equivalent of either tri-nhexylsilane151,152 or triethylsilane153 with trifluoroacetic acid at room temperature (Eq. 16). OH R
R
R'3SiH
R = Me (90%) R = Ph (96%)
CH2Cl2, TFA 11
(Eq. 16)
12
In a similar fashion, 2-cumyladamantane (12, R = Ph) is formed in nearly quantitative yield upon treatment of the easily synthesized 2-cumyl-2-adamantanol (11, R = Ph)154 with triethylsilane and methanesulfonic acid in dichloromethane at −78◦ .155 The high yield of a single very strained hydrocarbon product in each reaction is quite surprising in view of the very complex interconversions of carbocations known to take place from the alcohol precursors.140,151,152,156 The remarkable chemoselectivity of this reductive technique is demonstrated by the conversion of the functionally rich compound 13 into 14 in 86% yield upon treatment with Et3 SiH/TFA at room temperature for two hours (Eq. 17).157
ORGANOSILICON HYDRIDE REDUCTIONS
HO
O
EtO2C
N H
N
N O
Et3SiH
N
TFA
17
O
(Eq. 17)
(86%) O
EtO2C
N H
13
N
14
Several sterically congested aryldiadamantylmethanols are reduced to atropisomeric diastereomeric mixtures of the corresponding aryldiadamantylmethanes with Et3 SiH/TFA (Eq. 18).158 – 161 Et
Et
Et
Et Et3SiH, TFA, CH2Cl2
Ad Ad HO
O
–10°, rt, 16 h
Et
Et
H + Ad Ad O Ad Ad H
(Eq. 18)
O
(—) 1:1
This reagent combination reduces a tertiary alcohol in the presence of a quinone moiety (Eq. 19).162 Tertiary alcohols are also reduced with the reagent combinations Et3 SiH/MeSO3 H140 and Et3 SiH/AlCl3 /HCl.136 OMe O HO
OMe O Et3SiH, TFA, CH2Cl2 –78° to 0°
CO2Et
CO2Et
O
(Eq. 19)
O (95%)
Cyclopropylcarbinols. Treatment of cyclopropylcarbinols 15 (R = Ph, c-C3 H5 ) with trifluoroacetic acid in dichloromethane leads to the rapid formation of ring-opened 4-substituted 3-butenyl-1-trifluoroacetate esters 16 (Eq. 20).130 Cyclopropylcarbinyl trifluoroacetates are not formed. Ring opening is facilitated by phenyl substituents. Addition of organosilicon hydrides to the reaction mixture favors the formation of cyclopropylmethanes 17 and suppresses the formation of the ring-opened esters.130 R OH R 15 R = c-C3H5 R = Ph
R'3SiH CH2Cl2, TFA
R
O2CCF3 R
R 16
R' = Et R' = Et
R + 17
(Eq. 20)
16 + 17 (—), 16:17 = 1:99 16 + 17 (—), 16:17 = 19:81
Triethylsilane and diethylsilane are somewhat more effective than triphenylsilane at increasing the amount of reduced product 17.130 Yields of 17 in excess of 90% may be obtained. The remainder of the product is butenyl ester 16. Hydrogenolysis of the cyclopropyl rings does not occur under these conditions. A better yield of 17 is obtained when the reaction is carried out at −15◦ than at room
18
ORGANIC REACTIONS
temperature. Under the same set of reaction conditions (dichloromethane, 0.5 M trifluoroacetic acid, 0.5 hour, room temperature), the amount of hydrocarbon product 17 (R = Ph) obtained from diphenylcyclopropylcarbinol changes from 16% with triphenylsilane as the hydride-donating reagent to 45% with triphenylgermane, 85% with triphenylstannane, and 78% with tri-n-butylstannane.24 Benzyl Alcohols. Benzyl alcohols of nearly all kinds undergo reduction when treated with acid in the presence of organosilicon hydrides. The most obvious exception to this is the behavior of benzyl alcohol itself. It resists reduction by the action of trifluoroacetic acid and triethylsilane, even after extended reaction times.26 Reducing systems consisting of triethylsilane and sulfuric acid/acetic acid or p-toluenesulfonic acid/acetic acid mixtures also fail to reduce benzyl alcohol to toluene.134 As previously mentioned, substitution of boron trifluoride for trifluoroacetic acid results in the formation of modest yields of toluene, but only when a very large excess of the silane is used in order to capture the benzyl cation intermediate and suppress Friedel-Crafts oligomerization processes.129,143 Ring-substituted benzyl alcohols sometimes undergo such reduction more effectively than unsubstituted alcohols. For example, treatment of a dichloromethane solution of 2,4,6-trimethylbenzyl alcohol with trifluoroacetic acid and triphenylsilane produces a 41% isolated (89% by GLC) yield of isodurene.26 Treatment of 2-methyl-4,6-di-tert-butylbenzyl alcohol with a three-fold excess of triethylsilane and trifluoroacetic acid in dichloromethane at room temperature gives an 85% yield of 2-methyl-4,6-di-tert-butyltoluene together with 15% of 3,5-di-tert-butyltoluene. The latter is presumably formed by loss of protonated formaldehyde from the C1 ring-protonated substrate.128 Similar treatment of 2,4,6-tri-tert-butylbenzyl alcohol produces a 90% yield of 2,4,6-tri-tertbutyltoluene within one hour (Eq. 21).128 OH t-Bu
Bu-t
R3SiH
t-Bu
Bu-t (90%)
CH2Cl2, TFA
(Eq. 21)
t-Bu
t-Bu
The reduction of 2-(hydroxymethyl)-1,4,6,8-tetramethylazulene to 1,2,4,6,8pentamethylazulene occurs quantitatively upon treatment with triethylsilane and trifluoroacetic acid at 60◦ for 19 hours (Eq. 22).163
HO
Et3SiH TFA, 60°
(100%)
(Eq. 22)
Treatment of either the cis or trans isomer of 4-tert-butyl-1-phenylcyclohexanol with trifluoroacetic acid and one of a variety of organosilicon hydrides in dichloromethane yields a mixture of cis- and trans-4-tert-butyl-1-phenylcyclohexane and the elimination product, 4-tert-butyl-1-phenylcyclohexene
ORGANOSILICON HYDRIDE REDUCTIONS
19
(22–72%) (Eq. 23).26 More elimination product is obtained from the cis than from the trans alcohol. The trans/cis ratio of reduced products is independent of the isomer of starting alcohol used and depends only on the nature of the silane used. This ratio is ca. 1.8 for triorganosilanes (e.g., triethyl, tri-n-octyl, triphenyl) and ca. 4.0 for diorganosilanes (e.g., diethyl, diphenyl) and phenylsilane. The most important factor for the stereoselectivity of product formation seems to be the degree of steric bulk provided by the organic groups bonded to silicon, rather than the electronic nature of the substituents. The smaller the effective steric bulk of the reducing agent, the greater is the trans/cis product ratio.26 Replacement of the silanes with germanes or stannanes as the hydride donors causes a decrease in the amount of elimination product formed so that it becomes a minor product (10–38%).24 The trans/cis ratio of reduced products is ∼2 when triphenylgermane is used, ∼1.4 with triphenylstannane, and ∼0.85 with tri-n-butylstannane.24 Ph OH
t-Bu
Ph
R3SiH CH2Cl2, TFA
t-Bu
R = Et R = Et
cis trans
Ph H + t-Bu
(Eq. 23) (41%) (22%)
(59%) (78%)
Reduction of either the exo or endo isomer of 2-phenyl-2-norbornanol with trifluoroacetic acid and triethylsilane, triphenylsilane, or phenylsilane in dichloromethane gives endo-2-phenylnorbornane quantitatively (Eq. 24).164 The stereospecific formation of only the endo-hydrocarbon can be understood on the basis that only exo approach by organosilicon hydride toward the 2-phenylnorbornyl cation intermediate is kinetically competitive for product formation.164
R3SiH OH Ph
(100%)
CH2Cl2, TFA
(Eq. 24)
Ph
The bornyl system is less subject than the norbornyl system to exclusive exo approach by organosilicon hydrides and related reducing agents because of the steric restraints imposed by the additional methyl groups. Thus, treatment of a dichloromethane solution of p-anisylisoborneol (18) with trifluoroacetic acid and triphenylsilane quantitatively provides the isomeric reduced products p-bornylanisole (19) and p-isobornylanisole (20) in a ratio of 68 : 32 (Eq. 25).24 Replacement of the triphenylsilane with triphenylstannane produces 98% of 19 and 2% of 20. Use of the sterically less demanding phenylsilane gives 19 as the exclusive product. By comparison, trapping of the cation derived from 18 with borohydride gives 87% of 19 and 13% of 20.165
20
ORGANIC REACTIONS
R3SiH OH
+
CH2Cl2, TFA
PMP 18 PMP = 4-MeOC6H4
PMP
PMP R = Ph
(Eq. 25)
19 20 19 + 20 (100%), 19:20 = 68:32
Reductions of tertiary or benzylic alcohols do not always take place as quickly and simply as might be expected. A study of the reduction of 2-methyl-1phenylpropan-1-ol (21, R = OH) and its isomer, 2-methyl-1-phenylpropan-2-ol (22, R = OH), illustrates this observation.166 Both of these alcohols are reduced in high yield (98%) by the action of acid and triphenylsilane to the same hydrocarbon, 2-methyl-1-phenylpropane (21 or 22, R = H). The immediate products formed from either alcohol in a 55% solution of trifluoroacetic acid in nitrobenzene are the trifluoroacetate esters (R = CF3 CO2 ). Surprisingly, at 25◦ in the absence of organosilicon hydride, ester 21 (R = CF3 CO2 ) undergoes complete isomerization to ester 22 (R = CF3 CO2 ) within two hours. Use of triphenylsilaned1 as the reducing agent indicates that alcohol 21 (R = OH) actually produces a mixture of the two isotope-position isomers of the reduction product (21 and 22, R = D), with isomer 22 favored by a factor of 2 to 3 over isomer 21. Similar results are found when the starting alcohol is 22. The conclusion is reached that the species actually captured by the organosilicon hydride consists of a dynamic mixture of the two cations derived from 21 and 22.166 Ph
Ph R
R
21
22
In some instances, treatment of polyfunctional benzylic alcohols with acid in the presence of organosilicon hydrides causes multiple functional group transformations to occur simultaneously. This phenomenon is illustrated by the reduction of the secondary benzylic alcohol function and concomitant loss of the methoxymethyl protecting group of 2-(1-hydroxydecyl)-5-methoxy-1-(methoxymethyleneoxy)naphthalene upon treatment with Et3 SiH/TFA in dichloromethane (Eq. 26).167 O
MeO
OMe CHC9H19-n OH
OH C10H21-n
Et3SiH, TFA
(68%)
CH2Cl2, rt
(Eq. 26)
MeO
An example of an exclusive chemoselective reduction of a benzylic hydroxy function in a polyfunctional compound is seen in the conversion of 23 into 24
ORGANOSILICON HYDRIDE REDUCTIONS
21
in 76% yield using Et3 SiH/TFA (Eq. 27).168 The benzylic hydroxy group in a complex polypeptide derived from lysobactin is selectively reduced with the same reagents (Eq. 28).169 O OBn PMP
OEt CH2Cl2, rt
OH OBn 23
OEt
O OBn
Et3SiH, TFA PMP
(76%)
(Eq. 27)
OBn 24
O OH
H2N O
NH NH
HO
NH O
CO2H H N
H 2N O
O
Ph N H
OH H N
HN
O
O HO
N H
OH O
O
H HN N
O
O
(Eq. 28) NH HN
NH2
H N
Et3SiH, TFA 0°, 1 h
H2N O
O
Ph N H
H N O HO
O N H
(—)
Studies reveal an advantage to using boron trifluoride in dichloromethane at reduced temperatures instead of Brønsted acids in the organosilicon hydride reductions of a number of dialkylbenzyl alcohols.126,129 The use of Brønsted acids may be unsatisfactory under conditions in which the starting alcohol suffers rapid skeletal rearrangement and elimination upon contact with the acid, and also in which the alcohol does not yield a sufficient concentration of the intermediate carbocation when treated with protic acids.126 An example of an alcohol that can undergo rapid skeletal rearrangement is 3,3-dimethyl-2-phenyl-2-butanol (Eq. 29). Attempts to reduce this alcohol in dichloromethane solution with 1-naphthyl(phenyl)methylsilane yield only a mixture of the rearranged elimination products 3,3-dimethyl-2-phenyl-1-butene and 2,3-dimethyl-3-phenyl-1-butene when trifluoroacetic acid or methanesulfonic acid is used. Use of a 1 : 1 triflic acid/triflic anhydride mixture with a 50 mol% excess of the silane gives good yields of the unrearranged reduction product 3,3-dimethyl-2-phenylbutane, but also causes extensive decomposition of the silane.126 In contrast, introduction of boron trifluoride gas into a dichloromethane solution of the alcohol and a 10 mol% excess of the silane
22
ORGANIC REACTIONS
at −60◦ produces 86.5% of the desired, structurally intact hydrocarbon, 3,3dimethyl-2-phenylbutane, along with 13.5% of the methyl-shifted product, 2,3dimethyl-2-phenylbutane, within only six minutes. Clean formation of the fluorosilane related to the organosilicon hydride accompanies the reduction. The workup consists of quenching with solid potassium carbonate followed by addition of water, drying of the dichloromethane solution, and normal product isolation.126 OH Ph
Ph(1-Np)MeSiH
Bu-t
Ph
CH2Cl2, BF3, –65°
Bu-t
+
Ph
(Eq. 29)
(100%) 86.5:13.5
A variety of para-substituted 2-phenyl-2-butanols undergo quick and efficient reductions to the corresponding 2-phenylbutanes when they are dissolved in dichloromethane and a 2–10% excess of phenylmethylneopentylsilane and boron trifluoride is introduced at 0◦ (Eq. 30).126 Several reactions deserve mention. For example, when R = CF3 , use of trifluoroacetic acid produces no hydrocarbon product, even after two hours of reaction time. In contrast, addition of boron trifluoride catalyst provides an 80% yield of product after only two minutes. When R = MeO, both trifluoroacetic acid and boron trifluoride produce a quantitative yield of the hydrocarbon within two minutes. However, when R = NO2 , attempts to promote the reduction with either trifluoroacetic acid or even methanesulfonic acid fail; even after reaction periods of up to eight hours, only recovered starting alcohol is obtained. Use of boron trifluoride provides a quantitative conversion into 2-(p-nitrophenyl)butane after only ten minutes. It is significant that the normally easily reducible nitro group survives these conditions entirely intact.126,129 Triethylsilane may be used as the silane.143 OH Et3SiH CH2Cl2, BF3 R
(100%)
(Eq. 30)
R
Treatment with triethylsilane and boron trifluoride etherate allows a variety of methyl β-hydroxy-β-arylpropionates to be reduced to methyl β-arylpropionates in yields of 85–100% as part of a synthetic sequence leading to the preparation of indanones (Eq. 31).170 Small amounts of dehydration products formed simultaneously are reduced to the methyl β-arylpropionates by mild catalytic hydrogenation.170 OH Ph
CO2Me
Et3SiH BF3•OEt2
Ph
CO2Me
(100%)
(Eq. 31)
Diaryl and triaryl benzylic alcohols generally undergo smooth reduction to the corresponding hydrocarbons. Thus, both diphenyl- and triphenylcarbinol quickly give good to excellent yields of the corresponding substituted methanes when
ORGANOSILICON HYDRIDE REDUCTIONS
23
treated with triphenylsilane or Et3 SiH/trifluoroacetic acid in dichloromethane26 or with triethylsilane and mixtures of either sulfuric or p-toluenesulfonic acids in acetic acid.136 The reductions do not occur with the parent, unsubstituted carbinols using only acetic acid; however, tri-p-anisylcarbinol, 2,2 ,2 ,6,6 ,6 hexamethoxytriphenylcarbinol, 9-phenyl-9H -xanthen-9-ol, 9-p-anisyl-9H xanthen-9-ol,26 and 9-(2,6-dimethoxyphenyl)-1,8-dimethoxy-9H -xanthen-9-ol29 all undergo smooth conversion to the respective hydrocarbons when treated with acetic acid containing triethylsilane. In fact, the use of acetic acid as both solvent and catalyst may be the method of choice in effecting the reductions of very electron-rich benzylic alcohols and those that form acid-labile reduction products. When 2,2 ,2 ,6,6 ,6 -hexamethoxytriphenylcarbinol is treated with Et3 SiH/trifluoroacetic acid in dichloromethane, the reduction goes beyond the triarylmethane stage to produce one equivalent of 2,2 ,6,6 -tetramethoxydiphenylmethane and one equivalent of mdimethoxybenzene.26 These additional products are thought to arise from protonation of one of the electron-rich rings of the initially formed 2,2 ,2 ,6,6 ,6 hexamethoxytriphenylmethane at C1 by the trifluoroacetic acid. Expulsion of a molecule of m-dimethoxybenzene followed by hydride capture of the 2,6,2 ,6 -tetramethoxydiphenylmethyl “daughter” cation formed accounts for the final mixture of products.26 Sesquixanthydrol 25 undergoes reduction to the hydrocarbon only reluctantly, presumably because of the great stability of the sesquixanthydryl cation (1). An early report indicates that the alcohol is able to resist reduction upon treatment with trifluoroacetic acid and excess triethylsilane in dichloromethane for 24 hours and to remain unreduced when dissolved in acetic acid containing triethylsilane.26 A later report indicates formation of the hydrocarbon in 89% yield (Eq. 32).29 O OH O
O H
Et3SiH, HOAc O
reflux, 40 h
O
O
(89%)
(Eq. 32)
25
Intramolecular Friedel-Crafts reactions can sometimes compete with organosilicon hydride reductions of benzylic-type alcohols to cause formation of undesired products. An example is the attempted reduction of alcohol 26 to the corresponding hydrocarbon. When 26 is treated with triethylsilane in trifluoroacetic acid at room temperature for 15 hours, a mixture of the two fluorene isomers 27 and 28 is obtained in a combined yield of 45%. None of the hydrocarbon structurally related to the substrate alcohol 26 is obtained.171 Whether this problem could be circumvented by running the reduction at a lower temperature or with a different acid remains subject to experimentation. Both benzylic and secondary aliphatic alcohols are reduced with the combination of Ph2 ClSiH and a catalytic amount of indium trichloride. This combination
24
ORGANIC REACTIONS F
F
F
OH
OH OH
OH CO2Me
CO2Me
CO2Me
27
26
28
chemoselectively reduces benzyl alcohols in the presence of both ester and halide functions (Eq. 33).172 Ph
Ph2SiHCl, InCl3
CO2R
Ph
CO2R
OH R Et CH2Cl
(Eq. 33)
Conditions ClCH2CH2Cl, 50°, 0.5 h CH2Cl2, rt, 3 h
(68%) (95%)
The combination of excess Et3 SiH and catalytic amounts (5–10 mol%) of (C6 F5 )3 B reduces benzylic alcohols to the hydrocarbons (Eq. 34), although the reaction stops at the non-reductive simple silylation of the alcohol with only a single equivalent of the silane.144,145 OH Ph
Et3SiH, (C6F5)3B CH2Cl2, rt, 20 h
Ph
Ph
Ph
(Eq. 34)
(98%)
Allyl Alcohols. Secondary cyclic allylic alcohols are reduced with the combination of Et3 SiH and ethereal LiClO4 , even in the presence of a tertiary alcohol (Eq. 35) or ketal function.173 Primary allylic alcohols do not undergo deoxygenation under similar conditions.173 OH
HO
Et3SiH, LiClO4 Et2O, rt, 16 h
OH
(Eq. 35)
(52%)
Treatment of 1-[2-(2-methoxy-5-isopropylphenyl)-1-hydroxyethyl]-2,6,6-trimethylcyclohexene with triethylsilane and boron trifluoride etherate in dichloromethane at −10◦ leads to its reduction to 2-(2,6,6-trimethyl-1-cyclohexenyl)-1(2-methoxy-5-isopropylphenyl)ethane in 69% yield (Eq. 36).174 OMe
OMe Et3SiH, CH2Cl2
OH
Et2O•BF3, –10°
(69%)
(Eq. 36)
Metal-Complexed Alcohols. It is well known that carbocations are frequently stabilized when organotransition metal centers are present in adjacent portions of
ORGANOSILICON HYDRIDE REDUCTIONS
25
the molecule.175 – 177 It is thus not surprising that alcohols possessing such centers are prone to undergo facile reduction upon treatment with acids and organosilicon hydrides. Perhaps it is more surprising that the coordinated metal centers survive the reduction conditions so well. Methylferrocenylcarbinols bearing several functional groups (R = H, Cl, CO2 Me, CN) on the distal C5 ring undergo reduction to the corresponding ethylferrocenes when treated with an excess of Et3 SiH/TFA in acetic acid solution at 20◦ (Eq. 37).178 The yields of reduced product are no less than 85% within three hours, except when R = CN. Then the conversion into the ethylferrocene is only 55% complete after 20 hours of reaction time, reflecting the destabilizing effect of the cyano group on the intermediate carbocation. In a similar fashion, symmetrically disubstituted ferrocenylcarbinols undergo facile double deoxidative reduction in yields of more than 80% within three hours at 20◦ when dissolved in trifluoroacetic acid and treated with two equivalents of triethylsilane (Eq. 38).179 The “half-sandwich” cyclopentadienylmanganese tricarbonyl (cymantrene) carbinol undergoes reduction in a similar way to that of its ferrocenylcarbinol analogs (Eq. 39).180
OH
Fe R
Et3SiH, TFA HOAc, 20°
(55-95%)
Fe R
(Eq. 37)
R = H, Cl, CO2Me, CN R Fe
R OH
R Et3SiH, TFA Fe
R
(83-90%)
OH
(Eq. 38)
R = H, Me, CH2CN Et Mn(CO)3
Et3SiH, TFA OH
Et Mn(CO)3
(92%)
(Eq. 39)
Highly diasteroselective and chemoselective reductions may be performed on the hydroxy functions of (η6 -arene)-tricarbonylchromium complexes. Treatment of the chromium-complexed benzylic alcohol 29 with triethylsilane and boron trifluoride etherate in dichloromethane at −78◦ to 0◦ gives only diastereomer 30 in 75% yield (Eq. 40).181 In a similar fashion, treatment of the complexed exoallyl-endo-benzylic alcohol 31 with an excess of Et3 SiH/TFA in dichloromethane at room temperature under nitrogen produces only the endo-allyl product 32 in 92% yield after 1.5 hours (Eq. 41). It is noteworthy that no reduction of the isolated double bond occurs.182
26
ORGANIC REACTIONS OH OBn
OBn Et3SiH, CH2Cl2 BF3•OEt2, –78° to 0°
OMe
(CO)3Cr
(CO)3Cr
29
(75%)
(Eq. 40)
(92%)
(Eq. 41)
OMe 30
(CO)3Cr
Et3SiH, CH2Cl2 OH
(CO)3Cr
TFA
31
32
Treatment of α-hydroxyalkylidynetricobalt nonacarbonyl complexes of type 33 with strong acids produces the related highly stabilized carbocations 34.183 As expected, heating a tetrahydrofuran solution of the methyl compound (33, R = Me) with trifluoroacetic acid and triethylsilane at reflux for four hours produces the related hydrocarbon complex (35, R = Me) in 72% yield. Somewhat surprising, however, is the report that the hexafluorophosphate salt of the phenylsubstituted carbocation (34, R = Ph, X− = PF6 − ), preformed by treatment of the corresponding alcohol with hexafluorophosphoric acid, produces only 7% of the related hydrocarbon complex when exposed to triethylsilane in tetrahydrofuran for 1.5 hours at room temperature. This lower yield of hydrocarbon complex from the phenyl system compared with the methyl analog is probably a reflection of the greater stability and lower reactivity of the intermediate cation. OH (CO)9Co3CC H R 33
H + – (CO)9Co3CHC X R 34
(CO)9Co3CCH2R 35
33–35 R = Me, Ph
Polyfunctional Hydroxy Compounds. Different classes of alcohols can serve as the precursors to carbocations that have different stabilities and different degrees of ease of formation. It is thus no surprise that selective acid-catalyzed organosilicon hydride reductions of alcohols of one type may be effected in the presence of others if the proper reaction conditions are employed. For example, either tertiary or secondary benzylic hydroxy groups may be replaced by hydrogen without affecting primary aliphatic-type hydroxy groups in the same molecule when boron trifluoride etherate and triethylsilane are used.137 This Et3 SiH/BF3 • OEt2 reagent combination is also selective for a benzylic alcohol over an aliphatic alcohol function.137 Treatment of 1,1-diphenylpropane-1,3-diol with two equivalents each of boron trifluoride etherate and triethylsilane in dichloromethane at 0◦ gives a 90% yield of 3,3-diphenylpropan-1-ol after 30 minutes (Eq. 42). Replacement of the terminal CH2 OH group by a CO2 Et group and similar treatment produces a product mixture containing 50% of the reduced product and 18% of the corresponding
ORGANOSILICON HYDRIDE REDUCTIONS
27
alkene elimination product. The carboethoxy group is unaffected by these reduction conditions.137 Ph
OH
Ph
Ph
Et3SiH, CH2Cl2
(Eq. 42)
(90%)
BF3•OEt2, 0°, 0.5 h
OH
OH Ph
The secondary benzylic alcohol 1-phenylethan-1,2-diol requires 20 hours of treatment at room temperature to produce a 64% yield of 2-phenylethanol (Eq. 43).137 Under the same conditions, methyl mandelate fails to undergo reduction, presumably because of the greater carbocation-destabilizing effect of a neighboring carboalkoxy compared to a hydroxymethyl group (Eq. 43).137 OH Ph
Et3SiH, BF3•OEt2 Ph
rt, 20 h
R
(64%)
R
(Eq. 43)
R CH2OH CO2Me
(64%) (0%)
Triethylsilane/boron trifluoride etherate in chloroform at room temperature reduces only the benzylic 12-hydroxy group of the polyfunctional compound 36 to form (±)-homochelidonine 37 in 92% yield (Eq. 44).138 OH HO H
HO H
O O N
MeO
Et3SiH, CHCl3
H Me
O O
BF3•OEt2
H N Me
MeO
(92%)
OMe
OMe 36
37
(Eq. 44)
It is possible to effect reduction of tertiary benzylic hydroxy functions in the presence of primary halogens. Treatment of 1,1-diphenyl-1-hydroxy-2haloethanes in chloroform with a slight excess of triethylsilane and a 9- to 10-fold excess of trifluoroacetic acid yields the corresponding 2,2-diphenyl-1-haloethanes (Eq. 45). The yield of the chloride is 77% after one hour at −15◦ , whereas that of the bromide is 66% following one hour at 0◦ .184 X OH Ph
Ph
Et3SiH, CHCl3 TFA
X Ph
Ph
X Cl Br
(77%) (66%)
(Eq. 45)
Alkyl Halides and Triflates to Alkanes. The normal requirements for conversion of alkyl halides (and triflates) to alkanes using organosilicon hydrides are essentially the same as those needed for the reduction of the corresponding alcohols, namely, the substrates must generally be able to serve as precursors to
28
ORGANIC REACTIONS
carbocations that may be captured by the hydride. The reduction of alkyl halides has been accomplished with triethylsilane/aluminum chloride. Substrates that undergo reduction under these conditions include primary alkyl halides,146,185,186 secondary alkyl halides,146,187,188 gem-dihalides,189 vicinal dihalides,189 and tertiary alkyl halides.187,188 As expected, haloarenes generally do not undergo such reductions, even under vigorous conditions.146,190 An exception to the need for carbocation formation is found when the silyl hydride functional group is part of a valence-expanded hydrosiliconate species. For example, potassium tetraethoxyhydridosilicate104 is capable of reducing primary alkyl and benzylic bromides and chlorides directly to the corresponding hydrocarbons without the need for additional catalysis (Eq. 46).95 The reaction is not a simple nucleophilic displacement of hydride for halide, however, since dimers can be formed as part of the reaction product mixture. In addition, when 6bromo-1-hexene is used as the substrate, 4.4% of methylcyclopentane is obtained along with 63% of 1-hexene product.95 The presence of the ring-closed product is suggestive of the operation of single-electron transfer (SET) processes.191 [(EtO)4SiH]– K+ + RX
THF, 48 h RH + RR + Si(OEt)4
(Eq. 46)
R = primary alkyl, benzyl
Alkyl Halides. Commonly, reductions with liquid silanes and liquid alkyl halides do not require the use of a solvent.186 When the alkyl halide is a solid, either pentane186 or dichloromethane may be used as solvent.192 No significant difference in reactivities is observed between alkyl chloride and bromide substrates,186 but allyl halides are more reactive than 2-halopropanes, which, in turn, are more reactive than 1-halopropanes.190,146 With halides having a strong propensity to undergo ionization, such as trityl halides, reductions may occur in the absence of added Lewis acids.29,54 Otherwise, the presence of Lewis acids is required. Catalytic amounts of aluminum bromide and aluminum chloride seem to be equally effective unless there are other Lewis base centers such as oxygen in the molecule to compete with the halogen for complexation with the Lewis acid.192 Then it is necessary to add more than one equivalent of the Lewis acid to effect reduction of the carbon-halogen function.136,146 Skeletal rearrangements may occur during these reductions, as in the reduction of bromocycloheptane (Eq. 47).146,185 Br Et3SiH, AlCl3
+
HCl (39%)
(Eq. 47) (26%)
In contrast to the behavior of primary alcohols, which resist reduction by organosilicon hydrides even in the presence of very strong acids, primary halo alkanes, including methyl iodide and ethyl bromide,186 undergo reduction when treated with aluminum chloride and organosilicon hydrides.146,185,186 Slow addition of a catalytic amount of aluminum chloride to a nearly equimolar
ORGANOSILICON HYDRIDE REDUCTIONS
29
mixture of 1-chlorohexane and triethylsilane produces a vigorous reaction that, after 28 hours and simple distillation, gives a 57% yield of n-hexane and an 88% yield of chlorotriethylsilane (Eq. 48).185 Similar treatment of 2,2-dimethyl1-chloropropane gives 2-methylbutane in 37% yield (Eq. 49), whereas treatment of 3,3-dimethyl-1-chlorobutane gives a 50% yield of 2-methylbutane (Eq. 50).185 Polymeric hydrocarbon by-products accompany the products of the latter two reactions. The structures of the products are clear evidence of the occurrence of 1,2-alkyl shifts leading to more stable carbocationic intermediates. Cl
Et3SiH
(57%)
AlCl3 Et3SiH
Cl
AlCl3 Et3SiH
Cl
AlCl3
(Eq. 48)
(37%)
(Eq. 49)
(50%)
(Eq. 50)
The use of a deuterium-labeled organosilicon hydride and location of the deuterium isotope in the reduced product shows that 1,2-hydride shifts also occur. Thus, reduction of 1-bromohexane with triethylsilane-d1 yields hexane with all of the deuterium at C2 (Eq. 51); similar treatment of cyclohexylmethyl bromide produces methylcyclohexane-1-d1 (Eq. 52).186 Et3SiD Br
AlCl3
Br
D
(—)
(Eq. 51)
D Et3SiD
(Eq. 52)
(—)
AlCl3
Trialkylsilanes are generally more effective than dialkyl- or monoalkylsilanes in minimizing isomerizations. The reduction of 2-bromododecane to dodecane proceeds under aluminum chloride catalysis in 82% yield using n-butylsilane and in 87% yield with tri-n-butylsilane.186 However, similar treatment of bromocycloheptane with triethylsilane yields a mixture of 39% cycloheptane and 26% methylcyclohexane. The same substrate yields 65% methylcyclohexane and less than 1% cycloheptane when n-butylsilane is the reducing agent.186 Total reduction of unbranched open-chain and cyclic derivatives of dichloro and dibromo alkanes occurs at room temperature within 30 minutes in dichloromethane solutions containing ca. 2.5 equivalents of triethylsilane and ca. 0.25 equivalents of aluminum chloride.189 The reaction occurs equally well with geminal, vicinal, and ω-dihalo alkanes. For example, 1,5-dibromopentane gives n-pentane in 85% yield when treated in this way (Eq. 53).189 Br
Br
Et3SiH CH2Cl2, AlCl3
(85%)
(Eq. 53)
30
ORGANIC REACTIONS
Chlorocyclohexane is converted into cyclohexane in dichloromethane using ethyldichlorosilane as reducing agent.192 The product yield is 40% with 25 mol% aluminum chloride and 45% with aluminum bromide. 1-Chloro-1-methylcyclohexane gives a 94% yield of methylcyclohexane using aluminum chloride and a 92% yield with aluminum bromide. Ethyldichlorosilane is superior as a hydride donor to either cumene or dicumylmethane.192 2-Bromoadamantane and 1-bromoadamantane are reduced to adamantane in yields of 84% and 79%, respectively, when treated with triethylsilane and catalytic amounts of aluminum chloride.186 Similar treatment of benzhydryl chloride and exo-2-bromonorbornane gives the related hydrocarbons in yields of 100% and 96%, respectively.186 In contrast, 2-bromo-1-phenylpropane gives only a 43% yield of 1-phenylpropane; the remainder consists of Friedel-Crafts alkylation products.186 Some alkyl halides resist reduction by this method, even when forcing conditions are employed. These include p-nitrobenzyl bromide, 3-bromopropanenitrile, and 5-bromopentanenitrile.186 The reduction of 4-chloro-4-methyltetrahydropyran with triethylsilane requires more than a catalytic amount of aluminum chloride. No 4-methyltetrahydropyran is obtained after 20 hours at room temperature even when 0.75 equivalents of the catalyst is used, but a 92% yield is obtained after only 30 minutes when two equivalents of catalyst and three equivalents of triethylsilane are used.136,146 This is presumably a result of the ability of the Lewis acid to coordinate at the ring oxygen as well as at the chlorine. The introduction of alkyl groups at C2 appears to introduce enough steric hindrance near the ring oxygen to enable less than one equivalent of aluminum chloride to effect reduction, but also makes the products unstable to the reaction conditions so that the synthetic yields decline compared with the unsubstituted substrate.136 Dichloromethane solutions of some sterically congested benzyl chlorides and triethylsilane need only the addition of excess trifluoroacetic acid to promote rapid conversion of the chlorides to the related hydrocarbons.128 Thus 2,4,6trimethylbenzyl chloride produces a 79% yield of isodurene at room temperature after 2.5 hours, 2-methyl-4,6-di-tert-butylbenzyl chloride gives 50% 1, 2-dimethyl-4,6-di-tert-butylbenzene after 40 minutes at reflux, and 2,4,6-tert-butylbenzyl chloride gives a 100% yield of 2,4,6-tri-tert-butyltoluene within 17 minutes at reflux (Eq. 54). The unsubstituted parent benzyl chloride remains unreacted under these conditions even after 30 days.128
R1
R1 Cl
R2
Et3SiH, CH2Cl2 TFA
R2
R2 R1
R2
Me Me t-Bu
Me t-Bu t-Bu
(79%) (50%) (100%)
R2
(Eq. 54)
ORGANOSILICON HYDRIDE REDUCTIONS
31
It is clear that the ionizing power of the solvent used is important in many of these reductions. When 2,4,6-trimethylbenzyl chloride is heated with diphenylsilane in nitrobenzene at temperatures as high as 130◦ , no isodurene is formed.193 Not unexpectedly, the same lack of reactivity is reported for a series of benzyl fluorides, chlorides, and bromides substituted in the para position with nitro or methyl groups or hydrogen when they are heated in nitrobenzene solutions with triethylsilane, triethoxysilane, or diphenylsilane.193 The combination of boron trifluoride etherate and triethylsilane can cause the reduction of tertiary fluoride centers even in polyfunctional compounds (Eq. 55).194 O Ph
O O
Ph
Et3SiH, BF3•OEt2
O
(100%)
CH2Cl2, –20°, 8 h
F
(Eq. 55)
Alkyl iodides, benzyl chlorides, benzyl bromides, and adamantyl bromides and iodides undergo reduction with triethylsilane/palladium chloride.195 The reduction of a β-chloro ether occurs in excellent yield with this system (Eq. 56).195 MeO
Cl
O
Et3SiH, PdCl2
MeO
rt, 10 min
(>95%)
O
(Eq. 56)
Allyl Halides. Reduction of a polyfunctional allyl chloride occurs without rearrangement and without reduction of the tosylate using Ph2 SiH2 /ZnCl2 / Pd(PPh3 )4 (Eq. 57).196 Ph2SiH2, ZnCl2, Pd(PPh3)4 SO2Tol Cl
SO2Tol
THF, rt, 12 h, 50°, 6 h
(Eq. 57)
(58%)
α-Halocarbonyl Compounds. The reduction of α-chloro and α-bromo ketones and esters has been accomplished with combinations of PhSiH3 / Mo(CO)6 ,197 Ph2 SiH2 /ZnCl2 /Pd(PPh3 )4 ,197 Ph2 SiH2 /Pd(OAc)2 ,197 and Et3 SiH/ PdCl2 ,195 with the first reagent combination giving the best results.197 One example of an α-chloro amide reduction is reported.198 2-Bromopropiophenone is reduced to propionic acid with polymethylhydrosiloxane (PMHS, 38), an inexpensive industrial commodity, and Pd(PPh3 )4 in 35% yield.199 This reagent combination also reduces α-halo ketones in high yields (Eq. 58).199 O
O Br
PMHS, Pd(PPh3)4, Bn3N MeCN/Me2SO (1:1), 110°, 3 h
Me3Si O
H Si O SiMe3 Me n
38
(80%)
(Eq. 58)
32
ORGANIC REACTIONS
Vinyl and Aryl Halides and Triflates. The organosilane reduction of aryl halides is possible in high yields with triethylsilane and palladium chloride.195 The reaction is equally successful with aryl chlorides, bromides, and iodides. Aryl bromides and iodides, but not chlorides, are reduced with PMHS/Pd(PPh3 )4 in moderate to excellent yields.199 This system also reduces vinyl bromides.199 p-Chlorobenzophenone is reduced to benzophenone with sym-tetramethyldisiloxane and Ni/C in excellent yield (Eq. 59).200 There is a report of the organosilane reduction of aryl and vinyl triflates in very high yields with the combination of Et3 SiH/Pd(OAc)2 /dppp (1,3-bis(diphenylphosphino)propane) (Eq. 60).201 O
O HMe2SiOSiMe2H, 10% Ni/C
(96%)
PPh3, dioxane, reflux, 15 h
(Eq. 59)
Cl N
CF3
n-C10H21
OTf N
CF3
Et3SiH, Pd(OAc)2 dppp, DMF, 60°, 3 d
N
CF3
N
CF3 (95%)
n-C10H21
(Eq. 60) Reduction of Unsaturated Hydrocarbons Alkenes to Alkanes. The “ionic hydrogenation” of many compounds containing carbon-carbon double bonds is effected with the aid of strong acids and organosilicon hydrides following the π-route outlined in Eq. 2. A number of factors are important to the successful application of this method. These include the degree and type of substituents located around the double bond as well as the nature and concentrations of the acid and the organosilicon hydride and the reaction conditions that are employed. The most common reaction conditions for alkene reductions use excess trifluoroacetic acid and triethylsilane either neat202 – 204 or in an inert solvent such as nitrobenzene,134 2-nitropropane,205 carbon tetrachloride,206 chloroform,207 or dichloromethane.127,164 Reaction temperatures from −78◦ to well over 100◦ are reported. Ambient or ice-bath temperatures are most commonly used, but variations of these conditions abound. Among other silicon hydrides reported are n-butylsilane, diethylsilane, triisopentylsilane, tricyclopentylsilane, triphenylsilane, tri-sec-butylsilane, di-tertbutylsilane, di-tert-butylmethylsilane, tri-tert-butylsilane,204 phenylsilane, diethylmethylsilane,202 diphenylsilane,134,208,209 dichloroethylsilane,192 PMHS,77 and polyethylhydrosiloxane.207 Acids that are used in addition to trifluoroacetic acid include trifluoroacetic acid with added sulfuric acid203 or boron trifluoride etherate,210,211 perfluorobutyric acid,212 hydrogen chloride/aluminum chloride,136,146,213 perchloric acid in chloroform,214 p-toluenesulfonic acid alone134 or with aluminum bromide or aluminum chloride,192 concentrated sulfuric acid in two-phase systems with dichloromethane, alcohol, or ether solvents,209,215 trifluoromethanesulfonic acid,216 chlorodifluoroacetic acid,134 and the monohydrate of boron trifluoride
ORGANOSILICON HYDRIDE REDUCTIONS
33
(BF3 •OH2 ).217 The use of a sulfonated phenol-formaldehyde polymer in conjunction with formic acid is also reported.208 Acids that are ineffective include phosphoric,208 trichloroacetic, dichloroacetic, and acetic acids.134 It is reported that addition of lithium perchlorate to the reaction mixture improves product yields.193,205 Other organosilane/acid reagent combinations that are used in the reduction of olefins to alkanes include Et3 SiH/NH4 F/TFA,135 Et3 SiH/HClO4 ,214 Et3 SiH/ TiCl4 ,218 PMHS/Pd-nanocomposite,219 Et3 SiH/TFA/HClO4 ,205 Et3 SiH/PdCl2 ,220 polyethylhydrogensiloxane (PEHS)/TFA,207 Et3 SiH/TMSOTf,216 and Et3 SiH/ HCO2 H.208 The triethylsilane/trifluoroacetic acid reagent system reduces alkenes to alkanes in poor to excellent yields depending largely on the ability of the alkene to form carbocations upon protonation. Under these conditions the more substituted olefins are reduced in better yields and styrene double bonds are reduced in high yields.127,202,207,221 – 228 The reduction of 1,2-dimethylcyclohexene with this reagent gives a mixture of cis- and trans-1,2-dimethylcyclohexane.229 The formation of the trifluoroacetate esters is a side reaction.205,230 Potential problems associated with double bond reduction by this method may be understood in terms of Eq. 61. Protonation of the double bond leads to the formation of the more stable carbocation. This carbocation may rearrange by a first-order process or react competitively with either indigenous nucleophiles or added silicon hydride by second-order processes. If strong nucleophiles such as those associated with weak Brønsted acids are present, then the limited degree of reversibility of carbocation regeneration following nucleophilic capture may lead to diversion of the desired reduction products to unwanted nucleophilic substitution products.209 Another problem exists if bimolecular polymerization reactions compete with carbocation capture by organosilicon hydrides because of the proximity of carbocations and unprotonated alkene substrate. When this occurs, yields of reduced product suffer. The yields of hydrocarbons from alkenes are, in fact, frequently lower than those of the same products derived from the corresponding alcohols because of this problem.134,142
H X
(Eq. 61) + X–
HX H
R3SiH H H
When trifluoroacetic acid is used as the source of protons, it is known that rapid formation of trifluoroacetate esters precedes reduction to hydrocarbons.134,204,206 Use of acetic acid in place of trifluoroacetic acid, for example, would be expected to fail to produce good conversion to reduced product because of the combination of decreased acidity and increased nucleophilicity of acetic acid relative to
34
ORGANIC REACTIONS
trifluoroacetic acid as well as its weaker ionizing power as a solvent. This is consistent with experimental observations.134,209 The relative stability of the carbenium ion resulting from double bond protonation is a controlling factor in the limitation of this method of hydrogenation. On a practical level, only alkenes that can produce carbenium ions at least as stable as tertiary aliphatic ones undergo reduction to alkanes in useful yields. This distinction serves as a basis for selectivity of reduction. Under essentially every set of conditions reported, 1-methylcyclohexene, which forms a tertiary aliphatic carbenium ion upon protonation, undergoes reduction to methylcyclohexane in good to excellent yields, whereas cyclohexene, which can only form a secondary aliphatic carbenium ion intermediate upon protonation, does not normally undergo reduction. Indeed, treatment of an equimolar mixture of cyclohexene and 1-methylcyclohexene with two equivalents of triethylsilane and four equivalents of trifluoroacetic acid at 50◦ gives, after 10 hours, a 70% yield of methylcyclohexane together with completely recovered, unreacted cyclohexene.231 An exception is reported when the reactions are conducted using a twofold excess of dichloroethylsilane with equal equivalents of either aluminum chloride or aluminum bromide and p-toluenesulfonic acid at 40◦ for two hours in dichloromethane. Under these conditions, 1-methylcyclohexene affords methylcyclohexane in 65–75% yield, whereas cyclohexene gives cyclohexane in 17–23% yield.192 The use of deuterated organosilicon hydrides in conjunction with proton acids permits the synthesis of site-specific deuterium-labeled compounds.59,126,221 Under such conditions, the deuterium atom in the final product is located at the charge center of the ultimate carbocation intermediate (Eq. 62). With the proper choice of a deuterated acid and organosilicon hydride, it may be possible to use ionic hydrogenation in a versatile manner to give products with a single deuterium at either carbon of the original double bond, or with deuterium atoms at both carbon centers.127 +
+ X–
HX H
R3SiD
(Eq. 62) H D
Monosubstituted Alkenes. Simple unbranched terminal alkenes that have only alkyl substituents, such as 1-hexene,203 1-octene,209 or allylcyclohexane230 do not undergo reduction in the presence of organosilicon hydrides and strong acids, even under extreme conditions.1,2 For example, when 1-hexene is heated in a sealed ampoule at 140◦ for 10 hours with triethylsilane and excess trifluoroacetic acid, only a trace of hexane is detected.203 A somewhat surprising exception to this pattern is the formation of ethylcyclohexane in 20% yield upon treatment of vinylcyclohexane with trifluoroacetic acid and triethylsilane.230 Protonation of the terminal carbon is thought to initiate a 1,2-hydride shift that leads to the formation of the tertiary 1-ethyl-1-cyclohexyl cation.230 On the other hand, if the single substituent can stabilize an adjacent carbocation center following protonation of the alkene, then reduction may occur.
ORGANOSILICON HYDRIDE REDUCTIONS
35
Styrene is reported to undergo reduction upon treatment with trifluoroacetic acid and triethylsilane,203 although competing polymerization reactions limit the yield of ethylbenzene to only 30% (Eq. 63).70 Vinylcyclopropane is reduced to ethylcyclopropane within 30 minutes under similar conditions (Eq. 64).232 It is important to note that the cyclopropane ring of ethylcyclopropane can be opened under these reaction conditions, albeit with longer reaction times, to give some trans2-pentene in the final reaction mixture.233 Et3SiH
(30%)
(Eq. 63)
(100%)
(Eq. 64)
TFA Et3SiH TFA, rt
Examples of the behavior of other substituted vinyl substrates upon exposure to the action of trifluoroacetic acid and triethylsilane are known. For example, n-butyl vinyl ether, when reacted at 50◦ for 10 hours, gives n-butyl ethyl ether in 80% yield (Eq. 65).234 In contrast, n-butyl vinyl thioether gives only a 5% yield of n-butyl ethyl sulfide product after 2 hours and 15% after 20 hours of reaction.234 It is suggested that this low reactvity is the result of the formation of a very stable sulfur-bridged carbocation intermediate that resists attack by the organosilicon hydride (Eq. 66). Et3SiH
O
S
H+
+S
Et3SiH
(Eq. 65)
(80%)
O
TFA
S
(15%)
(Eq. 66)
20 h
Attempted reduction of vinyl acetate yields a mixture containing 8% ethyl acetate and 3% ethyl trifluoroacetate after 10 hours. The amounts of the two esters change to 13% and 12%, respectively, at reaction times beyond 60 hours.234 Vinyl trifluoroacetate does not undergo reduction under these conditions, even after 75 hours.234 Treatment of N -vinyl-3-methyl-6-pyridazone with excess trifluoroacetic acid and triethylsilane at 65◦ for 25 hours yields 67% of the reduced product N -ethyl3-methyl-6-pyridazone (Eq. 67).235 It is noteworthy that only the vinyl group in this compound undergoes reduction under these conditions, and not the ring or carbonyl sites. Examination of a solution of the starting N -vinyl-3-methyl6-pyridazone in neat trifluoroacetic acid by 1 H NMR spectroscopy shows the existence of the trifluoroacetate ester expected from the carbocation formed by protonation of the vinyl group at the terminal carbon. It is of interest that a similar compound, N -allyl-3-methyl-6-pyridazone, is inert under these conditions (Eq. 68). This reflects the differences of the relative stabilities of the carbocations formed upon protonation of the C=C groups in each reaction.
36
ORGANIC REACTIONS
N N
N N
Et3SiH TFA
O
(67%)
(Eq. 67)
O
N N
Et3SiH
(Eq. 68)
no reaction
TFA
O
Disubstituted Alkenes. Simple 1,2-disubstituted alkenes such as 2-octene or cyclohexene, which produce only secondary aliphatic carbocation reaction intermediates, do not undergo reduction upon treatment with a Brønsted acid and an organosilicon hydride. Even when extreme conditions are employed, only traces of reduction products are detected.192,203,207 – 210,214 An exception is the report that 4-methyl-2-pentene forms 2-methylpentane in 70% yield when heated to 50◦ for 20 hours with a mixture of Et3 SiH/TFA containing a catalytic amount of sulfuric acid. It is believed that 4-methyl-2-pentene is isomerized to 2-methyl-2-pentene prior to reduction.203 Unlike cyclohexene, its oxa analog, 3,4-dihydro-2H -pyran, undergoes facile reduction to tetrahydropyran in yields ranging from 70 to 92% when treated with a slight excess of triethylsilane and an excess of either trifluoroacetic acid or a combination of hydrogen chloride and aluminum chloride (Eq. 69).146 This difference in behavior can be understood in terms of the accessibility of the resonance-stabilized oxonium ion intermediate formed upon protonation. Et3SiH
HX
(70-92%) O
O X– +
O
(Eq. 69)
The behavior of the isomeric dihydronaphthalenes emphasizes the importance of the relative stabilities of carbocation intermediates in ionic hydrogenations. Treatment of 1,2-dihydronaphthalene with Et3 SiH/TFA at 50–60◦ gives a 90% yield of tetralin after one hour. Under the same conditions, the 1,4dihydronaphthalene isomer gives less than 5% of tetralin after 70 hours.224 This difference in reactivity is clearly related to the relatively accessible benzylic cation formed upon protonation of the 1,2-isomer compared to the less stable secondary cation formed from the 1,4-isomer.224 The behavior of members of the bicyclo[2.2.1]heptene family is also different from that of other common 1,2-disubstituted alkenes.230 The parent bicyclo[2.2.1]heptene gives bicyclo[2.2.1]heptane in only 3.5% yield when it is treated with Et3 SiH/TFA. The major product is reported to be a 2-bicyclo[2.2.1]heptyl trifluoroacetate of unspecified configuration (Eq. 70).230 The carbocation intermediate is presumably the 2-norbornyl cation. Addition of small amounts of boron trifluoride etherate to the reaction mixture causes the yield of hydrocarbon product to rise to 22% after a reaction time of 24 hours at room temperature. Further
ORGANOSILICON HYDRIDE REDUCTIONS
37
exposure of the reaction mixture to the reaction conditions does not result in additional hydrocarbon formation from the ester. Et3SiH
+
O2CCF3
TFA
(Eq. 70)
(3.5-22%)
A mixture of exo- and endo-isomers of 5-methylbicylo[2.2.1]hept-2-ene is hydrogenated with the aid of five equivalents of triethylsilane and 13.1 equivalents of trifluoroacetic acid to produce a 45% yield of endo-2-methylbicylo[2.2.1] heptane (Eq. 71). The same product is formed in 37% yield after only five minutes. The remainder of the reaction products is a mixture of three isomeric secondary exo-methylbicylo[2.2.1]heptyl trifluoroacetates that remains inert to the reaction conditions. Use of triethylsilane-1-d1 gives the endo-2-methylbicylo[2.2.1]heptane product with an exo-deuterium at the tertiary carbon position shared with the methyl group. This result reflects the nature of the internal carbocation rearrangements that precede capture by the silane.230 Et3SiH
H(D)
+
TFA, rt, 24 h (45%)
(Eq. 71) (55%)
O2CCF3
Alkenes with a 1,1-disubstitution pattern form tertiary carbocations upon treatment with a Brønsted acid. Consequently, such compounds are often easily reduced (Eq. 72). An example of this is the formation of 2-methylpentane in 93% yield after only 5 minutes when a dichloromethane solution of 2-methyl1-pentene and 1.4 equivalents of triethylsilane is treated with 1.4 equivalents of trifluoromethanesulfonic acid at −75◦ .216 Similar treatment of 2,3-dimethyl-1butene gives a 96% yield of 2,3-dimethylbutane.216 CF3SO3H R R = alkyl
Et3SiH, –75°
R R = n-Pr (93%) R = i-Pr (96%)
(Eq. 72)
Use of deuterated silane and/or acid with this method leads to site-specific deuterium incorporation in the reduced products. Thus, treatment of 2-methyl-1pentene with one equivalent of deuterated triethylsilane and two equivalents of trifluoroacetic acid at 50◦ for 24 hours gives 2-methylpentane-2-d1 in 90% yield (Eq. 73).221 In the same way, isopropenylcyclopropane gives an 80% yield of deuterated isopropylcyclopropane after 30 minutes at −10◦ (Eq. 74).221 Et3SiD TFA, 50° Et3SiD TFA, –10°
(90%)
(Eq. 73)
(80%)
(Eq. 74)
D D
38
ORGANIC REACTIONS
Preferential protonation of oxygen in comparison to carbon prevents 4-methylenetetrahydropyran from undergoing reduction to 4-methyltetrahydropyran even when held at 70◦ for 10 hours in the presence of triethylsilane and a 20-fold excess of trifluoroacetic acid.146 However, when the reaction conditions are changed so that a dichloromethane solution of the same substrate is treated with a mixture of four equivalents of triethylsilane and three equivalents of aluminum chloride in the presence of excess hydrogen chloride, a 40% yield of 4-methyltetrahydropyran product is obtained at room temperature after one hour (Eq. 75).136
Et3SiH O
(40%)
HCl, AlCl3
(Eq. 75)
O
The cis-to-trans ratios of the isomeric 4-tert-butyl-1-methylcyclohexanes derived from treatment of 4-tert-butyl-1-methylenecyclohexane with trifluoroacetic acid vary with the steric features of the organosilicon hydrides that are used (Eq. 76).204 The ratio is 0.04 with n-butylsilane, 0.09 with diethylsilane, 0.11 with triethylsilane, 0.10 with triisopentylsilane, and 0.19 with either tri-sec-butylsilane or di-tert-butylsilane. R3SiH
(—) cis:trans = 0.04-0.19
TFA, rt
(Eq. 76)
Trisubstituted Alkenes. With very few exceptions, trisubstituted alkenes that are exposed to Brønsted acids and organosilicon hydrides rapidly undergo ionic hydrogenations to give reduced products in high yields. This is best illustrated by the broad variety of reaction conditions under which the benchmark compound 1methylcyclohexene is reduced to methylcyclohexane.134,146,192,202,203,207 – 210,214,234 When 1-methylcyclohexene is reduced with one equivalent of deuterated triethylsilane and two equivalents of trifluoroacetic acid at 50◦ , methylcyclohexane1-d1 is obtained in 80% yield after 24 hours (Eq. 77).221 Under similar conditions, 2-methyl-2-butene gives 2-methylbutane-2-d1 (90%) and 1-methylcyclopentene gives methylcyclopentane-1-d1 (60%).221 D Et3SiD
(80%)
(Eq. 77)
TFA, 50°
Surprisingly, α-cyanoacrylic acid is reported to react spontaneously with triethylsilane in the absence of any additional acid to give a quantitative yield of the triethylsilyl ester of α-cyanopropionic acid.236 Ethyl α-cyanoacrylate requires the presence of trifluoroacetic acid to undergo reduction to ethyl 2-cyanopropionate.236 Many of these reductions are highly stereoselective. For example, treatment of
ORGANOSILICON HYDRIDE REDUCTIONS
39
2-phenylnorbornene with a solution of trifluoroacetic acid and triethylsilane in dichloromethane is reported to yield only endo-2-phenylnorbornane (Eq. 78).164 Et3SiH Ph
(Eq. 78)
(100%)
TFA, CH2Cl2
Ph
A mixture of Et3 SiH/TFA in dichloromethane reduces 3-methyl-5-α-cholest2-ene to give the pure equatorial methyl isomeric product, 3β-methyl-5αcholestane, in 66% yield (Eq. 79).126 On the other hand, attempts to reduce cholest-5-ene using the same technique yield neither 5α-cholestane nor 5βcholestane, but instead an isomeric mixture of rearranged olefins. This result is presumably because of the inability of hydride attack to compete with carbocation skeletal isomerization and elimination.126
Et3SiH
(Eq. 79)
TFA, CH2Cl2 (66%)
Treatment with trifluoroacetic acid and triethylsilane causes octahydro-6,7,8, 12,13,14,16,17-15H -cyclopenta[a]phenanthrene to form decahydro-6,7,8,9,11,12, 13,14,16,17-15H -cyclopenta[a]phenanthrene by reduction of the conjugated double bond.237 Similar treatment of the 3-methyl ether of 9(11)-dehydro-D-homoestrol gives the 3-methyl ether of estradiol in better than 50% yield.226 A similar transformation occurs as a critical step in the total synthesis of (+)estrone by a Diels-Alder cycloaddition-cycloreversion pathway (Eq. 80).227 It is worth noting that in this reaction the conjugated double bond is stereoselectively reduced while both an isolated double bond and a ketone carbonyl are preserved. O
O H
H Et3SiH
H
H
TFA, CH2Cl2
H H MeO
H
(Eq. 80) H H
MeO (87%)
Treatment of progesterone with trifluoroacetic acid and triethylsilane in dichloromethane followed by saponification of the mixture of the trifluoroacetate ester intermediates of 5-β-pregnane-3α,20β-diol and 5-β-pregnane-3α,20α-diol and Jones oxidation yields 5-β-pregnanedione in 65% yield (Eq. 81).238 O
H O
O
1. TFA, Et3SiH, CH2Cl2 2. H2O, OH–
(Eq. 81)
3. CrO3, Me2CO
H O
(65%)
40
ORGANIC REACTIONS
Hydrogenation of the carbon-carbon double bond occurs without alteration of the ester function when citronellyl acetate is treated with 2.5 equivalents of trifluoroacetic acid and two equivalents of triethylsilane in 2-nitropropane.205 The reduced product is obtained in 90% yield after 22 hours at room temperature in the presence of one equivalent of added lithium perchlorate (Eq. 82). The yields are lower in the absence of this added salt. Similar reduction of an unsaturated phenolic chroman derivative occurs to give an 85% yield of product with only the carbon-carbon double bond reduced (Eq. 83).205 TFA, Et3SiH, LiClO4 OAc
OAc
(CH3)2CHNO2
(Eq. 82)
(90%) HO
TFA, Et3SiH, LiClO4
HO
(Eq. 83)
(CH3)2CHNO2
O
O (85%)
A dichloromethane solution of 4-methyl-5,6-dihydro-2H -pyran gives 4-methyltetrahydropyran in 35% yield when treated with a mixture of five equivalents of triethylsilane and 2.5 equivalents of aluminum chloride in the presence of excess hydrogen chloride at room temperature for one hour (Eq. 84).136 This behavior is essentially the same as that exhibited by the disubstituted 4methylenetetrahydropyran isomer under similar conditions.136 Et3SiH TFA
O
(35%)
(Eq. 84)
O
Exceptions to the generally facile ionic hydrogenation of trisubstituted alkenes include the resistance of both 2-methyl-1-nitropropene (R = NO2 ) and 3,3-dimethylacrylic acid (R = CO2 H) to the action of a mixture of triethylsilane and excess trifluoroacetic acid at 50◦ (Eq. 85).234 The failure to undergo reduction is clearly related to the unfavorable effects caused by the electron-withdrawing substituents on the energies of the required carbocation intermediates. R
Et3SiH TFA
No Reaction
(Eq. 85)
R = NO2, CO2H
Tetrasubstituted Alkenes. Tetrasubstituted alkenes lacking electron-withdrawing substituents undergo facile ionic hydrogenation to alkanes in very good yields. Simple examples include 2,3-dimethyl-2-butene,208,214 1,2-dimethylcyclopentene, 1,2-dimethylcyclohexene,229 and 9(10) -octalin.126,204,212 Interesting variations are observed in the stereoselectivities of these ionic hydrogenations. Reduction of 1,2-dimethylcyclopentene with Et3 SiH/TFA near
ORGANOSILICON HYDRIDE REDUCTIONS
41
room temperature gives 1,2-dimethylcyclopentane with a cis to trans ratio of 0.083, compared to a ratio of 0.63 for 1,2-dimethylcyclohexene.229 The reduction of 9(10) -octalin to cis- and trans-decalins occurs with cis to trans stereoselectivities that vary with the nature of the organosilicon hydride employed. The ratios are 0.28–0.59 with n-butylsilane, 0.67 with diethylsilane,204 0.34212 or 0.72204 with triethylsilane, 0.67 with diphenylsilane, 0.77 with diphenylmethylsilane,212 1.38204 –1.80127,212 with triphenylsilane, 0.54 with triisopentylsilane, 1.17 with tricyclopentylsilane, 2.57 with tri-sec-butylsilane, 3.35 with di-tert-butylsilane, 4.88 with di-tert-butylmethylsilane, and 13.3 with tri-tertbutylsilane.204 Opinions differ about the mechanistic significance of these changes in isomer ratios.204,212 Treatment of 8(9) -dehydroestradiol with trifluoroacetic acid and triethylsilane gives estradiol in 96% yield (Eq. 86).239 The 3-methyl ether is similarly reduced to the 3-methyl ether of estradiol in >50% yield.239 The structurally related 18-ethyl and 18-propyl 17-keto compounds experience reduction of the 8(9) function in excess of 70% yield without concomitant reduction of the 17-keto group.239 OH
OH Et3SiH
H
H
TFA
HO
H
(Eq. 86)
(96%) H
HO
Treatment of 8(9) -dehydro-D-homoestradiol (39, R = H) (or its 3-methyl ether, R = Me) with Et3 SiH/TFA followed by saponification of the trifluoroacetate ester intermediate leads to D-homoestradiol (40) (or its 3-methyl ether) containing 2–15% D-homoequilenol (41) (or its 3-methyl ether).240 By contrast, reduction and saponification of 3,17-diacetyl- 8(9) -dehydro-D-homoestradiol (39, R = AcO) gives a 60% yield of D-homoestradiol without the presence of any D-homoequilenol (Eq. 87).240 OR
OH 1. TFA, Et3SiH
H RO
H
2. NaBH4
H
H
HO 39
40 R = Ac (60%)
OH
(Eq. 87)
+ H HO 41 R = Ac (0%)
Polyenes. The behavior of substrates with multiple carbon-carbon double bonds toward the conditions employed for ionic hydrogenations with organosilicon hydrides depends heavily on the number and kinds of substituents and
42
ORGANIC REACTIONS
whether or not the multiple double bonds are conjugated. In the absence of conjugation, the individual double bonds react independently. The full reduction of 1,3-dienes with Et3 SiH/TFA occurs in certain systems although the yields are only modest.231 For example, 1,3-cyclohexadiene gives a 65% yield of cyclohexyl trifluoroacetate, presumably by way of cyclohexene (Eq. 88).211 On the contrary, 1,4-cyclohexadiene fails to undergo reaction with 10 equivalents of triethylsilane and 20 equivalents of trifluoroacetic acid even after 24 hours at room temperature (Eq. 89). O2CCF3
Et3SiH
TFA
(65%)
TFA Et3SiH
(Eq. 89)
No Reaction
TFA
(Eq. 88)
Additional evidence of this pattern of behavior is shown upon treatment of the conjugated diene 1-propenylcyclohexene with two equivalents of triethylsilane and three equivalents of trifluoroacetic acid at 50◦ . This diene gives a 70% yield of completely reduced propylcyclohexane after 10 hours (Eq. 90).231 No partially reduced intermediates are found. Et3SiH
(70%)
TFA
(Eq. 90)
Similar treatment of the isomeric, nonconjugated 1-(3-propenyl)cyclohexene gives a mixture of products containing 55% of the partially reduced 3-propenylcyclohexane and 15% of the completely reduced propylcyclohexane (Eq. 91).231 The yield of the latter product increases to 25% when the amounts of Et3 SiH/TFA used are raised to 6.5 and 12.1 equivalents, respectively, and the reaction time is increased to 24 hours.230 The nonconjugated 1-(3-butenyl)cyclohexene gives a 65% yield of partially hydrogenated 3-butenylcyclohexane under identical conditions.231 Et3SiH
+
(Eq. 91)
TFA (55%)
(15%)
Reduction of dienes incorporated into steroid structures may lead to different configurations in the products. For example, treatment of 8(9),14(15)bisdehydroestrone 42 (R = H) for four hours at room temperature with twenty equivalents of trifluoroacetic acid and two equivalents of triethylsilane leads to an ionic hydrogenation product mixture containing the natural 8β,9α,14α-estrone 43 as a minor component (11%) and the 8α,9β,14β-isomer 44 as the major component (83%) (Eq. 92).241 The related methyl ether (42, R = Me) behaves in a similar fashion.241 The yield of natural isomer 46 formed from the methyl ether of 8(9),14(15) -bisdehydroestradiol analog 45 increases from 22 to 34%, and that of
ORGANOSILICON HYDRIDE REDUCTIONS
43
isomer 47 decreases from 78 to 66%, when the solvent is changed from benzene to dichloromethane (Eq. 93).242 O
O Et3SiH
H
TFA RO
+ H
H RO
42
O
43 R = H (11%) R = Me (27%)
(Eq. 92)
H H
H
RO 44 R = H (83%) R = Me (66%) OH
OH Et3SiH
H
TFA MeO
H
H MeO
OH
46 (22-34%)
45
(Eq. 93)
H
+ H
H
MeO 47 (78-66%)
Treatment of linalyl p-tolyl sulfone (R = SO2 C6 H4 Me-p) with 2.5 equivalents of trifluoroacetic acid and two equivalents of triethylsilane in 2-nitropropane containing one equivalent of lithium perchlorate gives, after 20 hours at room temperature, an 87% yield of the product in which only the double bond distal to the sulfone function is reduced (Eq. 94).205 TFA, Et3SiH, LiClO4 (CH3)2CHNO2
R
(Eq. 94)
R R = Ts (87%)
Surprisingly, linalyl acetate (R = OAc) fails to undergo reduction under these conditions; instead, it rapidly decomposes through cyclization and polymerization pathways.205 The same reaction conditions transform geranyl p-tolyl sulfone (R = SO2 C6 H4 Me-p) into a mixture of 7% reduced and 93% cyclized products within 20 hours, whereas geranyl acetate (R = OAc) gives only a 20% yield of cyclized and no reduced product (Eq. 95).205 TFA, Et3SiH, LiClO4 R
R
(CH3)2CHNO2 R = Ts (7%) R = OAc (0%)
R
+ (93%) (20%)
(Eq. 95)
44
ORGANIC REACTIONS
Homoconjugation results in enhanced reactivity of substrates toward ionic hydrogenation. Bicyclo[2.2.1]hepta-2,5-diene forms a mixture of the trifluoroacetate esters of bicyclo[2.2.1]hepten-2-ol, tricyclo[2.2.1.02,6 ]heptan-3-ol, and bicyclo[2.2.1]heptan-2-ol in a 62 : 20 : 17 ratio on treatment with 10 equivalents of triethylsilane and 20 equivalents of trifluoroacetic acid for 24 hours at room temperature (Eq. 96).230 Et3SiH O2CCF3 +
TFA
O2CCF3 +
O2CCF3
(Eq. 96)
(—) 62:20:17
Treatment of 5-methylenebicyclo[2.2.1]hept-2-ene with 10 equivalents of triethylsilane and 20 equivalents of trifluoroacetic acid either for 24 hours at room temperature or 3 hours at 50◦ gives an 85% yield of completely hydrogenated endo-2-methylbicyclo[2.2.1]heptane (Eq. 97). The combination of Et3 SiH/TFA/ BF3 •OEt2 gives this product in 80% yield.230 The reaction presumably proceeds by way of 2-methyltricyclo[2.2.1.02,6 ]heptane as a reaction intermediate, since this compound is expected to rapidly give the same final product when it is subjected to these reaction conditions.230 The analogous stereospecific behavior is exhibited by 5-ethylidenebicyclo[2.2.1]hept-2-ene.230 Et3SiH
Et3SiH
TFA
TFA
(85%)
(Eq. 97)
Transannular interactions lead to ring closures and reductions to adamantane compounds when dienes of the bicyclo[3.3.1]nonane family are treated with Brønsted acids and triethylsilane. Compounds 48–51 form reaction mixtures containing various amounts of products 52–54 (R = OH, O2 CCF3 , Cl) under such conditions.243 The best yields of hydrocarbon 52 occur when the dienes are treated with a 25% excess of sulfuric acid and a 50% excess of triethylsilane in dichloromethane at 20◦ .243 The stereospecific nature of these transannular reductions is demonstrated by the observation that the enantiomeric purity of the chiral diene 55 is retained in the chiral hydrocarbon product 56 (Eq. 98).243 Dienes of
48
49
50
51
R 52
53 R = OH, OTFA, Cl
54
ORGANOSILICON HYDRIDE REDUCTIONS
45
the type shown can be reduced to the chlorides (Eq. 99).243 When HCl is replaced with TFA, methyladamantane and methyladamantanol are formed (Eq. 100). Ph
Et3SiH, CH2Cl2
Ph
(73%)
H2SO4 55
(Eq. 98)
56 Et3SiH, HCl
(Eq. 99)
(96%)
CH2Cl2, rt, 6 h
Cl
Et3SiH, TFA
+
CH2Cl2, rt, 6 h
(Eq. 100)
OH (29%)
(45%)
Alkynes to Alkanes. In contrast to the facile ionic hydrogenations that many alkenes undergo, alkynes as a group are very resistant to reduction with the organosilicon hydride/acid combinations. Only those alkynes having an electronrich aryl group in conjugation with the carbon-carbon triple bond give even modest amounts of reduced products as seen in the example of p-tolylacetylene (Eq. 101).244 Alkenes are not observed as products.244 Et3SiH, TFA rt, 120 h
(Eq. 101)
(21%)
The use of stronger acid conditions provides somewhat better synthetic yields of alkanes from alkynes. A useful method consists of treatment of the substrate with a combination of triethylsilane, aluminum chloride, and excess hydrogen chloride in dichloromethane.146 Thus, treatment of phenylacetylene with 5 equivalents of triethylsilane and 0.2 equivalents of aluminum chloride in this way at room temperature yields 50% of ethylbenzene after 1.5 hours. Diphenylacetylene gives a 50% yield of bibenzyl when treated with 97 equivalents of triethylsilane and 2.7 equivalents of aluminum chloride after 2.8 hours. Even 1-hexyne gives a mixture of 44% n-hexane and 7% methylpentane of undisclosed structure when treated with 10 equivalents of triethylsilane and 0.5 equivalent of aluminum chloride for 0.5 hour.146 The reductive cyclization of enynes has been used to prepare exo-methylenecycloalkanes. Two systems have proven successful in this transformation, namely PMHS/Pd2 (dba)3 •CHCl3 245 (Eq. 102) and Et3 SiH/Pd(dppe)Cl2 /HCO2 H (Eq. 103).246 PMHS, Pd2(bpa)3•CHCl3, (o-Tol)3P TBSO
OTMS
HOAc, ClCH2CH2Cl, rt
TBSO
(90%) OTMS
(Eq. 102)
46
ORGANIC REACTIONS
O
Et3SiH, Pd(dppe)Cl2, HCO2H
Ph
1,4-dioxane, 70°, 10 h
O
+
Ph
O
(Eq. 103)
Ph (73%)
(8%)
The triethylsilane/Pd2 (dba)3 combination is also used for these reductive cyclizations, although lower yields are reported.247 1,6-Diynes are reductively cyclized to 1,2-dialkylidenecyclopentanes in good yields with Et3 SiH/Pd2 (dba)3 •CHCl3 (Eq. 104).248 OMe
OMe Et3SiH, Pd2(dba)3•CHCl3
TBSO
TBSO
(o-Tol)3P, HOAc, rt, 15 min
H
(86%)
(Eq. 104)
o-Bromobenzyl alkynylalkyl ethers can be reductively cyclized in modest yields with Et3 SiH/Pd(PPh3 )4 /Cs2 CO3 as shown in Eq. 105.249 In a like manner, enynes with a vinyl bromide as the olefin function undergo reductive cyclization (Eq. 106).249 O
Cs2CO3, DMF, 80°, 3 h
Br EtO2C EtO2C
O
Et3SiH, Pd(PPh3)4
Br
Et3SiH, Pd(PPh3)4
EtO2C
Cs2CO3, DMF, 80°, 4 h
EtO2C
(48%)
(Eq. 105)
(72%)
(Eq. 106)
Cyclopropanes to Alkanes. Cyclopropanes that can form ring-opened tertiary aliphatic or benzylic carbenium ion intermediates undergo ionic hydrogenation with reasonable ease when treated with Brønsted acids and organosilicon hydrides. Ring opening occurs preferentially between the most and least highly substituted ring carbons. For example, treatment of 1,1,2trimethylcyclopropane with one equivalent of triethylsilane and two equivalents of trifluoroacetic acid gives a mixture of 2,3-dimethylbutane (75%) and 2methylpentane (25%) (Eq. 107).233 The conversion into the hydrocarbon mixture is 15% after 15 minutes, 65% after 12 hours, and complete after 16 hours at room temperature.222,232 Essentially the same results are obtained when 2,3dimethyl-2-butene is used as the substrate.222 The disubstituted isomer 1-methyl2-ethylcyclopropane gives an alkane reaction mixture consisting primarily of 3-methylpentane along with 2-methylpentane (Eq. 108).222 Et3SiH
+
(Eq. 107)
TFA (75%)
(25%)
ORGANOSILICON HYDRIDE REDUCTIONS Et3SiH
+
TFA
47
(Eq. 108)
(major)
(minor)
Unlike its disubstituted isomer, the monosubstituted isopropylcyclopropane undergoes reduction to 2-methylpentane to the extent of only 50% after 24 hours (Eq. 109),232 a result similar to that observed when 2-methyl-1-pentene is the substrate.222 It is interesting that deuterated triethylsilane produces 2-methylpentane that contains the deuterium label only at the C2 position.250 This label position suggests that in this reaction ring protonation and opening are followed by a 1,2-hydride shift that precedes capture by the silyl hydride of any initially formed carbocation intermediates.250 Ethylcyclopropane, with an unbranched side chain, shows no sign of reduction under these conditions even after 200 hours.232 Phenylcyclopropane is reduced to 1-phenylpropane.222 Et3SiD
(Eq. 109)
(50%)
TFA, rt
D
Bicyclic hydrocarbons that contain a three-membered ring slowly undergo ionic hydrogenation when treated with at least one equivalent of triethylsilane and an excess of trifluoroacetic acid at room temperature.229 Thus, bicyclo[3.1.0]hexane gives a product mixture containing methylcyclopentane (28%) and cyclohexane (3%) when reacted with one equivalent of triethylsilane and four equivalents of trifluoroacetic acid for 140 hours (Eq. 110). The main products are the trifluoroacetates of cyclohexanol and cis-and trans-2-methylcyclopentanol in a ratio of 10 : 35.229 Under the same conditions, bicyclo[4.1.0]heptane yields a mixture containing mainly methylcyclohexane (79%) with some cycloheptane (5%) and the corresponding trifluoroacetates (16%) (Eq. 111).229 Et3SiH TFA Et3SiH TFA
(28%)
(79%)
+
+
(3%)
(Eq. 110)
(15%)
(Eq. 111)
After ten days at room temperature in the presence of one equivalent of triethylsilane and two equivalents of trifluoroacetic acid, both 1-methylbicyclo[3.1.0]hexane and 1-methylbicyclo[4.1.0]heptane form mixtures of the two isomers of their respective 1,2-dimethylcycloalkanes (Eqs. 112 and 113).229 Et3SiH TFA Et3SiH TFA
(89%) trans:cis = 10.0
(Eq. 112)
(74%) trans:cis = 1.5
(Eq. 113)
48
ORGANIC REACTIONS
Based on the few reported examples, the pattern of ring cleavage that accompanies the ionic hydrogenation of alkylidenencyclopropanes seems to be related to the pattern and degree of substitution on both the ring and the double bond.233 Thus, treatment of 1,1-dimethyl-2-methylenecyclopropane with two equivalents of triethylsilane and four equivalents of trifluoroacetic acid for 90 hours at room temperature yields 65% of 2,3-dimethylbutane (Eq. 114).229 Exposure of 1,1dimethyl-2-isopropylidenecyclopropane to the same ratio of reactants at 50◦ for 16 hours produces a complex mixture containing 63% of 2,5-dimethylhexane, 18.5% of 2,5-dimethyl-3-hexene, 1.6% of 2,5-dimethyl-2-hexene, and 7% of 2,5-dimethyl-2-hexyl trifluoroacetate (Eq. 115).229 Et3SiH
Et3SiH
(63%)
TFA
(Eq. 114)
(65%)
TFA
+
+
(1.6%)
(18.5%)
+
O2CCF3 (7%)
(Eq. 115) Aromatic Substrates. Aromatic hydrocarbons can be reduced with organosilanes to dienes, alkenes, or alkanes. The combination of Et3 SiH/TFA/BF3 •OEt2 reduces furans to tetrahydrofurans in good yields (Eq. 116).211 In general, poor yields are obtained with the Et3 SiH/TFA reduction of benzofurans,251 but the C3substituted benzofuran shown undergoes reduction of the furan ring in excellent yield with this reagent (Eq. 117).252 Similarly, benzothiophenes are reduced in 60 to 90% yields under the same conditions.253 The Et3 SiH/TFA system reduces thiophenes to tetrahydrothiophenes in good yields.254 – 257 In α-hydroxy thiophenes, both double bonds of the thiophene unit and the hydroxy group are reduced (Eq. 118).258 Et3SiH, TFA, BF3•OEt2 O
20°, 4 min Et3SiH, TFA, 20°, 1.5 h
(95%)
O
S
C15H31-n OH
(Eq. 116)
(70%)
O
(Eq. 117)
O Et3SiH, TFA, 50°, 48 h S
C16H33-n
(—)
(Eq. 118)
Similar reactivity is realized with 2-acetylthiophene using triethylsilane with aluminum chloride.259 Treatment of the ethylene glycol acetal of 2-thiophenecarbaldehyde with Et3 SiH/TFA results in reduction of the ring and oxidation of
ORGANOSILICON HYDRIDE REDUCTIONS
49
the side chain to the silylated carboxylic acid (Eq. 119),260 whereas similar treatment of 2-thiophenecarbaldehyde gives 2-methyltetrahydrothiophene and 2acetylthiophene gives 2-ethylthiophene.257 Some thiophenes are reduced to a mixture of tetrahydrothiophenes and 2,5-dihydrothiophenes.210,259,261 Et3SiH, TFA, 55°, 15 h
O S
O S
O
(45%)
(Eq. 119)
OSiEt3
Partial reduction of polyarenes has been reported. Use of boron trifluoride hydrate (BF3 •OH2 ) as the acid in conjunction with triethylsilane causes the reduction of certain activated aromatic systems.217,262 Thus, treatment of anthracene with a 4–6 molar excess of BF3 •OH2 and a 30% molar excess of triethylsilane gives 9,10-dihydroanthracene in 89% yield after 1 hour at room temperature (Eq. 120). Naphthacene gives the analogously reduced product in 88% yield under the same conditions. These conditions also result in the formation of tetralin from 1-hydroxynaphthalene (52%, 4 hours), 2-hydroxynaphthalene (37%, 7 hours), 1-methoxynaphthalene (37%, 10 hours), 2-methoxynaphthalene (26%, 10 hours), and 1-naphthalenethiol (13%, 6 hours). Naphthalene, phenanthrene, 1-methylnaphthalene, 2-naphthalenethiol, phenol, anisole, toluene, and benzene all resist reduction under these conditions.217 Use of deuterated triethylsilane to reduce 1-methoxynaphthalene gives tetralin-1,1,3-d3 as product, thus yielding information on the mechanism of these reductions.262 2-Mercaptonaphthalenes are reduced to 2,3,4,5-tetrahydronaphthalenes in poor to modest yields.217,263 Et3SiH, BF3•OH2
(89%)
CH2Cl2, rt, 1 h
(Eq. 120)
The combination of PhMeSiH2 (or Ph2 SiH2 ) and Cp2 TiMe2 (10 mol%) reduces pyridines to N-silylated-di- or tetrahydropyridines or the N-silylated piperidines.264,265 With quinoline, only the pyridine ring is reduced preferentially to the benzene ring (Eq. 121). PhMeSiH2, Cp2TiMe2
+ N SiPhMeH (56%)
80°, 8 h
N
N SiPhMeH (18%)
(Eq. 121)
Miscellaneous Unsaturated Substrates. Exposure of 1,1 -bis(trans-2cyanovinyl)ferrocene to a mixture of two equivalents of triethylsilane and 320 equivalents of trifluoroacetic acid at 50◦ for three hours gives a product with the carbon-carbon double bonds reduced in 83% yield, but leaving the nitrile groups intact (Eq. 122).179 CN Fe
CN
CN
Et3SiH TFA
Fe
(Eq. 122) CN
50
ORGANIC REACTIONS
Treatment of a chloroform or dichloromethane solution of 1-bromo-2,2-diphenylethene or 1-bromo-2,2-bis(4 -methoxyphenyl)ethene with a slight excess of triethylsilane and a 9- to 10-fold excess of TFA gives the corresponding ethanes in 62% and 88% yields, respectively, after one hour at 0◦ (Eq. 123).184 Ar Ar
Ar
Et3SiH Br
TFA Ar Ph 4-MeOC6H4
Br Ar
(Eq. 123) (62%) (88%)
The carbonyl groups of 1,3-indanediones are generally resistant to the action of combinations of acid and silanes at room temperature.266 Accordingly, treatment of a variety of 2-benzylidene-1,3-indanediones with Et3 SiH/TFA (ratio of 1 : 5 : 10) in CCl4 at 55◦ for 7–20 hours gives the corresponding substituted 2benzyl-1,3-indanediones in 54-78% yields (Eq. 124).266 Use of a 27-fold excess of trifluoroacetic acid in the absence of a cosolvent reportedly leads to reduction of the carbonyl groups to give a mixture of products.267 O
O Et3SiH
CHAr O
(Eq. 124)
CH2Ar
TFA O
An interesting hydroiodination reaction occurs when a mixture of cyclohexene and triethylsilane in dichloromethane is treated with a mixture of bis(pyridine) iodonium tetrafluoroborate and tetrafluoroboric acid in diethyl ether (Eq. 125). A 50% yield of iodocyclohexane is produced after one hour at 20◦ .268 I
Et3SiH
(Eq. 125)
I(py)2BF4, HBF4
Reduction of Ethers Because of the high stability of the triphenylmethyl carbocation, the reductive ether cleavage of trityl ethers with Et3 SiH/trimethylsilyl triflate (TMSOTf) is highly successful. This reaction even occurs in the presence of highly reactive sugar ketals, leaving the ketals intact (Eq. 126).269 OTr BzO BzO
OH O
BzO O
OTr O OH
Et3SiH, Et3SiOTf CH2Cl2, rt, 5 min OTr
OH
BzO BzO
O BzO O
OH O OH
+ Ph3CH OH
OH (87%)
(Eq. 126) The combination of PMHS and Pd(PPh3 )4 reduces allyl ethers to propene and alcohols.270 The best combination for the reductive cleavage of ethers appears
ORGANOSILICON HYDRIDE REDUCTIONS
51
to be Et3 SiH/(C6 F5 )3 B, which gives excellent yields of the alcohol (via the silyl ether) and alkane (Eq. 127).145 n-C16H33
O
Et3SiH, (C6F5)3B C16H33-n
n-C16H34 (98%) + n-C16H33OSiEt3 (98%)
CH2Cl2, rt, 20 h
(Eq. 127) Dialkyl ethers are reduced with the combination of Et3 SiH/TFA, although the yields vary.144,271 tert-Butyl triphenylcyclopropenyl ether is reduced to the corresponding cyclopropene (Eq. 128),272 and a dibenzyl-like ferrocene-derived ether is reduced to the corresponding alkane (Eq. 129).179 Ph
Ph
Et3SiH, TFA
Ph
Fe
OBu-t
Ph
Et3SiH, TFA, rt, 3 h O
(Eq. 128)
(45%)
Ph Ph
Fe
Ph
Ph
(80%)
(Eq. 129)
Reduction of Allyl Acetates Allyl acetates are reduced to the corresponding olefins with PMHS/Pd(PPh3 )4 or Ph2 SiH2 /Pd(PPh3 )4 .196,273 Unfortunately, double bond migration occurs in many of these reactions (Eqs. 130 and 131).196,273 The combinations of Ph2 SiH2 / Pd(P(Tol-p)3 )4 /ZnCl2 274 and Et3 SiH/TFA275 are also employed in this transformation. PMHS, Pd(PPh3)4 +
PPh3, THF, 5 d
OAc
(48%)
(52%)
(Eq. 130) OAc
Ph2SiH2, Pd(PPh3)4
CN
THF, rt, 30 h
CN
(Eq. 131)
(100%)
The Et3 SiH/TFA reduction of a 3-acetoxy enol ether is reported. The diastereoselectivity is high for the Z isomer, but much lower for the E isomer (Eq. 132).276 BnO Ph
PhMe2SiH, TFA OAc
rt, 16 h
BnO Ph
BnO OAc
+ Ph
OAc
(Eq. 132)
(73%) syn:anti = 99:1
Reduction of Carboxylic Acids Aromatic and aliphatic carboxylic acids are reduced to the trifluoroacetates of the alcohol with Et3 SiH/TFA.277 Use of an excess of the triethylsilane can give
52
ORGANIC REACTIONS
further reduction to the methyl group. The combination of PMHS/TBAF (tetran-butylammonium fluoride) reduces benzoic acids to the benzyl alcohols in good yields.278 Comparable yields of this useful transformation can be realized through the use of PMHS/Ti(OPr-i)4 (or PMHS/Ti(OEt)4 ).279 Both aromatic and aliphatic carboxylic acids can be reduced with EtMe2 SiH and the ruthenium-based catalyst 57 (Eq. 133).280 The latter reagent/catalyst combination also reduces esters to alcohols in high yield. O OH
EtMe2SiH, 57
OH
1,4-dioxane, 20°, 0.5 h
(72%)
(Eq. 133) (CO)2Ru
Ru(CO)2 Ru (CO)2 O 57
The highly reactive reagent combination of Et3 SiH/(C6 F5 )3 B reduces carboxylic acids to methyl groups (Eq. 134).281,282 Isolation of the intermediate silyl ether is also possible.282 CO2H
Et3SiH, (C6F5)3B
(94%)
CH2Cl2, rt, 20 h
(Eq. 134)
Benzoic acids with electron-donating groups on the ring are reduced to toluene derivatives with the reagent combination Et3 SiH/TFA/TFAA.283 p-Anisic acid gives 4-methylanisole in 97% yield under these conditions (Eq. 135). Formation of the corresponding benzyl trifluoroacetates occurs for substrates without activating groups. p-Nitrobenzoic acid is unreactive under these conditions, as are dibasic acids such as phthalic or succinic acid.283 The same conditions reduce alkyl carboxylic acids to trifluoroacetates.277 Use of the silane 58 or 59 provides cinnamaldehyde in fair yield from cinnamic acid (Eq. 136).284 CO2H
Et3SiH, TFA, (CF3CO2)2O 60°, 5 h
MeO O Ph
Ph Ph SiH2
Ph Si H H
NMe2 58
(Eq. 135)
O
58 or 59, >180° OH
(97%) MeO
NMe2 59
H
58 (65%) 59 (50%)
(Eq. 136)
ORGANOSILICON HYDRIDE REDUCTIONS
53
Reduction of Acid Halides and Acid Anhydrides The organosilane reduction of acid chlorides to aldehydes has been accomplished in high yields with the use of the pentacoordinated organosilane 60 (Eq. 137).107 This transformation has been reported to occur with tribenzylsilane and triethylsilane, but yields were not reported.285,286 O Cl
O
60, rt
Cl
H
H
O
(85%)
O Ph SiHMe NMe2
(Eq. 137)
60
The combination Et3 SiH/(C6 F5 )3 B reduces acid chlorides to methyl groups (Eq. 138).281,282 If a smaller amount of triethylsilane is used, the same combination reduces aryl acid chlorides to the trimethylsilyl ethers of the benzyl alcohols.281,282 O n-C13H27
Et3SiH, (C6F5)3B CH2Cl2, rt, 20 h
Cl
n-C14H30
(Eq. 138)
(97%)
One study of the Et3 SiH/TFA reduction of acid anhydrides reports the formation of one equivalent each of the alcohol and the trifluoroacetate ester of the acid (Eq. 139).287 O n-C3F7
O O
Et3SiH, TFA 50°, 3 h
C3F7-n
n-C3F7CH2OH +
n-C3F7CH2O2CCF3
(Eq. 139)
(60%)
Reduction of Esters and Lactones The combination of (EtO)3 SiH/CsF (or KF) provides a convenient reagent for the reduction of esters to alcohols.76,80,83 The yields are in the 70% range. Potassium tetraethoxyhydridosilicate also reduces esters in moderate yields.288 The combination of PMHS/Cp2 TiCl2 /n-BuLi reduces esters in high yields even in the presence of an epoxide and a trisubstituted olefin (Eq. 140).289 The reagent combination can reduce a methyl ester in the presence of a tert-butyl ester (Eq. 141).290 PMHS, Cp2TiCl2, n-BuLi
H O
O MeO
OEt
H
THF, rt, 1 h O
O
O
THF, –78°, 1 h
(Eq. 140)
O
PMHS, Cp2TiCl2, n-BuLi OBu-t
(91%) OH
(87%) HO
OBu-t
(Eq. 141)
54
ORGANIC REACTIONS
Ester reductions with (EtO)3 SiH/(EBTHI)TiCl2 /n-BuLi (EBTHI = ethylenebis(η5 -tetrahydroindenyl)titanium) result in good yields of the corresponding alcohols.290 Excellent yields of alcohols result from the reduction of esters with the PMHS/Ti(OPr-i)4 system.279,291,292 The reaction catalyzed by (EBTHI)TiCl2 / n-BuLi occurs in lower yields.289 Methyl cinnamate is reduced with PMHS/TBAF in good yield.278 The ruthenium complex 57 (Eq. 135) catalyzes the EtMe2 SiH reduction of esters to alcohols, although a mixture of the alcohol and the ether are often obtained (Eq. 142).280 O
EtMe2SiH, 57 OEt
OH
1,4-dioxane, 20°, 0.5 h
OEt
+
(55%)
(11%)
(Eq. 142) High yields in the reduction of esters with Ph2 SiH2 /[RhCl(cod)]2 are reported.293 The combination of (MeO)3 SiH/LiOMe is reported to reduce esters to the alcohols, although the advantages of this system over others does not seem to warrant working with the highly hazardous trimethoxysilane.294 The reduction of the carbonyl group of an ester or lactone is possible. This results in the formation of the corresponding ether. This reaction can be carried out employing PhSiH3 /(PPh3 )(CO)4 MnC(O)Me,295 PhSiH3 /Mn(CO)5 Br,295 Cl3 SiH/γ -irradiation,296 or Et3 SiH/TiCl4 /TMSOTf.297 The reduction of lactones to cyclic ethers is nicely accomplished with the EtMe2 SiH/ruthenium catalyst system 57 (Eq. 143).280 The same transformation can be carried out with Et3 SiH/TiCl4 297 or PhSiH3 /Mn(CO)5 Br.295 The reductive etherification of esters occurs by treating an ester with Et3 SiH/ZnCl2 (Eq. 144).298 EtMe2SiH, 57 n-C7H15
O
O
1,4-dioxane, 20°, 0.5 h Et3SiH, ZnCl2
O OEt
heat, 3-4 h
n-C7H15
(79%)
O
O
(76%)
(Eq. 143) (Eq. 144)
The reduction of esters to aldehydes is a useful transformation and can be accomplished in good yields with Et3 SiH/[RuCl2 (CO)3 ]2 299 or with Ph3 SiH/ (C6 F5 )3 B.116 Thio esters are reduced to aldehydes in good yields with Et3 SiH/Pd/C.300 Lactones can be reduced to hemiacetals with PMHS/Cp2 TiF2 or PMHS/Cp2 Ti(OC6 H4 Cl-4)2 (Eq. 145).301,302 BnO
BnO O O
O O
O
PMHS, Cp2Ti(OC6H4Cl-4)2 TBAF/alumina, MeC6H5, rt
OH (91%)
O
O
(Eq. 145)
ORGANOSILICON HYDRIDE REDUCTIONS
55
The reduction of an ester to the silylated acetal occurs with Et3 SiH/ Et2 NH/[RuCl2 (CO)3 ]2 (and other Ru catalysts) (Eq. 146),299 Et3 SiH/ (C6 F5 )3 B,281,282 or Ph3 SiH/(C6 F5 )3 B,115 and with Ph2 MeSiH/Mn(CO)5 C(O)Me.295 The latter system reduces methyl benzoate to toluene. An intramolecular version of the ester to silylated acetal transformation is effected with TBAF (Eq. 147).303,304 O OMe
OMe
MeC6H5, 100°, 16 h
SiMes2H CO2Et
O Et
OSiEt3
Et3SiH, EtI, Et2NH, [RuCl2(CO)3]2
(92%)
(Eq. 146)
Mes2Si O TBAF, 0°
O Et
OEt
O Et
(91%) dr = 98:2
(Eq. 147)
O Et
The reaction of lactones of benzyl alcohols with Et3 SiH/TFA results in complete reduction of the alcohol part of the lactone to the methylene group while preserving the carboxylate function (Eq. 148).305 O
CO2H
O Et3SiH, TiCl4
MeO
MeO (87%)
CH2Cl2, 0°
(Eq. 148)
OMe
OMe
The β-hydroxy ester resulting from the reaction of the tert-butyldimethylsilyl ketene acetal of ethyl acetate with a lactone under acid conditions can be reduced to the β-alkoxy ester.306 The overall yields are excellent (Eq. 149). OTBS O
O
1. OEt , SbCl5, TMSCl, SnI2, CH2Cl2, –78°, 30 min 2. Et3SiH, –23°, 2.5 h
OEt
O
(Eq. 149) O
(91%) cis:trans >99:1
The reaction of tert-butyl esters with Et3 SiH/TFA results in the reductive deprotection of the ester and formation of isobutane. The yields of the isobutane are not recorded, but the acids are obtained nearly quantitatively (Eq. 150).307 In a similar manner, the lactone shown in Eq. 151 is converted into the acid in good yield.308 In like manner, the reductive deprotection of allyl esters provides the carboxylic acids in high yields.270
56
ORGANIC REACTIONS
O t-BuO
N H
O
SBu-t H N
CO2Bu-t
Et3SiH, TFA CH2Cl2, rt, 15 min
O
O
CO2H + Me3CH
O (100%)
Et3SiH, TiCl4 CH2Cl2, –78°, 20 min
Ph
H2N
SBu-t H N
O
O Ph
O
(91%)
(Eq. 150)
(Eq. 151)
OH
The reduction of trifluoroacetates to alkanes occurs with the trifluoroacetates of benzylic and tertiary alcohols. This transformation is reported to occur with reagent combinations such as Ph3 SiH/nitrobenzene193 and EtCl2 SiH/AlBr3 .192 Secondary trifluoroacetates give more modest yields.192 Reduction of Aldehydes Reduction to Alcohols. Aldehydes do not normally react spontaneously with organosilicon hydrides to form alcohols. Exceptional behavior is displayed with organocobalt cluster complex carbonyl compounds, which form the corresponding alcohols (R = H, Me, Ph, etc.) after treatment with one equivalent of triethylsilane in refluxing benzene under a carbon monoxide atmosphere and acid workup (Eq. 152).309,310 Aside from these specific examples of anomalous behavior, the generally observed lack of reactivity is due to the combination of the relatively weak electrophilicity of the aldehyde carbonyl carbon center and the extremely feeble nucleophilicity of most tetravalent silyl hydrides. The reduction of aldehyde carbonyl groups by organosilicon hydrides can be promoted by several means. One way is by the introduction of acidic or electrophilic substances that coordinate with the carbonyl oxygen and thereby enhance the electrophilicity of the carbonyl carbon toward receiving a weakly nucleophilic silyl hydride. As mentioned previously, a second way is through the introduction into the reaction medium of substances possessing high nucleophilicity toward silicon centers. Such substances are thought to activate the silyl hydride by forming valenceexpanded silicon species with enhanced hydride-donating properties capable of attacking even weakly electrophilic centers such as the carbonyl groups of common aldehydes. Both means of promotion can be synthetically useful.
(CO)9Co3CCOR
1. Et3SiH, C6H6, CO 2. H2SO4 3. H2O
(CO)9Co3CCH(OH)R R = H (46%) R = Me (88%) R = Ph (68%)
(Eq. 152)
Promotion by Acid. In principle, the reduction of aldehydes to alcohols and alcohol derivatives by organosilicon hydrides should occur upon exposure to either Lewis or Brønsted acids, as represented in Eq. 2. In practice, although
ORGANOSILICON HYDRIDE REDUCTIONS
57
organosilicon hydride reductions of either aliphatic or aromatic aldehydes do occur rapidly under acid conditions, they are frequently complicated by the formation of other products. The reductions rarely give clean yields of alcohols when conducted under anhydrous conditions. The reaction of a mixture of 1-butanal and triethylsilane that occurs upon addition of excess trifluoroacetic acid is a typical example. Analysis of the reaction mixture immediately following the addition of acid shows the formation of 37% of di-n-butyl ether along with n-butyl alcohol and n-butyl trifluoroacetate in a combined yield of 58% (Eq. 153).311 No unreacted aldehyde remains. The same process transforms benzaldehyde into dibenzyl ether in 80% yield (Eq. 154).311,312 In both reactions, the silicon-containing products are triethylsilyl trifluoroacetate and hexaethyldisiloxane. The Et3 SiH/TFA combination can also lead to the trifluoroacetate and toluene derivatives when used with some aryl aldehydes.69 Et3SiH
n-C3H7CHO
(n-C4H9)2O + n-C4H9OH + n-C4H9O2CCF3 (37%) (58%)
TFA
CHO
Et3SiH
O
(80%)
TFA
(Eq. 153) (Eq. 154)
The reduction of aldehydes with the combination Et3 SiH/BF3 •OEt2 gives both the alcohol and the symmetrical ether,70 as do the Et3 SiH/TFA (and other acids) combinations.313 Addition of boron trifluoride etherate to a mixture of 1-octanal and triethylsilane leads to the formation of di-n-octyl ether in 66% yield and n-octyl alcohol in 34% yield (Eq. 155).74 n-C7H15CHO
Et3SiH BF3•OEt2
(n-C8H17)2O (34%) + n-C8H17OH (66%)
(Eq. 155)
The addition of water and a non-hydrogen-bonding solvent to the reduction medium causes the reactions to shift toward the formation of alcohol products.313 For example, triethylsilane in a mixture of concentrated hydrochloric acid and acetonitrile (5 : 4) reduces 1-heptanal to 1-heptanol in quantitative yield after 3 hours at room temperature. In a mixture of triethylsilane in sulfuric acid, water, and acetonitrile (2 : 2 : 5), n-heptanal gives a 97% yield of the same alcohol after 1.25 hours (Eq. 156).313 n-C6H13CHO
Et3SiH, H2O, MeCN H2SO4 or HCl
n-C7H15OH (97%)
(Eq. 156)
Triethylsilane reduces benzaldehyde to benzyl alcohol in 98% yield after 32 hours in a reaction medium containing sulfuric acid, water, and sulfolane (1 : 2 : 5) (Eq. 157). Neither benzene nor dimethylformamide is effective as an interfacing solvent for producing alcohol products under these conditions.313 CHO
Et3SiH, H2O H2SO4, sulfolane
OH
(98%)
(Eq. 157)
58
ORGANIC REACTIONS
In contrast to the propensity of Brønsted and some Lewis acids such as boron trifluoride etherate to promote the organosilicon hydride reduction of aldehydes to ethers under anhydrous conditions, uncomplexed boron trifluoride used with triethylsilane in dichloromethane solvent leads to the formation of primary alcohols in good yields from aliphatic aldehydes and from aromatic aldehydes containing electron-withdrawing groups.1 The success of this method depends on the absence of significant quantities of Brønsted acids in the reaction medium and requires that the boron trifluoride gas be scrubbed of hydrogen fluoride prior to introduction. Using this method, 1-undecanal gives a 92% isolated yield of 1-undecanol after only 10 minutes at 0◦ (Eq. 158). n-C10H21CHO
Et3SiH BF3, CH2Cl2
n-C11H23OH
(92%)
(Eq. 158)
The same technique causes the transformation of p-anisaldehyde (R = MeO) and p-cyanobenzaldehyde (R = CN) into the corresponding substituted benzyl alcohols in quantitative yields within 10 minutes at 0◦ (Eq. 159).1 The reduction of aryl aldehydes to benzyl alcohols without over-reduction to the arylmethanes also occurs with the reagent combinations PMHS/TBAF,278 PMHS/Triton B,278 and Ph3 SiH/(C6 F5 )3 B.116 The Ph3 SiH/(C6 F5 )3 B combination can be used to isolate the benzyl silyl ethers.282 Treatment of p-nitrobenzaldehyde (R = NO2 ) with a catalytic amount of the Lewis acid trimethylsilyl iodide (TMSI, generated in situ from trimethylsilyl chloride and sodium iodide) and tetramethyldisiloxane gives the benzyl alcohol in 91% isolated yield.314 CHO R
CH2OH
Et3SiH BF3, CH2Cl2 R MeO CN
R
(Eq. 159) (100%) (100%)
The reagent combinations PMHS/ZnCl2 ,315 PMHS/[Bu2 (AcO)Sn]2 O,316 and PMHS/HCuPPh3 317 all promote reduction of aldehydes to the corresponding alcohols in good yields. Trichlorosilane in dimethylformamide reduces aldehydes to alcohols in high yields.318 Promotion by Valence Expansion. Addition of nucleophilic substances to mixtures of aldehydes and organosilicon hydrides promotes the reduction of the carbonyl group as depicted previously in Eq. 6. The reductions can occur under homogeneous83 or heterogeneous79,80,319 conditions, both with83,320 and without solvent.83,319 When the reactions occur under anhydrous conditions with catalytic amounts of nucleophile, the first-formed product is frequently a silyl ether. This ether can be regarded as an intermediate that normally undergoes facile acidor base-catalyzed hydrolysis to give a final alcohol product (Eq. 160).80 The silicon-containing products are usually silanols and/or disiloxanes produced by
ORGANOSILICON HYDRIDE REDUCTIONS
59
hydrolysis of the intermediate silyl ethers. These reductions are normally quite chemoselective and tolerate many other functional groups. R3SiH + R'CHO
Nu–
R3SiOCH2R
H2O
(R3Si)2O + R3SiOH + R'CH2OH
R = H, alkyl, aryl R' = alkyl, alkenyl, aryl
(Eq. 160)
Fluoride ion is effective in promoting the reduction of aldehydes by organosilicon hydrides (Eq. 161). The source of fluoride ion is important to the efficiency of reduction. Triethylsilane reduces benzaldehyde to triethylbenzyloxysilane in 36% yield within 10–12 hours in anhydrous acetonitrile solvent at room temperature when tetraethylammonium fluoride (TEAF) is used as the fluoride ion source and in 96% yield when cesium fluoride is used.83 The carbonyl functions of both p-anisaldehyde and cinnamaldehyde are reduced under similar conditions. Potassium bromide or chloride, or tetramethylammonium bromide or chloride are not effective at promoting similar behavior under these reaction conditions.83 Moderate yields of alcohols are obtained by the KF-catalyzed PMHS, (EtO)3 SiH, or Me(EtO)2 SiH reduction of aldehydes.80,83,79 ArCHO + Et3SiH
F– MeCN
ArCH2OSiEt3
Ar = Ph (36-96%)
(Eq. 161)
Diphenylsilane reacts with two equivalents of neat n-heptanal in the presence of anhydrous cesium fluoride within three minutes at room temperature to form di-n-heptoxydiphenylsilane quantitatively (Eq. 162).319 Potassium fluoride and potassium phthalate are considerably less effective promoters, even at temperatures up to 140◦ .319 2 n-C6H13CHO + Ph2SiH2
CsF
(n-C7H15O)2SiPh2 (100%)
(Eq. 162)
Alkoxy-substituted organosilicon hydrides are more reactive toward carbonyl functions in the presence of nucleophiles than are organosilicon hydrides that have only alkyl or aryl substituents at the silicon center. The order of reactivity of the silanes used is (EtO)3 SiH > (EtO)2 SiMeH, and that of the fluoride salts is CsF > KF.83 The use of these silane/fluoride salt pairs can lead to some very chemoselective transformations.79,80,319 For example, after hydrolytic workup, an equimolar mixture of benzaldehyde, diethoxymethylsilane, and cesium fluoride gives an 80% yield of benzyl alcohol after only 10 minutes at room temperature under heterogeneous conditions.80 The use of triethoxysilane and potassium fluoride gives a 90% yield of benzyl alcohol after six hours at room temperature. The same combination of reagents converts 1-heptanal into 1-heptanol in 70% yield within four hours without affecting benzophenone or 1,3-diphenylpropan-2-one when either is added to the same reaction mixture (Eq. 163).83 n-C6H13CHO + (EtO)3SiH
1. KF 2. H2O
n-C7H15OH
(70%)
(Eq. 163)
60
ORGANIC REACTIONS
These reaction conditions also permit the chemoselective quantitative reduction of benzaldehyde to benzyl alcohol without any concomitant reduction of either acetophenone or 3,3-dimethylbutan-2-one present in the same reaction mixture.83 Additionally, this useful method permits the reduction of aldehyde functions in polyfunctional compounds without affecting amide, anhydride, ethylenic, bromo, chloro, or nitro groups.79,80,319 An improved variation of this reduction method involves the use of potassium fluoride (either anhydrous or as the dihydrate) or potassium formate in a polar aprotic solvent such as dimethylformamide or dimethyl sulfoxide in conjunction with either diethoxymethylsilane or PMHS. The intermediate silyl ethers are worked up by acidic hydrolysis when diethoxymethylsilane is used and by methanolysis when PMHS is the reducing agent.82 A high chemoselectivity among carbonyl group reductions may be accomplished using this method by adjusting the reaction conditions. Aldehydes are especially easy to reduce this way. The combination of diethoxymethylsilane and KF in dimethylformamide produces a 90% yield of benzyl alcohol from benzaldehyde in 0.25 hour at 20◦ following workup.82 In a similar way, 1-heptanal forms 1-heptanol in 85% yield within 1.75 hours at 10◦ . Other combinations of the salts, solvents, and organosilicon hydrides give useful, if somewhat lower, yields of products. Potassium fluoride dihydrate, although a more active catalyst than the anhydrous salt, requires use of an excess of organosilicon hydride because the water that is present destroys some of the silane. Use of potassium formate and PMHS in dimethylformamide permits facile selective reduction of both alkyl and aryl aldehydes in the presence of ketones and esters.82 The system of Me(EtO)2 SiH and KO2 CH is very selective toward the reduction of aldehydes in the presence of ketones.82 In a similar approach aldehydes are reduced with [HSi(OEt)4 ]K.288 Fluoride ion catalyzes the hydrosilylation of both alkyl and aryl aldehydes to silyl ethers that can be easily hydrolyzed to the free alcohols by treatment with 1 M hydrogen chloride in methanol.320 The most effective sources of fluoride are TBAF and tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF). Somewhat less effective are CsF and KF. Solvent effects are marked. The reactions are facilitated in polar, aprotic solvents such as hexamethylphosphortriamide (HMPA) or 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H )-pyrimidinone (DMPU), go moderately well in dimethylformamide, but do not proceed well in either tetrahydrofuran or dichloromethane. The solvent effects are dramatically illustrated in the reaction of undecanal and dimethylphenylsilane to produce undecyloxyphenyldimethylsilane. After one hour at room temperature with TBAF as the source of fluoride and a 10 mol% excess of silane, yields of 91% in HMPA, 89% in DMPU, 56% in dimethylformamide, 9% in tetrahydrofuran, and only 1% in dichloromethane are obtained (Eq. 164).320 TBAF n-C10H21CHO + PhMe2SiH
rt
n-C11H23OSiMe2Ph
(1-91%)
(Eq. 164)
The reduction of aldehydes to alcohols takes place under mild conditions upon treatment with a mixture of trimethoxysilane and lithium methoxide (20 mol%
ORGANOSILICON HYDRIDE REDUCTIONS
61
excess of each) in diethyl ether at room temperature (Eq. 165). The reaction occurs with both alkyl and aryl aldehydes and can be used to reduce aldehydes in the presence of ketones, esters, and nitriles. Workup is by treatment with 1 M aqueous hydrochloric acid.91 For example, benzaldehyde forms benzyl alcohol in 85% isolated yield within 20 hours under these conditions, whereas onitrobenzaldehyde and p-anisaldehyde give the corresponding alcohols in yields of 55 and 86%, respectively. 1-Octanal yields 1-octanol in 80% yield after just six hours.91 Triethoxysilane and diethoxymethylsilane are not as effective as reducing agents as trimethoxysilane. Sodium methoxide, alkali metal ethoxides, and, especially, potassium methoxide also are effective nucleophilic promoters. Lithium and sodium pinacolates are strong promoters that cause the reduction of both aldehydes and ketones.91 RCHO + (MeO)3SiH
MeOLi RCH2OH
Et2O, rt
R = n-C7H15 (80%) R = Ph (85%) R = 2-O2NC6H4 (55%) R = 4-MeOC6H4 (86%)
(Eq. 165)
There seems little doubt that the active reducing agents in these kinds of reductions are pentavalent hydridosilicates. In fact, it is possible to produce the stable potassium salts of these species in high yield by reacting equivalent amounts of the appropriate trialkoxysilanes and potassium alkoxides in large amounts of tetrahydrofuran or 1,2-dimethoxyethane (DME) at room temperature (Eq. 166).107 A variety of alkoxy groups may be used (R = Et, i-Pr, Ph), but neither lithium nor sodium alkoxides are effective in this reaction.107 Potassium tetraethoxyhydrosilicate shows high reducing properties toward both aldehydes and ketones without the need for added catalysts (Eq. 167).288 It reduces benzaldehyde to benzyl alcohol in 90% yield and 1-pentanal to 1-pentanol in 80% yield following aqueous acid workup.288 (RO)3SiH + ROK R = Et, i-Pr, Ph
THF or DME
[(EtO)4SiH]– K+ + RCHO
[(RO)4SiH]– K+
1. THF, 0° or rt 2. H3O+
(80-90%)
RCH2OH R = n-Bu (80%) R = Ph (90%)
(Eq. 166)
(Eq. 167)
A similar reducing system is created by combining dilithium catecholate and trichlorosilane at −78◦ in tetrahydrofuran. It is speculated that the relatively unstable pentacoordinate bis(1,2-benzenediolato)hydridosilicate (61) is formed in situ and that it is this species that can reduce aldehydes and ketones, but not esters, to alcohols when they are added to the reaction mixture at 0◦ (Eq. 168).93 In a like manner, the dilithium salt of 2,2 -dihydroxybiphenyl, which forms a pentacoordinate intermediate that is stable enough to react at room temperature, can also be used to promote the reduction reaction. The alkoxides of aliphatic diols
62
ORGANIC REACTIONS
such as 1,2-ethanediol and pinacol are not very effective as ligand promoters in this system and those of simple alcohols are without effect. Use of the dilithium catecholate/trichlorosilane combination gives benzyl alcohol from benzaldehyde in 96% yield within two hours. Substitution of 2,2 -dihydroxybiphenyl for catechol provides a 92% yield of 2,2-dimethylpropanol from 2,2-dimethylpropanal within five hours at room temperature.93 OLi + HSiCl3
2 OLi
THF –78°
1. RCHO, 0° 2. H2O
OHO Si O O 61 RCH2OH
–
(Eq. 168) R = t-Bu (92%) R = Ph (96%) R = 4-MeC6H4 (96%)
Chemoselectivity between aldehydes and ketones is demonstrated by this method in the competitive reduction of a mixture of pentanal and cyclohexanone. The ratios of primary and secondary alcohols are 75 : 25 when catechol is used at 0◦ and 79 : 21 when 2,2 -dihydroxybiphenyl is used at room temperature. These regents are not as chemoselective as other reducing agents such as LiAlH(OBu-t)3 (87 : 13) and LiAlH(OCEt3 )3 (94 : 6) at 0◦ .93 Several types of organosilicon hydrides are effective reducing agents toward carbonyl functions because of valence expansion produced by intramolecular effects. Aryl silyl hydrides with amine functions are especially prone to having the proper configuration to permit such intramolecular valence expansion.321,322 The valence expanded silicon hydrides compounds 58–60 react spontaneously with both p-nitrobenzaldehyde and p-anisaldehyde to give, within 0.5 to 3 days, the respective benzyl alcohols in quantitative yields following aqueous acidic workup.321 Under the same conditions, a mixture of α-naphthylphenylsilane and N ,N -dimethylbenzylamine fails to react even after 17 days.321 It is of interest to note that the silyl hydrides 58, 59, and 60 (Eqs. 136 and 137) all have trigonal bipyramidal structures in which the active hydrogens occupy equatorial positions. Compound 58 is such an effective carbonyl reducing agent that it reduces carbon dioxide to formaldehyde via a stable silylformate intermediate.323 The 10-Si-5-hydridosiliconate ion 62 is known in association with lithium,323 tetrabutylammonium,101 and bis(phosphoranyl)iminium93 cations. It is synthesized by hydride addition to the 8-Si-4-silane 63, which is derived from hexafluoroacetone.101 Benzaldehyde and related aryl aldehydes are reduced by solutions of 62 in dichloromethane at room temperature101 or in tetrahydrofuran at 0◦ 96 within two hours. The alkyl aldehyde, 1-nonanal, is also reduced by 62 in tetrahydrofuran at 0◦ .96 Good to excellent yields of the respective alcohols are obtained following hydrolytic workup. The reactions are not accelerated by addition of excess lithium chloride,96 but neutral 63 catalyzes the reaction, apparently through complexation of its silicon center with the carbonyl oxygen prior to delivery of hydride from 62.101
ORGANOSILICON HYDRIDE REDUCTIONS
CF3 CF3
–
CF3 CF3
O Si H
O Si
O CF3 62
63
O CF3 63
CF3
CF3
The solid bases CaO and hydroxyapatite catalyze the hydrosilylation of benzaldehyde by triethoxysilane at 90◦ in yields of 59% and 72% within one and two hours, respectively.323,324 These reductions also very likely involve activation by valence expansion of the silicon hydride reagent. Reductive Amidation of Aldehydes. The reductive amidation of aldehydes using an organosilane as the reducing agent has been realized. Benzaldehyde reacts over a 74-hour period with triethylsilane and acetonitrile in 75% aqueous sulfuric acid at room temperature to produce an 80% isolated yield of N benzylacetamide (Eq. 169).313 Octanal fails to react under the same conditions.313 Reductive amidation of aldehydes also occurs with the reagent combination Et3 SiH/TFA/primary amide (Eq. 170).326 CHO + MeCN
CHO HO2C
aq. H2SO4
NHCOMe
Et3SiH
(80%)
(Eq. 169)
Ph
(Eq. 170)
O Et3SiH, TFA, PhCONH2
N H
MeC6H5, 120°, 18 h
(96%)
HO2C
Reductive Esterification. Aldehydes can give ester products when treated with combinations of organosilicon hydrides and carboxylic acids that have appreciable basicity. Benzaldehyde gives a product mixture consisting of 12% dibenzyl ether and 88% of benzyl formate when it is treated for 8 hours at room temperature with a slight excess of triethylsilane in formic acid.313 p-Nitrobenzaldehyde produces 33% bis(p-nitrobenzyl) ether and 66% of p-nitrobenzyl trifluoroacetate when it reacts with Et3 SiH/TFA for 5 hours at room temperature. Other aldehydes give small, variable amounts of esters under similar reaction conditions. Although this general approach to the synthesis of esters from aldehydes is an attractive one, it appears not yet to be optimized for maximum synthetic utility because of the frequent formation of considerable amounts of ether products (Eq. 171).313 RCHO + R'CO2H R = alkyl, aryl R' = H, CF3, Cl2CH
Et3SiH
(RCH2)2O + RCH2O2CR' (variable)
(Eq. 171)
64
ORGANIC REACTIONS
Reductive Etherification. As indicated earlier, aldehydes as well as ketones often give very good yields of ethers when they are treated with Brønsted acids or other electrophilic species in the presence of organosilicon hydrides (Eq. 172). In the absence of added alcohols, symmetrical ethers are obtained. RCHO
R'3SiH
(Eq. 172)
(RCH2)2O
HX
When alcohols are added to the reaction mixture, unsymmetrical ether products may be obtained. Starting with a mixture of aldehydes can also give rise to the formation of unsymmetrical ethers. These ether products are formed under conditions different from those used in the formation of ethers directly from alcohols. Thus, it is postulated that the reaction sequence that leads from the carbonyl substrate to the ether involves the intermediate formation of hemiacetals, acetals, or their protonated forms and alkoxycarbenium ions, which are intercepted and reduced to the final ether products by the organosilicon hydrides present in the reaction mix. The probable mechanistic scheme that is followed when Brønsted acids are present is outlined in Scheme 2.311,327,328 RCH=O + H+ R = alkyl, aryl RCH=OH+ + RCH2OH +
RCH=OH+ H H R C OCH2R + OH R'3SiH
RCHOCH2R
R'3SiH
RCH2OH +
RCHOCH2R + H2O
RCH2OCH2R
R = alkyl, aryl
Scheme 2
Reduction of aldehydes to symmetrical ethers can be accomplished in good to excellent yields with Et3 SiH/Ph3 C+ ClO4 − ,329 Et3 SiH/ZnCl2 ,330 Me2 ClSiH/ In(OH)3 ,331 Et3 SiH/BiCl3 ,332 (HMe2 Si)2 O/TMSOTf (or TMSCl/NaI),314 Et3 SiH (or PhMe2 SiH)/Bu4 NClO4 ,333 Et3 SiH/TMSOTf,334 Et3 SiH/H2 SO4 ,328 and Et3 SiH/ TFA.313 The reaction of 1.4 equivalents of triethylsilane with two equivalents of trifluoroacetic acid rapidly reduces benzaldehyde to dibenzyl ether in 80% yield at temperatures below 40◦ .311 Similar treatment of n-butanal with two equivalents of triethylsilane and three equivalents of trifluoroacetic acid produces di-n-butyl ether in a more modest 37% yield.311 Variations of these simple reaction conditions permit greater yields of desired ether products to be obtained. For example, 1heptanal reacts with a 10 mol% excess of triethylsilane to give a 90% yield of di-n-heptyl ether within 45 minutes at room temperature when the reaction is run in a twenty-fold excess of trifluoroacetic acid acting as solvent.313 With the exception of p-nitrobenzaldehyde, which gives only a 33% yield of the symmetrical ether (the remainder is converted into p-nitrobenzyl trifluoroacetate), other representative aryl aldehydes normally give yields of symmetrical ethers on the order of 80% or greater.313
ORGANOSILICON HYDRIDE REDUCTIONS
65
Unsymmetrical ethers may be produced from the acid-promoted reactions of aldehydes and organosilicon hydrides when alcohols are introduced into the reaction medium (Eq. 173).327,328 An orthoester can be used in place of the alcohol in this transformation.327,335 A cyclic version of this conversion is reported.336 Treatment of a mixture of benzaldehyde and a 10 mol% excess of triethylsilane with methanol and sulfuric, trifluoroacetic, or trichloroacetic acid produces benzyl methyl ether in 85–87% yields.328 Changing the alcohol to ethanol, 1-propanol, 2-propanol, or 1-heptanol gives the corresponding unsymmetrical benzyl alkyl ethers in 45–87% yield with little or no side products.328 A notable exception is the tertiary alcohol 2-methyl-2-propanol, which requires 24 hours.328 1-Heptanal gives an 87% yield of n-heptyl methyl ether with added methanol and a 49% yield of benzyl n-heptyl ether with added benzyl alcohol under similar conditions.328 RCHO + R"OH R = alkyl, aryl R'' = alkyl
R'3SiH
RCH2OR"
HX
(45-87%)
(Eq. 173)
R' = aryl
The yield of ethyl n-pentyl ether formed from the reduction of 1-pentanal by Et3 SiH/TFA in ethanol is 57% after 6–8 hours at 50–60◦ .327 The yield of product increases to 72% when one equivalent of ethyl orthoformate and some anhydrous hydrogen chloride are added to the reaction medium.327 Presumably, this reduces the amount of free water in the reaction medium. An interesting and effective variation of this general synthetic approach uses electrogenerated acid (EG acid) to assist in the formation of ethers from aldehydes.333 This method permits the synthesis of both symmetrical and unsymmetrical ethers. The experiments are conducted using platinum electrodes in a simple undivided cell. A mixture of aldehyde and a 20 mol% excess of either triethylsilane or dimethylphenylsilane in dichloromethane solvent containing lithium perchlorate and tetra-n-butylammonium perchlorate is electrolyzed by the passage of small amounts of current (0.04–0.45 Faradays/mol) to give symmetrical ethers (Eq. 174). In this way, both dibenzyl and dialkyl ethers may be produced in excellent yields (86–96%).333 Unsymmetrical ethers are produced in 50–99% yields when alkoxytrimethylsilanes are added to the reaction mixture (Eq. 175).333 The alkoxy groups can include allyl, propargyl, and 3-phenylpropyl moieties. Phenol trimethylsilyl ether is ineffective in producing phenyl ethers.333 RCHO R = alkyl, Ph PhCHO + TMSO
R'3SiH EG acid
RCH2OCH2R
(86-96%)
(Eq. 174)
R' = Me, Et, Ph Et3SiH, EG acid, CH2Cl2, rt
Ph
O
(95%)
(Eq. 175)
Various chemical species with Lewis acid properties are also effective in promoting the direct conversion of aldehydes into ethers by organosilicon hydrides.
66
ORGANIC REACTIONS
They offer the advantage that reductions can be effected under conditions that permit the conversion of substrates that may be adversely sensitive to the presence of strong Brønsted acids. For example, in the presence of a 10% excess of triethylsilane, addition of one-half equivalent of boron trifluoride etherate to octanal results, within one hour, in the formation of a 66% yield of dioctyl ether after a basic hydrolytic workup. Benzaldehyde provides a 75% yield of dibenzyl ether under the same reaction conditions. The remainder of the mass is found as the respective alcohol.70 Zinc chloride is also capable of catalyzing this reaction. With its use, simple alkyl aldehydes are converted into the symmetrical ethers in about 50% yields.330 Superior yields of ethers from aldehydes are obtained by the use of several other electrophilic species. The addition of 5 mol% of trityl perchlorate to a mixture of triethylsilane and 3-phenylpropanal in dichloromethane at 0◦ produces an 83% yield of bis-(3-phenylpropyl) ether within 10 minutes (Eq. 176).329 Reductive polycondensation of isophthalaldehyde occurs with two equivalents of triethylsilane in the presence of 10 mol% of trityl perchlorate to give 40–72% yields of polyether with average molecular weights ranging from 6,500 to 11,400 daltons (Eq. 177).337 Addition of one equivalent of an alkoxytrimethylsilane to the reaction mixture produces unsymmetrical ethers in good to excellent yields. Thus, a mixture of (E)-cinnamaldehyde, 3-phenylpropoxytrimethylsilane, and triethylsilane in dichloromethane reacts under the influence of a catalytic amount of trityl perchlorate to give the unsymmetrical ether in 88% yield (Eq. 178).329 Ph3C+ClO4–
O Bn
H
OHC
CHO
O
Bn
Et3SiH, CH2Cl2, 0°
Ph3C+ClO4–
Bn
—OCH2
(Eq. 176)
(83%)
CH2—
Et3SiH, CH2Cl2
(Eq. 177)
n
(40-72%) +
Ph
CHO + Ph
OTMS
Ph3C ClO4
–
Et3SiH, CH2Cl2, 0°
Ph
O
Ph
(88%)
(Eq. 178) The use of trimethylsilyl-based electrophilic catalysts with organosilicon hydrides also promotes the conversion of aldehydes into ethers and avoids the need to employ the potentially hazardous trityl perchlorate salt.314,334,338 One reagent pair that is particularly effective in the reductive conversion of aldehydes into symmetrical ethers is a catalytic amount of trimethylsilyl triflate combined with either trimethylsilane, triethylsilane, PMHS,334 or 1,1,3,3tetramethyldisiloxane (TMDO, 64) as the reducing agent (Eq. 179).314 Either Me Me H Si O Si H Me Me 64
ORGANOSILICON HYDRIDE REDUCTIONS
67
dichloromethane or benzene can be used as the solvent. The reactions occur at temperatures ranging from 0◦ to 80◦ . These conditions produce symmetrical ethers from both aromatic and aliphatic aldehydes in yields frequently exceeding 90%. Aromatic aldehydes tend to give minor amounts of benzyl alcohols as byproducts.334 The synthesis of cyclic ethers from dialdehydes or keto aldehydes is also possible (Eqs. 180 and 181).339 (HMe2Si)2O
RCHO
TMSOTf or TMSI
(RCH2)2O
(Eq. 179)
R = alkyl, aryl
O O
Et3SiH, TMSOTf
Ph Et3SiH, TMSOTf
O
O
CH2Cl2, rt, 45 min
CH2Cl2, rt, 45 min
(92%)
(Eq. 180)
(71%)
(Eq. 181)
Ph O
O
The formation of unsymmetrical ethers from the reduction of aldehydes in the presence of tetrahydropyran (THP) ethers is reported (Eq. 182).340 O O
OTHP
+ PhCHO
Et3SiH, TMSOTf MeCN, 0°, 1 h
O O
OBn (90%)
(Eq. 182) Trimethylsilyl iodide can be substituted for the trimethylsilyl triflate catalyst in the reactions of aliphatic aldehydes. TMSI can be generated conveniently in situ either from trimethylsilyl chloride and sodium iodide in acetonitrile314 or from hexamethyldisilane and iodine in dichloromethane334 or pentane.338 It is noted that neither triisopropylsilane nor PMHS is an effective reducing agent for this purpose when used with TMSI under these conditions.314,334 Equivalent amounts of aldehydes and alkoxytrimethylsilanes react to form unsymmetrical ethers in near quantitative yields in the presence of either trimethylsilane or triethylsilane and catalytic amounts (ca. 10 mol%) of TMSI in dichloromethane.329,333,334,341 The procedure is particularly convenient experimentally when trimethylsilane is used with TMSI because the catalyst provides its own color indicator for the reduction step (color change from deep violet to vivid red-gold) and the only silicon-containing product following aqueous workup is the volatile hexamethyldisiloxane (bp 99–100◦ ). It is possible to introduce trimethylsilane (bp 7◦ ) either as a previously prepared solution in dichloromethane or by bubbling it directly into the reaction mixture. Cyclohexyloxytrimethylsilane and n-butanal react by this method to give a 93% isolated yield of n-butyl cyclohexyl ether (Eq. 183).334
68
ORGANIC REACTIONS OC4H9-n
OTMS 1. TMSH, TMSI, CH2Cl2
n-C3H7CHO +
(93%)
2. H2O
(Eq. 183)
Trimethylsilane in pentane is a particularly good system for the TMSIcatalyzed reductive coupling of tertiary alkoxytrimethylsilanes with aldehydes to form sterically crowded tertiary-primary ethers.337 In this way, 1-(tertbutoxymethyl)-3-methylbenzene is formed in 87% yield (Eq. 184).338 Reaction of terephthaldehyde with two equivalents of the trimethylsilyl ether of 1adamantanol under these conditions leads to a good yield of the diadamantyl ether of 1,4-benzenedimethanol (Eq. 185).338 CHO
CH2OBu-t
TMSH
+ t-BuOTMS
(87%)
(Eq. 184)
TMSI, n-C5H12 OHC
TMSH, TMSI, n-C5H12
+ 2
OTMS
CHO
–78° to rt, 5-6 h
(Eq. 185)
O (78%)
O
Cyclic ethers can also be formed in a fashion similar to that of the reactions described previously (Eq. 186),306,342 and also result from the reductive etherification of bis(trimethylsilylated) diols and dialdehydes (Eq. 187).343 O OTMS
H Ph H + O
2. Et3SiH, –23°, 2.5 h
OTMS
O
H
1. SbCl5, TMSCl, SnI2, CH2Cl2, –78°, 30 min
TMSO
Ph
O
O
(76%)
(Eq. 186)
O
Et3SiH, BiBr3, CH2Cl2
(7%)
MeCN, –30° to 0° O
O
(Eq. 187) The reductive silylation of aldehydes provides a one-step route to silyl ethers. This is accomplished with the reagent combinations PhMe2 SiH/CuH(PPh3 ),317 Et3 SiH/ZnCl2 (or SnCl2 or NiCl2 ),343 Ph2 SiH2 /CsF (or KF, BnMe3 NF, KO2 CH),75,319 Et3 SiH/(C6 F5 )3 B,115,281 PhMe2 SiH/CsF,320,345 – 347 and Et3 SiH/ TBAF.76 Montmorillonite clay that has been subjected to ion exchange with ferric ion catalyzes the hydrosilylation of benzaldehyde with triethylsilane to give benzyl triethylsilyl ether in 79% yield.324,325
ORGANOSILICON HYDRIDE REDUCTIONS
69
Various non-conjugated diene aldehydes react with Et3 SiH/Ni(cod)2 /PPh3 to give O-triethylsilylated cycloalkanols in low to high yields. Acyclic dienes can lead to the silylated cycloalkanols in moderate yields with the proper catalyst (Eq. 188).348 Bicyclic systems are also generated by this methodology (Eq. 189).349 MeO2C
CHO
PhMe2SiH, Ni(cod)2
OSiEt3
MeO2C
MeO2C
+
MeO2C P Ph, THF, rt, 5 h
OSiEt3
MeO2C
(Eq. 188)
MeO2C (61%) 7.3:1
H
Et3SiH, Ni(cod)2, PPh3
OSiEt3 (81%)
THF, 30°, 4 h
CHO
(Eq. 189)
H
Et3 SiH/Ni(cod)2 brings about the reaction of an aldehyde and an alkyne to provide the silylated allyl alcohol (Eq. 190).350 The reaction also occurs in an intramolecular mode. CHO
Et3SiH, Ni(cod)2
+
Ph
Et3SiO Ph
:
Mes N
H Ph
(84%)
(Eq. 190)
N Mes
Reduction to Alkanes. Carbonyl groups can be reductively deoxygenated to methylene functions if both of the two steps represented by Eqs. 1 and 2 proceed to completion. With aldehydes, this process leads to the transformation of the CHO group into a CH3 group. The relative instability of primary alkyl carbenium ions in the condensed phase and the weak intrinsic nucleophilicity of organosilicon hydrides are the reasons that primary alkyl alcohols are not reduced to hydrocarbons. For these same reasons, aliphatic aldehydes do not undergo complete deoxygenation to methylterminated hydrocarbons when treated with acids and organosilicon hydrides under usual laboratory conditions. In contrast, many aryl aldehydes can be transformed into methylarenes by this method. Since the organosilane reduction of benzyl alcohols to the corresponding toluene derivatives is known, it is not surprising that the reduction of an aryl aldehyde to a toluene is possible. This transformation has been carried out with Et3 SiH/TFA,69,351,352 (EtO)3 SiH, and Et3 SiH with various catalysts,353 Et3 SiH/(C6 F5 )3 B,281 PMHS/Pd/C,316 and PMHS/ (C6 F5 )3 B.354 The last combination also reduces alkyl aldehydes to the corresponding alkanes (Eq. 191).281,282,354 CHO
PMHS, (C6F5)3B CH2Cl2, rt, 5-20 min
(90%)
(Eq. 191)
70
ORGANIC REACTIONS
Trifluoroacetic acid solutions of benzaldehydes having electron-donating ring substituents form the corresponding methyl arenes when at least two equivalents of an organosilicon hydride are added to the solution at room temperature. The reaction conditions permit preservation of the integrity of functions such as halogen, alkoxy, carboxylate, cyano, and nitro. There is little difference in the reducing abilities of triethylsilane, tri-n-propylsilane, and tri-n-hexylsilane in these reactions. Thus, the silane reducing agent can be chosen that best suits purification of the desired product. Basic aqueous workup converts the silicon reaction products derived from the organosilicon hydride into the corresponding silanols and disiloxanes, which may be removed from the desired reduction products by simple distillation.69 Benzaldehyde itself forms no toluene; only dibenzyl ether and benzyl trifluoroacetate are formed. Triethylsilane (2.2 equivalents) causes the transformation of p-anisaldehyde into p-methylanisole in 76% yield after only 30 minutes. Use of a three-fold excess of dimethylphenylsilane in place of the triethylsilane results in a slight improvement in yield to 83% after 45 minutes.69 Similar treatment of a trifluoroacetic acid solution of p-tolualdehyde with triethylsilane gives only a 20% yield of p-xylene after 11 hours reaction time followed by basic workup. Use of 2.5 equivalents of dimethylphenylsilane enhances the yield to 52% after only 15 minutes. This reaction proceeds stepwise through the formation of a mixture of the trifluoroacetate and the symmetrical ether. These intermediates slowly form the desired p-xylene product along with Friedel-Crafts side products under the reaction conditions (Eq. 192).73 Addition of co-solvents such as carbon tetrachloride or nitromethane helps reduce the amount of the Friedel-Crafts side products.73 CHO
R3SiH
O
O2CCF3
+
TFA
(Eq. 192) R3SiH
+
TFA
Friedel-Crafts products
Treatment of a polyfunctional chromium-tricarbonyl-complexed hydroxy aldehyde with an excess of Et3 SiH/TFA for 4.5 hours gives an 82% yield of fully reduced product with both the formyl and hydroxy groups completely and selectively reduced (Eq. 193).352 OHC MeO HO Cr(CO)3
Et3SiH, CH2Cl2 TFA, 0° to 60°
(82%)
(Eq. 193)
MeO Cr(CO)3
The sequence of reagent and substrate addition can be quite important in these reactions. For example, a trifluoroacetic acid solution of 2,4,6-trimethylbenzaldehyde forms isodurene in 98% yield within 15 minutes when 2.2 equivalents of triethylsilane are added to the reaction mixture at room temperature.69 In
ORGANOSILICON HYDRIDE REDUCTIONS
71
contrast, when trifluoroacetic acid is added to a stirred solution of triethylsilane and 2,4,6-trimethylbenzaldehyde, isodurene is formed in only 70% yield after basic aqueous workup. Minor side products under these reaction conditions are mesitylene (formed via acid-catalyzed decarbonylation of the aldehyde) and the Friedel-Crafts product 2,4,6,2 ,3 ,4 ,6 -heptamethyldiphenylmethane (Eq. 194).311 CHO Et3SiH
+
TFA (70%)
+
(5%)
CH2
(Eq. 194)
(8%)
The Et3 SiH/BF3 •OEt2 combination fails to cause complete deoxidative reduction of aldehydes, forming instead mixtures of primary alcohols and symmetrical ethers.74 By contrast, aryl aldehydes lacking electron-withdrawing ring substituents, when reacted in dichloromethane with at least two equivalents of triethylsilane and gaseous boron trifluoride at 0◦ , form the corresponding methylarenes within a few minutes (Eq. 195).1 Even benzaldehyde produces a 52% yield of toluene by this method when 18 equivalents of triethylsilane are added to suppress formation of Friedel-Crafts oligomers. The method offers the advantage that fluorotriethylsilane is formed, which is volatile and is easily separated from the desired organic products.1 ArCHO
Et3SiH, CH2Cl2 BF3, 0°
ArMe + Et3SiF Ar = Ph (52%) Ar = 4-MeC6H4 (45%) Ar = 4-ClC6H4 (68%) Ar = 4-MeOC6H4 (100%)
(Eq. 195)
If Friedel-Crafts products are desired, a clever method exists for the direct conversion of aryl aldehydes into diarylmethanes. Reaction of a mixture of an aromatic aldehyde and a catalytic amount of trimethylsilyl trifluoromethanesulfonate and excess polymethylhydrosiloxane in either benzene or toluene at reflux results in the formation of the respective arylphenyl or tolylmethanes in reasonably good yields within 1–3 hours (Eq. 196).314 Thus, benzaldehyde reacts in refluxing benzene containing a few drops of TMSOTf and excess PMHS to give diphenylmethane in 92% yield within two hours and in refluxing toluene within one hour to give a 95% yield of a mixture of phenyl-p-tolylmethane and phenyl-o-tolylmethane in a 70 : 30 ratio. p-Tolualdehyde gives a 60% yield of phenyl-p-tolylmethane when heated at reflux in benzene for 2.5 hours and an 80% yield of di-p-tolylmethane and p-tolyl-o-tolylmethane in a 90 : 10 ratio when heated at reflux in toluene for 30 minutes. o-Chlorobenzaldehyde gives a mixture of 25% phenyl-o-chlorophenylmethane and 55% of bis(o-chlorophenyl)ether, and p-chlorobenzaldehyde gives a 65% yield of a mixture of phenyl-p-chlorophenylmethane and bis(p-chlorophenyl)ether in a 75 : 25 ratio when heated at reflux in benzene for 3 hours.314
72
ORGANIC REACTIONS
ArCHO + Ar'H
PMHS
ArCH2Ar'
TMSOTf
(25-95%)
(Eq. 196)
Ar = Ph, 4-MeC6H4, 4-ClC6H4, 2-ClC6H4 Ar' = Ph, 4-MeC6H4
The TFA-catalyzed triethylsilane reductive condensation of an aldehyde with indoles provides a convenient route to 3-substituted indoles in modest to good yields (Eq. 197).355 Cl H
CO2Et
+
O
CO2Et N Ph
Cl
Et3SiH, TFA
(79%) N
Ph
Ph
Ph
(Eq. 197) Reduction to Methylene Halides. Treatment of aryl aldehydes with selected organosilicon hydrides and an appropriate trimethylsilyl halide produces benzyl chlorides, bromides, and iodides directly in good to excellent yields by reductive halogenation (Eq. 198). This protocol offers the advantage of being simple and leading only to the monohalo derivatives. The method is specific for the carbonyl group of both aryl ketones and aldehydes and preserves the integrity of many other groups (e.g. ring halogen, alkyl, alkoxy, cyano, nitro, hydroxy, ester) that may be found in polyfunctional compounds. Alkyl aldehydes form symmetrical ethers instead of halides under these reaction conditions.314,356,357 Several variations of this general method exist. In the most straightforward approach for synthesizing iodides, the addition of an external trimethylsilyl reagent is not required. Aromatic aldehydes normally react within minutes at room temperature with iodine and TMDO in dichloromethane solution to produce benzyl iodides in high yields (66–87%) (Eq. 199). A reactive silyl iodide is believed to be formed in situ from tetramethyldisiloxane and iodine under these conditions. The reaction is not limited to aryl rings with only electron-donating groups; chloro-, hydroxy-, alkyl-, alkoxy-, cyano-, and carboalkoxy-substituted rings all undergo the transformation.357 The same transformation can be carried out with diiodosilane.358 TMDO ArCHO
TMSX
ArCH2X
(40-97%)
(Eq. 198)
Ar = various substituted aryl CH2I
CHO TMDO
(87%)
I2, CH2Cl2, rt OH
OH
(Eq. 199)
ORGANOSILICON HYDRIDE REDUCTIONS
73
Another variation of this method involves the treatment of an acetonitrile solution of the aryl aldehyde, trimethylsilyl chloride, and either sodium iodide, if iodide products are desired, or lithium bromide, if bromide products are desired, with TMDO. After an appropriate reaction time (5–195 minutes) at a temperature in the range of −70◦ to 80◦ , the upper siloxane layer is removed and the benzyl iodide or bromide product is isolated from the remaining lower portion after precipitation of the inorganic salts by addition of dichloromethane. For example, p-anisaldehyde reacts to form p-methoxybenzyl bromide in 84% isolated yield under these conditions (Eq. 200).314,356 CHO
TMDO, MeCN
MeO
CH2Br
TMSCl, NaBr
(Eq. 200)
(84%) MeO
In the preparation of iodides, but not bromides, PMHS may be substituted for the TMDO. Chlorides can be obtained if thionyl chloride and zinc iodide are added to suppress the formation of symmetrical ethers.314 An example of this type of reductive chlorination is shown by the TMDO-mediated conversion of ptolualdehyde into p-methylbenzyl chloride (Eq. 201).313 To obtain chlorides from aldehydes having electron-withdrawing groups such as nitro or carbomethoxy, the initial reaction is first carried out at −70◦ and the mixture is then heated to reflux in order to reduce the formation of symmetrical ether by-products. Zinc chloride is substituted for zinc iodide for the synthesis of chlorides of substrates with electron-donating groups such as methoxy and hydroxy.314 CHO
TMDO, TMSCl
Cl
SOCl2, ZnI2 (cat.)
(Eq. 201)
(87%)
Reductive Amination. Reaction of an aminohydrodimethylsilane with aldehydes in the presence of a Lewis acid catalyst gives the corresponding amine in good to high yields (Eq. 202).359 The use of an Et3 SiH/TFA/amine reagent combination also leads to the reductive amination of aldehydes (Eq. 203).360 Comparable reductive aminations of aldehydes are possible in moderate yields with PhSiH3 /Bu2 SnCl2 /amine,361,362 and in good yields with PMHS/TiCl4 /amine363 or with amine/Cl3 SiH.364 CHO
Et2NSiHMe2, TiCl4
NEt2
CH2Cl2, 0° to rt, 36 h
CHO NH N
CN
Et3SiH, TFA, CH2Cl2 N H
Ph
SO2Pr-n
CN
SO2Pr-n
+
(Eq. 202)
(91%)
Ph
N
rt, 2-4 h NH N (90%)
(Eq. 203)
74
ORGANIC REACTIONS
Reductive Thiolation. Treatment of aldehydes with triethylsilane, thiols, and boron trifluoride monohydrate6,217 yields sulfides in a one-flask process. For example, this method gives a 97% yield of benzyl isopropyl sulfide from benzaldehyde and 2-propanethiol (Eq. 204).365 PhCHO
1. i-PrSH, BF3•OH2, CH2Cl2, 0°, 1 min 2. Et3SiH, 0° to rt, 3 h
Ph
(97%)
SPr-i
(Eq. 204)
Reduction of Ketones The selective organosilane reduction of ketone functions can be effected in the presence of a number of other functional groups including epoxides,320,366 ketals,86,367 thioketals,368 other ketones,369,370 β-lactams,371 alkynes,372 esters,79,80,83,84,87,320,373,374 α-bromides,76,80,83 amides80,83,84,86,276,320,375 84,276 83,376 83,86 ureas, trifluoroacetamides, sulfonamides, and nitro groups.80 Reduction to Alcohols. The organosilane-mediated reduction of ketones to secondary alcohols has been shown to occur under a wide variety of conditions. Only those reactions that are of high yield and of a more practical nature are mentioned here. As with aldehydes, ketones do not normally react spontaneously with organosilicon hydrides to form alcohols. The exceptional behavior of some organocobalt cluster complex carbonyl compounds was noted previously. Introduction of acids or other electrophilic species that are capable of coordination with the carbonyl oxygen enables reduction to occur by transfer of silyl hydride to the polarized carbonyl carbon (Eq. 2). This permits facile, chemoselective reduction of many ketones to alcohols. Certain catalysts promote the reduction of ketones with organosilanes. The reduction of acetophenone with Et3 SiH is catalyzed by the diphosphine 65 and gives only a small amount of overreduction to ethylbenzene.377 Aryl alkyl enones and ynones are reduced to the corresponding alcohols with triethoxysilane and the titanium-based catalyst 66.378 Trichlorosilane reduces acetophenone in 90% yield with N -formylpyrrolidine catalysis.379 O
O
O
N
N PPh2
Ph2P 65
O Ti
O
O
66
Ph
Ph (dimer)
Promotion by Acid. The same range of Lewis and Brønsted acids that promote the silane reduction of aldehydes can be used for the reduction of ketones. These acid-catalyzed reductions appear to proceed by direct hydride transfer rather than by a single-electron transfer mechanism.380 Similar to the case of aldehydes, the silane reductions of ketones promoted by Brønsted acids rarely give clean yields of alcohols when conducted under anhydrous conditions. Instead, mixtures of alcohols, esters, and silyl ethers often result.313,381 The reagent combination of Et3 SiH/HCl (or H2 SO4 ) gives good yields of the alcohol, although
ORGANOSILICON HYDRIDE REDUCTIONS
75
by-products of the sym-ether among others can complicate the reduction.313 Use of zinc chloride to promote organosilicon hydride reduction of ketones to siloxanes that can be hydrolyzed to alcohols is well known. It is one of the first Lewis acid catalysts reported to be useful for this purpose,382,383 although others are known.384 The combination of Et3 SiH/TFA/NH4 F provides a good yield of the alcohol with some ether formation.135 High yields of the alcohol from both aryl and alkyl ketones are realized by the HMDS/(AcOBu2 Sn)2 O316 and HMDS/Sn(OTf)2 385 reagent combinations. The Et3 SiH/(C6 F5 )3 B combination cleanly reduces aryl ketones to the substituted benzyl alcohols.116 Under certain conditions, the trifluoroacetic acid catalyzed reduction of ketones can result in reductive esterification to form the trifluoroacetate of the alcohol. These reactions are usually accompanied by the formation of side products, which can include the alcohol, alkenes resulting from dehydration, ethers, and methylene compounds from over-reduction.68,70,207,208,313,386 These mixtures may be converted into alcohol products if hydrolysis is employed as part of the reaction workup. An example is the reduction of cyclohexanone to cyclohexanol in 74% yield when treated with a two-fold excess of both trifluoroacetic acid and triethylsilane for 24 hours at 55o and followed by hydrolytic workup (Eq. 205).203 O
OH 1. Et3SiH, TFA
(Eq. 205)
(74%)
2. aq. K2CO3
Promotion by Valence Expansion. As in reactions of aldehydes, addition of nucleophilic substances to mixtures of ketones and organosilicon hydrides promotes reduction of the carbonyl group as depicted in Eq. 6. Ketones are conveniently reduced in high yields with reagent combinations of (EtO)3 SiH or Me(EtO)2 SiH and KF (or CsF).80 The pentacoordinate silane 67 itself reduces ketones in high yields (Eq. 206).84 In a somewhat similar approach, the lithium salt of silicate 68 is a good reducing agent for ketones (Eq. 207).96 Other hydridosilicates are known to similarly reduce ketones.93 O
SiPhH2 NMe2
+
OH rt, 12 h
(100%)
(Eq. 206)
(88%)
(Eq. 207)
67 CF3
CF3
O O
OH +
Li+ H
–
THF, 0°, 2 h
Si O
CF3
CF3 68
76
ORGANIC REACTIONS
The PMHS/TBAF system provides both an excellent and practical approach to the reduction of aryl ketones to the benzyl alcohols.278 Similarly, the PMHS/ TritonB combination gives high yields of the benzyl alcohols.278 Diastereoselective Reductions. The diastereoselectivity of organosilane reductions of ketones has been the topic of a number of studies. Extensive studies of the Brønsted acid promoted reductions of alkyl-substituted cyclohexanones by mono-, di-, and trialkylsilanes show that chain branching and other steric features of both the silane and the carbonyl substrate can be important factors in determining the isomeric compositions of reduction product mixtures.68,381,384,386 In general, the reduction of various substituted cyclohexanones does not show effective diastereoselectivity even when very sterically hindered silanes such as Ph3 SiH387,388 or (t-Bu)3 SiH386 are employed. A quite good system is a silane under TritonB or TBAF catalysis.278 The best system for the trans-selective reduction of 4-tert-butylcyclohexanone is the sterically encumbered (TMSO)3 SiH/TBAF (Eq. 208).278 This system is not successful in the stereoselective reduction of 2-methylcyclohexanone, giving a cis:trans selectivity of 18 : 82, although 3-methylcyclohexanone gives a cis:trans ratio of 7 : 93 and a high (>90%) yield of 3-methylcyclohexanol. The combination of PMHD/dibutylacetoxytin oxide (DBATO) reduces 4-tertbutylcyclohexanone exclusively to trans-4-tert-butylcyclohexanol.316 The active reducing agent in this system is likely a tin hydride species. A system of Ph2 MeSiH (or Ph3 SiH)/TBAF/HMPA reduces 2-methylcyclohexanone in a cis:trans ratio of 95 : 5.320 Only cis-2-methylcyclohexanol is isolated from the reduction of 2-methylcyclohexanone with Ph3 SiH/(C6 F5 )3 B.116 Other systems give only moderate selectivities in the reduction of substituted cyclohexanones.70,79,93,116,278,313,367,381,382,384,386,389 – 392 t-Bu
t-Bu (TMSO)3SiH, TBAF
t-Bu (99%)
+
(1%)
OH
O
(Eq. 208)
OH
Naphthoquinone is reduced to 1,2,3,4-tetrahydronaphthalene with Et3 SiH/TFA in 60% yield.393 Quinones can be reduced to hydroquinones in good yields with hydridosiloxanes such as TMDO with iodide present (Eq. 209).314,316,357 The reductive dehydration of a 1,3-diketone leads to an enone (Eq. 210).374 O
OH Et3SiH, TFA
(Eq. 209)
(60%)
60-65°, 10 h O
OH
O
O Ph2SiH2, (Ph3P)4RhH CH2Cl2, rt, 12 h O
O
(46.6%)
+
(2.5%)
(Eq. 210)
ORGANOSILICON HYDRIDE REDUCTIONS
77
Reduction of the ketone carbonyl of cis-1,2,3,4,4a,9b-hexahydro-8-hydroxydibenzofuran-3-one with trifluoroacetic acid and triethylsilane at 0◦ produces a mixture of the α- and β-isomers of the C3 alcohol with an α : β ratio of 1 : 4 (Eq. 211).394 This result can be compared with the isomer ratio of 100 : 1 that results when sodium borohydride is used as the reducing agent.394 The same cis pair of alcohol isomers is formed in 77% combined yield, but in a reversed ratio of α : β = 4 : 1, when the less saturated tetrahydrodibenzofuran analog is used as the substrate (Eq. 212).394 HO
HO
H O O H
HO
H
Et3SiH
H
TFA
OH
O H
H OH
+ O H
H
1:4
(Eq. 211) HO
HO Et3SiH O
TFA
HO
H H OH
O H
O
H OH
+ O H
(Eq. 212)
H
(77%) 4:1
Treatment of a pentacyclic 1α,11-(2-oxethano) thioketal steroid with excess Et3 SiH/TFA causes reduction of the carbon-carbon double bonds as well as the 17-carbonyl group to give a single reaction product (Eq. 213).368 Other work utilizes trifluoroacetic acid, triethylsilane, and anisole in the presence of a catalytic amount of boron trifluoride etherate to reduce the acetyl carbonyl of a 3-acetyl2-azetidinone derivative with a dr of 8 : 1 (Eq. 214).395 O O
O
OH
H
1. xs Et3SiH, TFA, CH2Cl2
(73%)
2. H2O, OH–
S
H
S S
S
H
(Eq. 213) O
HO
H H OBn N
O
Et3SiH, BF3•OEt2
OBn
TFA, PhOMe, –10°
DAM DAM = (4-MeOC6H4)2CH
HO
H H
OBn
N O
H H
+ N
DAM
O
(Eq. 214)
DAM
(71%) 8:1
In a similar way, a mixture consisting of 2% boron trifluoride etherate in trifluoroacetic acid and triethylsilane brings about the regioselective reduction of the acyclic carbonyl group of the diketovinyl chloride shown in Eq. 215 in high yield (>94%), but with formation of approximately equal amounts of the two possible diastereomers formed from the creation of a new chiral center.396
78
ORGANIC REACTIONS Cl
Cl
O
OH
Et3SiH
OH
+
TFA, 2% BF3 • OEt2
O CO2Me
Cl
O CO2Me
O CO2Me
(79%) 1:1
(Eq. 215) The stereoselective reduction of the carbonyl group of β-hydroxy ketones can be accomplished by a silylation-intramolecular reduction sequence. The best results are obtained when diisopropylchlorosilane is employed.397 The clever use of an intramolecular hydride transfer from a pre-anchored silyl hydride site allows β-hydroxy ketones to be reduced to 1,3-diols with a very high degree of diastereoselectivity.397 – 399 A specific example is the reaction of the hydroxy ketone shown in Eq. 216, first with chlorodiisopropylsilane to form the acyclic siloxane and then with a Lewis acid catalyst to cause intramolecular hydride transfer with formation of a pair of cyclic trans- and cis-disiloxanes. The respective anti- and syn-diols are obtained after fluoride ion catalyzed hydrolysis. The trans:cis ratio of the disiloxane intermediates varies with the Lewis acid employed: TiCl4 (30 : 1), MgBr2 •OEt2 (60 : 1), SnCl4 (120 : 1), and BF3 •OEt2 (320 : 1).397 – 399 A similar reduction with chlorodimethylsilane also gives good results (Eq. 217).400 OH O
i-Pr
Pr-i
i-Pr
Si O
+
O
SiH(Pr-i)2 O
SnCl4, CH2Cl2
Pr-i Si
O
O
(i-Pr)2SiHCl
O
OH OH
aq. HF
OH OH +
MeCN (67%), anti:syn = 120:1
(Eq. 216) O Ph
OSiMe2H Ph
OH OH
1. TBAF, THF, –78°, 3.5 h 2. aq. HCl
Ph
Ph
(76%)
(Eq. 217)
The diastereoselectivity of the reduction of α-substituted ketones has been the subject of much investigation. The reagent combination of trifluoroacetic acid and dimethylphenylsilane is an effective method for the synthesis of erythro isomers of 2-amino alcohols, 1,2-diols, and 3-hydroxyalkanoic acid derivatives.86,87,276,375 Quite often the selectivity for formation of the erythro isomer over the threo isomer of a given pair is >99 : 1. Examples where high erythro preference is found in the products are shown below (Eqs. 218–220).276 Similar but complementary results are obtained with R3 SiH/TBAF, where the threo isomer product
ORGANOSILICON HYDRIDE REDUCTIONS
79
predominates (Eqs. 221 and 222).86,87,320 The threo isomer also predominates with the PMHS/TBAF system (Eq. 223).401 O NHCO2Et
Ph O
CO2Me
Ph O
O2CPh
Ph
OH
PhMe2SiH, TFA
NHCO2Et
Ph
0°, 2.5 h
(Eq. 218)
OH
PhMe2SiH, TFA
(Eq. 219)
O2CPh
(Eq. 220)
OH
OH
PhMe2SiH, TFA
(87%)
CO2Me
Ph
0°, 3 h
0°, 6 h
(87%)
O2CPh
Ph
+
Ph
(72%) 93:7 O Ph
HMPA, rt, 12 h
OH
OH
PhMe2SiH, TBAF
NMe2
NMe2
Ph
+
NMe2
Ph
(Eq. 221)
(83%) 95%)
2. P(OEt)3 HO
O
OTr
O
(Eq. 286)
OTr
Reduction of α,β-Unsaturated Esters The reduction of the C=C bond of α,β-unsaturated esters has been carried out with various silane/catalyst combinations. The combination of Et3 SiH/ RhCl(PPh3 )3 gives the silyl ketene acetal along with the silylated hemiacetal, the result of the 1,2-reduction of the carbonyl group (Eq. 287).466 The use of other silanes in this transformation gives similar results. Acrylates give hydrosilylation of the C=C bond, leading to β-silyl esters and their silyl ketene acetals as the major products (Eq. 288).466,467 O
Et3SiH, ClRh(PPh3)3 OEt
C6H6, 80°, 2 h
OSiEt3
OSiEt3 OEt (74%)
+
OEt (6%)
(Eq. 287)
94
ORGANIC REACTIONS Et3SiH, ClRh(PPh3)3
O OEt
OSiEt3
O +
C6H6, 70°, 3 h
Et3Si
Et3Si
OEt (52%)
OEt
(Eq. 288)
(28%)
Triethoxysilane and RhH(PPh3 )4 produce the silyl ketene acetal in high yield.374 Methyl acrylate is reduced to methyl propionate with Cl3 SiH/CoCl2 448 or PMHS/Pd-nanocomposite catalyst,219 and to a mixture of methyl propionate, the methyl β-silylpropionate, and the methyl α-silylpropionate with R3 SiH/H2 PtCl6 or R3 SiH/RhCl(PPh3 )3 where R = Me, Et, or n-Pr.467 The reduction of ethyl acrylate shows similar behavior.451,466 The combination of Et3 SiH/Mo(CO)6 works well for the conjugate reduction of α,β-unsaturated esters.450 This method appears to be free of some of the side reactions mentioned above. The use of metallic nickel, triphenylphosphine, and phenylsilane reduces α,β-unsaturated esters to the saturated esters in moderate yields.438 Dimethylphenylsilane carries out the same transformation in the presence of CuCl.444,445 Triethylsilane and trifluoroacetic acid can reduce α,β-unsaturated esters in good yields468 as can Et3 SiH/TMSOTf.469 Excellent yields of the silane reduction of α,β-unsaturated esters are obtained by the reaction of PMHS and sodium tert-butoxide in the presence of catalyst 73 (Eq. 289).454 O Ph
O
PMHS, 73, NaOBu-t OEt
CN
Ph
OEt CN (93%) dr = 1.5:1
MeC6H5, t-BuOH, rt, 4 h Pr-i N
i-Pr
(Eq. 289)
N
Pr-i CuCl Pr-i 73
The Ph2 SiH2 /AlCl3 reduction of β-sulfonyl-α,β-unsaturated esters results in the formation of the β-sulfonyl ester. Good yields are obtained and AlCl3 is the best Lewis acid catalyst for this reaction (Eq. 290).373 Ts S
CH2Cl2, 20°, 15 h CO2Me
Ts
Ph2SiH2, AlCl3 S
(86%)
(Eq. 290)
CO2Me
In the reductive aldol condensation of an α,β-unsaturated ester and an aldehyde shown in Eq. 291, the initial step is believed to be the addition of an in situ formed rhodium hydride to the α,β-unsaturated ester, followed by reaction of the resulting rhodium enolate with the aldehyde.470 The reaction has been carried out both inter-470 and intramolecularly471,472 as well as in an asymmetric fashion (Eq. 291).
ORGANOSILICON HYDRIDE REDUCTIONS O
OSiEt3
Et3SiH, RhH(PPh3)4 H
95
OSiEt3
CO2Pr-i +
MeC6H5, 50°, 16 h CO2Pr-i
CO2Pr-i
(20%)
(40%)
(Eq. 291) Similarly, methyl methacrylate reacts with ketones and TMSH/RuCl3 •3H2 O to give β-trimethylsiloxy-2,2-dimethyl methyl esters in good yields. A lactone example is shown in Eq. 292.473 Methyl acrylate, trans methyl (E)-cinnamate, and 3,4-dehydro-δ-lactone react in an analogous manner, albeit in lower yields.473 O O
+
TMSH, RhCl3•3 H2O, rt
O
TMSO
O
O
(Eq. 292)
(34%)
Allyl acrylates have been reacted with the combination of ClMe2 SiH/ [(cod)RhCl]2 /Me-DuPHOS (1,2-bis(2,5-dimethylphospholano)benzene) to bring about reduction of the α,β-unsaturated ester followed by a Claisen rearrangement to the γ ,δ-unsaturated carboxylic acid (Eq. 293).474 Other silanes did not perform as well in this sequence. O
O MeCl2SiH, [(cod)RhCl]2
O
O
MeDuPhos, C6H6, rt, 15 h
O
O
(Eq. 293)
HO2C (50%) dr = 23:1
In yet another example of an in situ reductive generation of an enolate, βamido esters are formed via the reaction of an α,β-unsaturated ester with a silane in the presence of an isocyanate (Eq. 294).475 The yields obtained using methyl acrylate and methyl crotonate as substrates are generally excellent.
CO2Me
Et2MeSiH, [Rh(cod){P(OPh) 3}2]OTf PhNCO, CH2Cl2, 45°, 13 h
Ph
H N
(Eq. 294)
CO2Me (88%) O
The organosilane reduction of pentafluorophenyl acrylate in the presence of an imine was shown to lead to β-lactams in good yields (Eq. 295).476 The conversion of an ethyl ynoate into an E-ethyl enoate in high yield is shown in Eq. 296.477 Et2MeSiH, [Ir(cod)Cl]2, P(OPh)3, CH2Cl2, 18 h
O OC6F5
N
PhN
O
Ph H
(Eq. 295) (80%) trans:cis >20:1
96
ORGANIC REACTIONS OH
OH CO2Et
TBSO
(EtO)3SiH, CH2Cl2 Cp*Ru(NCMe)3PF6
NMe2
CO2Et NMe2
TBSO
O
(Eq. 296)
O (92%)
Reduction of α,β-Unsaturated Amides The conjugate hydrosilylation of α,β-unsaturated amides can be carried out in high yields with PhSiH3 /Mo(CO)6 (Eq. 297)450 or Ph2 SiH2 /ZnCl2 /Pd(PPh3 )4 .436 Primary, secondary, and tertiary amides are equally reactive.450 The reduction of a β-tributylstannyl-α,β-unsaturated tosylamide is also reported.469 O
PhSiH3, Mo(CO)6 NH2
O NH2
THF, reflux, 1.7 h
(Eq. 297)
(100%)
Reduction of α,β-Unsaturated Nitriles The reaction of α,β-unsaturated nitriles with organosilanes in the presence of Wilkinson’s catalyst gives the α-silyl nitriles in good yields (Eq. 298).466 The PhSiH3 /Mo(CO)6 combination reduces α,β-unsaturated nitriles to the nitriles in good yields, although the β,β-disubstituted 3-methylcrotonitrile does not react.450 Cinnamonitrile is reduced to the saturated nitrile in good yield with PMHS/Pdnanocomposite219 and in only modest yield with Ph2 SiH2 /ZnCl2 /Pd(PPh3 )4 .436 The ferrocenyl unsaturated nitrile shown in Eq. 299 is reduced with Et3 SiH/TFA in good yield.179 The PhSiH3 /Co(dpm) reductive aldolizations of an α,βunsaturated nitrile and an aldehyde also occur in good yields (Eq. 300).478
CN
PhMe2SiH, ClRh(PPh3)3
CN
60°, 4 h
SiPhMe2
(87%)
CN
CN Et3SiH, TFA, rt, 3 h
Fe
Fe
(83%)
CN CHO +
(Eq. 298)
(Eq. 299)
CN
CN
OH
PhSiH3, Co(dpm)2 ClCH2CH2Cl, 20°, 12 h
OH
+ CN
Ph (70%)
(5%)
(Eq. 300)
ORGANOSILICON HYDRIDE REDUCTIONS
97
Reduction of Acetals, Ketals, Hemiacetals, Hemiketals, and Orthoesters The ketals of both aryl and alkyl ketones can be reduced to the methylene derivatives in good yields (Eqs. 301 and 302).479
O Ph
1. Et3SiH, SnBr2–AcBr, CH2Cl2, rt, 24 h
O
MeO
OMe
1. Et3SiH, SnBr2–AcBr, CH2Cl2, rt, 24 h
(Eq. 301)
(Eq. 302)
(67%)
2. (n-Bu)3SnH, AIBN, C6H6, reflux, 0.5 h
Ph
(77%)
Ph
2. (n-Bu)3SnH, AIBN, C6H6, reflux, 0.5 h
Ph
Simple dimethylacetals and ketals are reduced with the Et3 SiH/acid combination where the acid catalyst can be TMSOTf,339,480 – 482 BF3 •OEt2 ,483 – 485 TFA,327,486 Nafion-H,335 tin-montmorillonite,353 FSO3 H/BSA,487 TiCl4 ,488 – 492 AlCl3 /HCl,146 and FSO3 H/BSU.487 Of these, Nafion-H, BF3 •OEt2 , BSA, and TMSOTf all give excellent isolated yields of the corresponding ether. The 1, 3-propanediol acetals of acetophenone and benzaldehyde are reduced to monoortho-benzyldiols with PhSiH3 /RhCl(PPh3 )3 (Eq. 303),493 Et3 SiH/TFA,494 Et3 SiH/BF3 •OEt2 ,495 or PMHS/AlCl3 (Eq. 304).496 Ph O
PhSiH3, RhCl(PPh3)3
O
THF, rt, 48 h
Ph
Ph
PMHS, AlCl3
O O
N3
Et2O, CH2Cl2, rt, 12 h
O
OH
(89%)
(Eq. 303)
N3 (69%)
(Eq. 304)
BnO HO 7
7
This reduction technique also applies to the benzaldehyde acetals of sugars with reduction of the benzaldehyde acetals taking place in preference to reduction of the anomeric acetal (Eq. 305).497 Ph
O O BnO
OBn O BnO OMe
Et3SiH, BF3•OEt2 CH2Cl2, rt, 4 h
HO BnO
O
(83%)
(Eq. 305)
BnO OMe
A highly useful and important regioselective reduction of substrate 84 leads to a mixture of 3-hydroxy ethers 85 and 86 in a 32 : 1 ratio (Eq. 306). Compound 85 is further converted to the anti-influenza drug oseltamivir phosphate, better known as Tamiflu.498
98
ORGANIC REACTIONS
Et
O
Et
O
Et
CO2Et Et3SiH, TiCl4 CH2Cl2, –34°, 2-6 h
Et
OMs 84
CO2Et
O
HO
+
HO
Et
OMs 85
CO2Et
Et
(56%) 32:1
O OMs 86
(Eq. 306) The triethylsilane reduction of the peroxy ethyl ether shown in Eq. 307 takes place at the C–O bond of the methyl ether without reduction of either the iodide or the peroxide functionalities (Eq. 307).499 In contrast, a bridged peroxy ether undergoes reduction of both C–O bonds of the peroxide linkage rather than at the ether bridge (Eq. 308).499 MeO
H
O O
Et3SiH, HOTf
O O I
I
(Eq. 307)
H
H O
(56%)
Et3SiH, HOTf
O
O
O
(51%)
(Eq. 308)
single unidentified diastereomer
The Et3 SiH/tetracyanoethylene combination reduces acetals and ketals to the corresponding ethers but the yields are mixed.500 The full reduction of benzaldehyde acetals to the toluene derivatives is realized by the initial reduction with Et3 SiH/SnBr2 –AcBr followed by Bu3 SnH/AIBN (azobis(isobutyronitrile)) or LiAlH4 .479 The overall yields are excellent. Diphenylmethylsilyl-protected hemiacetals are reduced upon treatment with Ph2 SiH2 /Mn(CO)3 Ac.295 Et3 SiH/TiCl4 reduces tert-butyldimethylsilyl ketals.306 The combination of TBSH/Sn(OTf)2 and a silyl ether converts ethylene glycol acetals and ketals into ethers (Eq. 309).501 Ph O
O
TBSH, n-C6H13OTMS Sn(OTf)2, MeCN, –20°, 3-6 h
Ph
OC6H11-n
(86%)
(Eq. 309)
α-Trimethylsilyloxythianes are reduced to the respective thianes with Et3 SiH/ TMSCl/InCl3 (Eq. 310).426,502 Trimethylsilane with TMSI or TMSOTf effects this conversion as well.392 OTMS Ph
SEt
Et3SiH, TMSCl, InCl3 CH2Cl2, rt, 5 h
Ph
SEt
(68%)
(Eq. 310)
A number of conditions are available for the reduction of the anomeric acetals to the reduced sugars. Among these are the combinations Et3 SiH/BF3 •OEt2 / TFA483 and Et3 SiH/TMSOTf,503,504 although some isomerization is found to
ORGANOSILICON HYDRIDE REDUCTIONS
99
occur with this latter system. The polysaccharide shown in Eq. 311 is converted into the the deoxysugar in good yield.483 MeO O O
MeO
MeO
MeO AcO MeO
1. Et3SiH, BF3•OEt2, TFA, 0° 2. Ac2O, rt, 24 h
O
O
(81%)
MeO
(Eq. 311)
6
Diiodosilane reduces acetals to alkyl iodides in a reductive iodination reaction (Eq. 312).358,505 Alkyl bromides are formed from the reductive bromination of benzaldehyde acetals with the combination Et3 SiH/SnBr2 .506 O
I2SiH2, CH2Cl2, rt, 4 h
O
I
CHO
CHO
(Eq. 312)
(94%)
There is a report of a reductive amination of an acetal. Thus, (Et2 N)Me2 SiH/ TiCl4 reacts with the dimethylacetal of benzaldehyde to form benzyldiethylamine in good yield (Eq. 313).359 OMe
Et2NSiHMe2, TiCl4
OMe
NEt2
CH2Cl2, 0° to rt, 36 h
(79%)
(Eq. 313)
Hemiacetals and hemiketals also undergo reduction to ethers with organosilanes under acid catalysis. These reductions generally occur in good yield. They are carried out with Et3 SiH/BF3 •OEt2 ,497,507 – 512 Et3 SiH/TFA,162,513 – 516 PhMe2 SiH/TMSOTf,517 and Et3 SiH/TMSOTf,518,519 which prove especially useful for sugar systems. The combination of Ph3 SiH/TiCl4 reduces hemiketals in the presence of a dithioketal (Eq. 314).520 S S Ph
O OH
S
Ph3SiH, TiCl4
S
CH2Cl2, –78°, 5 min
Ph
(72%)
(Eq. 314)
O
The PhSiH3 /RhCl(PPh3 )3 combination reduces trimethyl orthobenzoate to the dimethyl acetal of benzaldehyde with small amounts of methyl benzyl ether product (Eq. 315).493 Ph
OMe OMe OMe
PhSiH3, RhCl(PPh3)3 PPh3, 60°, 48 h
OMe Ph OMe (80%)
+
OMe
(Eq. 315)
Ph (7%)
Reduction of Aminals and Hemiaminals As demonstrated with acetals and ketals, aminals are also readily reduced with silanes under acid catalysis. The Et3 SiH/BF3 •OEt2 combination reduces
100
ORGANIC REACTIONS
aminals to the amines in excellent yields (Eq. 316).521 – 523 A similar reduction with Et3 SiH/TFA occurs in equally high yield (Eq. 317).524 Hemiaminals are reduced with Et3 SiH/TFA (Eq. 318).525 TBSO
TBSO Et3SiH, BF3•OEt2 N Ac
OMe
N Ac
CO2Me
CO2Me Et3SiH, TFA
N
N H Me HO
rt, 4 h
O
N
N H Me H
CHCl3, rt, 20 h
N
(79%)
(Eq. 317)
O
Et3SiH, TFA
MeO2C
(Eq. 316)
(97%)
CH2Cl2, –40°, 1-2 h
(63%)
MeO2C
(Eq. 318)
N Me
OH
Amidoaminals and amidohemiaminals are reduced to the amides with organosilanes and an acid catalyst. Best among the reported reagent combinations are Et3 SiH/TiCl4 ,524 and Et3 SiH/BF3 •OEt2 .521 Et3 SiH/TFA526 (Eq. 319) and Et3 SiH/ BF3 •OEt2 527 are effective in reducing amidoaminals in high yields. O
O N H
OH
Et3SiH, TFA
NHMe
CHCl3, rt, 1-4 h
MeO
(91%)
(Eq. 319)
MeO
N -Trimethylsilyloxymethylimines can be reduced to the corresponding N alkylimines with Et3 SiH/BF3 •OEt2 (Eq. 320).522 OTMS CF3
Ph
Et3SiH, BF3•OEt2
Ph
N
CH2Cl2, 50°, 24 h
Ph
CF3
(61%)
N
(Eq. 320)
Ph
O-Aminomethyl lactones are reduced to amino acids with the Et3 SiH/TFA combination (Eq. 321).528 Fmoc N
O O
Et3SiH, TFA CHCl3, rt, 22 h
Fmoc N O Me OH
(98%)
(Eq. 321)
Reduction of Enamines Enamines are reduced to amines in good yields with Et3 SiH/TFA.529 – 533 This reagent combination causes a variety of indoles to undergo stereoselective cis
ORGANOSILICON HYDRIDE REDUCTIONS
101
reduction of the indole ring while other potentially reducible functional groups in the molecule are unaffected (Eq. 322).534 The organosilane reduction of enamides proceeds in excellent yields with the Et3 SiH/TFA reagent system (Eq. 323).524,535 H N
O
H N
O NPh
NPh Et3SiH, TFA
N
N
50°, 64 h MeO
(58%)
(Eq. 322)
MeO N H
MeO
H N
Br
OEt O
MeO
N H
MeO
H N
Br
Et3SiH, TFA
OEt (99%)
–10°, 0.5 h
(Eq. 323)
O
MeO
The enamide double bond is reduced in preference over that of the enone moiety in each of the two examples shown below (Eqs. 324 and 325).536,537 Other enamides are reduced under similar conditions.235,537,538 O
O Et3SiH, TFA, CH2Cl2
Cl
N CO2Me
N
O
(56%)
Cl
(Eq. 324)
N CO2Me
N O
O
0°, 6 h; then rt, 6 h
Et3SiH, TFA, CHCl3
O O
20°, 24 h
(75%)
(Eq. 325)
O
Reduction of Imines The reduction of imines with organosilanes is reported to take place with the reagent combinations PMHS/ZnCl2 ,539 Et3 SiH/TFA,540,541 Cl3 SiH,318,542 PMHS/ butyltin trioctanoate,543 PhSiH3 ,544 Et3 SiH/HCO2 H,208 PhMe2 SiH/TFA,276 Cl3 SiH/BF3 •OEt2 ,545 Et3 SiH (and related silanes)/RhCl(PPh3 )3 ,546 and Cl2 SiH2 .545 Imines are reduced in high yields with various silanes in the presence of Wilkinson’s catalyst or PdCl2 .120 Triethylsilane and diethylsilane are the most effective reducing agents. Diimine 87 undergoes reduction of the imine functions with diethylsilane without reduction of the amide functionality, even though the amide carbonyl is in the more reactive α-heteroaryl position (Eq. 326).547
102
ORGANIC REACTIONS O Cl
O
N
Cl
N
Et2SiH2, RhCl(PPh3)3
N N Ph
87
CH2Cl2, rt, 16 h N Ph
O Cl
O
N
Cl
N N
HN Ph
(81%)
NH Ph
(Eq. 326)
Reduction of Oximes Oximes can be reductively converted into the Boc-protected primary amines in good yields with the combination of PMHS/(Boc)2 O/Pd/C (Eq. 327).548 OBenzyloxyimines549 are reported to be reduced in good to excellent yields by this method. O HO
O
O
PMHS, (t-BuCO)2O 10% Pd/C, 40-50°, 6 h
N
Boc
OMe
O
O
(85%)
H N
(Eq. 327)
OMe
O
O-Benzoyloximes are nicely reduced to O-benzoylhydroxylamines with Et3 SiH/TFA (Eq. 328).550,551 O-Acetyloximes are reduced with Et3 SiH/TMSOTf in moderate to high yields.552 The diethylphosphatoimine 88 is reduced to the hydroxylamine derivative.553 BzO
BzO
N
NH
Et3SiH, TFA, 40°, 12 h
O P OEt EtO 88
O P OEt EtO
(79%)
(Eq. 328)
Reduction of Nitroalkanes The combination PMHS/Pd/C reduces nitrobenzenes to anilines in high yields (Eq. 329),316 as does Et3 SiH/RhCl(PPh3 )3 (Eq. 330).554 This latter combination can also reduce both nitro and enone functionalities.554 NO2
PMHS, Pd/C
NH2
EtOH, 80° O O
O2N
O O
Et3SiH, RhCl(PPh3)3 O
(Eq. 329)
(89%)
MeC6H5, reflux, 4 h
O H2N
(Eq. 330)
ORGANOSILICON HYDRIDE REDUCTIONS
103
Tertiary nitro alkanes or activated nitro groups are reduced to the alkane with loss of the nitro group by a combination of PhSiH3 and catalytic amounts of (n-Bu)3 SnH and 1,1 -azobis(cyclohexanecarbonitrile) (ACHN), even in the presence of other potentially reducible functional groups.555 The examples shown in Eqs. 331 and 332 illustrate this behavior.555 PhSiH3, (n-Bu)3SnH, ACHN
NO2 CN O
NO2
CN O
PhSiH3, (n-Bu)3SnH, ACHN OEt
(Eq. 331)
(67%)
MeC6H5, 110°, 5 h
O OEt
MeC6H5, 110°, 5 h
(76%)
(Eq. 332)
O
Reduction of Miscellaneous Nitrogen-Containing Compounds The combination of PhSiH3 with a catalytic amount of bis(tri-n-butyltin) oxide reduces azides to primary amines in excellent yields (Eq. 333).556 The reducing agent is (n-Bu)3 SnH formed in situ by the silane. Azides are converted into Boc-protected primary amines with the PMHS/Pd/C reagent (Eq. 334).557,558 N3
NH2
PhSiH3, [(n-Bu)3Sn]2O, n-PrOH, C6H6
(99%)
AIBN, reflux, 90-120 min OH N3
(Eq. 333)
OH
PMHS, 10% Pd/C
(90%)
(Boc)2O, EtOH, rt, 5 h
(Eq. 334)
NHBoc
The combination of Et3 SiH/Co2 (CO)8 reduces nitriles to the N ,N -bis(trimethylsilyl)amine (Eq. 335).559 These derivatives can be readily hydrolyzed to the primary amines. CN
TMS N TMS
TMSH, Co2(CO)8 CO, –20°
(64%)
(Eq. 335)
The organosilane reduction of hydrazones to hydrazines is readily accomplished in good yields with Et3 SiH/TFA (Eq. 336).560,561 N -Tosylimines294 are reduced to their N -Boc tosylamino counterparts,294 and are also reduced with (MeO)3 SiH/LiOMe in good yields.294 Benzyl-protected hydroxylamines are reduced with PhMe2 SiH/TFA.551 O Ph
N H
N
O
Et3SiH, TFA 0°, 4 h
Ph
N H
H N
(86%)
(Eq. 336)
104
ORGANIC REACTIONS
In an analogous fashion to the reductive deprotection of allyl alcohols and allyl esters, the deallylation of allylamines is also possible (Eq. 337).270 H N
NH2
PMHS, Pd(PPh3)4
(Eq. 337)
+
(90%)
THF, rt, 3-5 h
The tetrachloroferrate or tetrafluoroborate salts of alkylated alkyl- or arylnitriles (nitrilium ions) are reduced to imines with triethylsilane. Subsequent hydrolysis of the intermediate imines leads to aldehydes in good yields, thus providing an excellent overall route to aldehydes from nitriles (Eq. 338).28,562 +
NEt BF4−
CHO
1. Et3SiH, CH2Cl2, rt, 0.5-6 h
(90%)
2. H2O
(Eq. 338)
Aryldiazonium salts are reduced to the benzene derivatives in good yields (Eq. 339).563 N2
+
BF4−
Et3SiH, MeCN
(Eq. 339)
(72%)
rt, 16 h
O2 N
O2N
Reduction of Miscellaneous Sulfur-Containing Compounds Et3 SiH/TFA reduces disulfides to the corresponding mercaptans in modest yields (Eq. 340).564 Naphthyl thio ethers are reduced in rather poor yields to tetrahydronaphthalene with the combination Et3 SiH/BF3 •OH2 (Eq. 341).263 There is one report of the reduction of a diaryl sulfide to the hydrocarbon but the yield is low (Eq. 342).217 S
SH
Et3SiH, TFA S
SMe
Et3SiH, BF3•OH2
(Eq. 341)
(20%)
CH2Cl2, 0°, 24 h
SH
Et3SiH, BF3•OH2
S
(Eq. 340)
(45%)
60°, 25 h
(Eq. 342)
+
CH2Cl2, 0°, 22 h (25%)
(25%)
The reduction of 2,2 -dithiobis(1,3-dithiolanium) bis(tetrafluoroborate) to the thiocarbonate compound by triethylsilane takes place quantitatively (Eq. 343).565 S + S
S
(BF4)2 2
Et3SiH, MeCN, 90% ee.579 The complex 96 is highly successful in the diphenylsilane reduction of aryl alkyl ketones with high yields and >90% ee values.580,581 Dialkyl ketones are reduced with more mixed results, with 2-octanone showing 63% ee and ethyl 4-oxopentanoate 95% ee. The same system can be used to reduce 2-phenylcyclohexanone with no cis/trans selectivity, but excellent enantioselectivity (Eq. 347).390 + Ph2P (NBD)Rh
O
O —
OTf
S t-Bu
Ph
O
AgBF4, THF, 0°, 1 d
N Rh Cl3
Ph2P 95
Ph2SiH2, RhCl3, 96
O
N N
PPh2
94 O
O N
N
96 OH
OH Ph
+
Ph
(Eq. 347) (46%) 1S,2R 99% ee
(46%) 1S,2S 96% ee
A chiral oxazolinoferrocene ligand with iridium(I) is used for the diphenylsilane reduction of aryl alkyl ketones in nearly quantitative yields and >83% ee
ORGANOSILICON HYDRIDE REDUCTIONS
107
values.582 The dialkyl ketone, 2-octanone, is reduced with a poor 19% ee under these conditions. A catalyst prepared by the alkylation of [1,2-bis(tetrahydroindenyl)ethane]titanium(IV) 1,1 -binaphth-2,2 -diolate with methyllithium or n-butyllithium can be employed in the methyldiethoxysilane reduction of acetophenone with 99% ee.583,584 Other ketones do not show nearly the same ee values. Methylsilane is the actual proposed reducing agent in this system. The phosphinophenyloxazoline 97 is an effective ligand for the asymmetric rhodium(I) diphenylsilane reduction of aryl alkyl ketones, even with propiophenone, which has proven difficult with other systems, showing 91% ee and 91% yield (Eq. 348).585 A more general system involving mesitylphenylsilane and catalyst 98 permits the reduction of aryl alkyl ketones in very high chemical yields and >96% ee.586 The reduction of dialkyl ketones ranges from 72% ee for 2-octanone to 96% ee for the more stereo-differentiated adamantly methyl ketone.
Ph2P
O H Ph2P
N
N H 97
O
Fe
98
OH
Ph2SiH2, [Rh(cod)Cl]2
(Eq. 348)
97, MeC6H5, rt
Alkylated (R,R)-tetrahydroindenyltitanium difluoride and phenylsilane serve to asymmetrically reduce a variety of ketones, especially aryl alkyl ketones, in excellent chemical yields and >96% ee.587 The use of the easier to handle and less expensive PMHS is also highly effective in these transformations. In a related study using the (R,R)-tetrahydroindenyltitanium 1,1 -binaphth-2,2 -diolate precursor to the active catalyst, similarly impressive results are obtained.588 The in situ generation of CuH from organosilanes in the presence of either a BIPHEP (99) or a SEGPHOS (100) type ligand represents a general method for the asymmetric hydrosilylation of aryl alkyl ketones at low temperatures.
t-Bu OMe MeO MeO
P P
2
MeO MeO
Bu-t Bu-t
P P
2
OMe t-Bu
2
99
100
2
108
ORGANIC REACTIONS
These excellent catalyst systems show high reactivity, substrate-to-ligand ratios of >100,000 : 1, high chemical yields, the ability to employ the inexpensive PMHS as the hydride donor, and typical ee values in the >90% range.589,590 The most promising ligand found to date is DTBM-SEGPHOS (5,5 -bis[di(3,5-di-tertbutyl-4-methoxyphenyl)phosphino]-4,4 -bi-1,3-benzodioxole) 100 (Eq. 349). The BIPHEP ligand with copper(I) is also capable of asymmetrically reducing aryl alkyl ketones under similar conditions and with comparable results.589,591
OH
O Ph2MeSiH, CuCl, t-BuONa
(90%) 95% ee
100, MeC6H5, –78°
(Eq. 349)
Asymmetric Reduction of α,β-Unsaturated Ketones The enantioselective hydrosilylation of 2-pentylcyclopentenone is effected with PMHS and an active catalyst derived from (R,R)-ethylenebis(tetrahydroindenyl)titanium difluoride and phenylsilane (EBTHI)Ti (Eq. 350).587 The use of diphenylsilane, a rhodium catalyst, and (R,R)-(S,S)-BuTRAP as the chiral ligand gives similar results.576 Other related approaches give greatly inferior enantioselectivies.592 – 594 1. PhSiH3, (EBTHI)Ti, MeOH, 60°, pyrrolidine, MeOH, THF
O
OH
(Eq. 350)
2. PMHS, ketone, MeOH, 15°, 4 h (90%) 84% ee
The PMHS, copper-catalyzed reduction of β-substituted α,β-unsaturated ketones to saturated ketones is accomplished in good yield with ee values in the 90 to 95% range when (S)-p-Tol-BINAP is employed as the chiral ligand.595,596 Higher ee values are achievable with the use of a copper catalyst and (R)-100 as the chiral ligand (Eq. 351).597
O
O PMHS, CuH(PPh3), (R)-100 MeC6H5, –35°, 16 h Ph
(95%) 99.5% ee
(Eq. 351)
Ph
The sequence of chiral 1,4-reduction of a β-substituted cyclopentenone followed by electrophilic trapping of the intermediate enolate provides an efficient route to chiral 2,3-disubstituted cyclopentanones that generates two chiral centers in the process (Eq. 352).459
ORGANOSILICON HYDRIDE REDUCTIONS O
109
OSiPh2H
Ph2SiH2, CuCl, NaOBu-t (S)-p-TolBINAP, MeC6H5, 0°, 2-3 h
Ph
Ph 95% ee
(Eq. 352)
O BnBr, TBAT
Bn
CH2Cl2, MeC6H5, rt
(69%) dr = 94:6 Ph
Asymmetric Reduction of α,β-Unsaturated Esters and Lactones The chiral hydrosilylation of β-substituted α,β-unsaturated esters to their saturated counterparts is the subject of reports by two groups. The combination of triphenylphosphinecopper hydride and (R)-DTBM-SEGPHOS is reported to give excellent yields of the β-substituted esters (Eq. 353).598 Comparable yields, but with lower ee values, are reported for this transformation.599,600 O
O OEt
PMHS, CuH(PPh)3, (R)-100 H
t-BuOH, MeC6H5, 0°
OEt
(92%) 98% ee
(Eq. 353)
Ph
Ph
The copper-catalyzed chiral reduction of β-substituted α,β-unsaturated lactones with PMHS and (S)-p-Tol-BINAP in the presence of a hindered alcohol can be carried out in moderate to good yields with moderate ee values.599 The reaction is useful for both butenolides and pentenolides. Inferior results are realized with diphenylsilane as the reducing agent. Excellent results employing PMHS and the DTBM-SEGPHOS ligand are possible (Eq. 354).598 O
O PMHS, CuH(PPh3), 100
O Ph
O
t-BuOH, MeC6H5, 0°
(96%) 99% ee
(Eq. 354)
Ph
The asymmetric reductive rhodium- and iridium-catalyzed aldol reaction of α,β-unsaturated esters with aldehydes470,601,602 is proposed to involve a rhodium(I) or iridium(I) hydride as the active catalyst, which adds to the α,βunsaturated ester, followed by reaction of the intermediate rhodium or iridium enolate with an aldehyde.470 These transformations provide an excellent entry into α-alkyl-β-hydroxy esters in both high yields and high enantiomeric ratios. The reactions were first carried out with moderate success using the BINAP (2,2 bis(diphenylphosphino)-1,1 -binaphthyl) ligand to introduce the asymmetry.470,603 The use of various pybox ligands improves the yields of these transformations.604 The best results are obtained from the ligand indane-pybox (101) and an iridium catalyst,604 which was applied to an enantioselective synthesis of the macrocycle borrelidin (Eq. 355).601,602
110
ORGANIC REACTIONS O
Et2MeSiH, [(cod)IrCl]2
O + OMe
BnO
101, rt, 24 h
H
OH O BnO
OMe
(59%) syn:anti = 9.5:1 er syn = 98:2 O
N N
(Eq. 355)
O N
101
Asymmetric Reduction of α,β-Unsaturated Lactams The chiral reduction of β-substituted α,β-unsaturated lactams with PMHS in the presence of (S)-p-Tol-BINAP as the chiral ligand with a copper catalyst results in β-substituted lactams in excellent yield and with greater than 90% ee.599 This method has been applied in an efficient enantioselective synthesis of the antidepressant (−)-paroxetine (Eq. 356). O
O
PMPN
PMHS, CuCl2, NaOBu-t, t-AmOH
PMPN
(S)-p-Tol-BINAP, C6H5F, air, rt, 3 h F
(Eq. 356) (90%) 90% ee
F
(–)-paroxetine
Asymmetric Reduction of Imines Various chiral ligands with metal catalysts can be employed in the organosilane reduction of imines to amines. Many of these provide modest success. These include (oxazolino)diphenylphosphinoferrocene ligands with ruthenium,605 (−)DIOP/Rh(I),606,607 3,3 -BINOL (1,1 -bi-2-naphthol) and LiHMDS,608 and (S)phenyl N -formylprolinamide with trichlorosilane.609 Some excellent findings in the asymmetric organosilane reduction of both aryl alkyl and dialkyl imines have resulted in the development of practical, scaleable methodologies for this key transformation. The reduction of imines with the ethylenebis(η5 -tetrahydroindenyl)titanium (EBTHI)–TiF2 -derived catalyst 102 with either phenylsilane or PMHS as the reducing agent gives high chemical yields of the corresponding amine and ee values well in excess of 90% with most at 99% (Eq. 357).610 – 613 Straight-chain dialkyl imines are not as successful; for example, 2-(N -benzylimino)octane gives a 96% yield of (S)-(2benzylamino)octane with 69% ee.612 The CuH approach employed so successfully for the asymmetric organosilane reduction of ketones can be applied with equal success to the reduction of phosphoryl imines, thus providing a route to the asymmetric reduction of imines to primary amines via the hydrolysis of the resulting aminophosphorane.598,614
ORGANOSILICON HYDRIDE REDUCTIONS N
Cl
HN
PhSiH3, 102 OMe
111
OMe
i-BuNH2, 65°, 2.5 h Cl
E:Z = 15:1
Ti F
(92%) 99% ee
(Eq. 357)
F
102
COMPARISON WITH OTHER METHODS
Many different methods are known and used for the reduction of organic functional groups. These have been reviewed many times over the years and are too numerous to repeat here. The sequence of hydrosilylation of a multiple bond followed by removal of the silyl group is tantamount to the addition of hydrogen. Coupled with the keen current interest in asymmetric reductions, the use of hydrogen in asymmetric reductions and related reactions is highlighted here. The numerous asymmetric hydrogenations and asymmetric reductions with metal hydrides, including lithium aluminum hydride, sodium borohydride, and borane, coordinated or reacted with chiral diols, amino alcohols, diamines, and variations of these have been extensively reviewed.615 – 631 In view of the very large number of methods for the reduction of organic functional groups and the high interest in asymmetric reductions, the choice of competitive examples is limited to those that are representative of asymmetric hydrogenations. Asymmetric Hydrogenation of Olefins EBTHI–Ti, when treated with n-BuLi, catalyzes the hydrogenation of trisubstituted olefins in good yields and excellent enantioselectivity though undetermined configuration (ee = 83% to >99%) (Eq. 358)632 A zirconium version of this approach is also successful in the asymmetric hydrogenation of terminal olefins, although the enantioselectivities are not high.633 On the other hand, this system gives excellent ee values when applied to the hydrogenation of disubstituted cyclic olefins (Eq. 359)634 Ph
EBTHI–Ti, n-BuLi H2 (2000 psi)
Ph
Ph
Ph
(91%) 99% ee
(Eq. 358)
EBTHI–Zr, H2 (1000 psi) Ph
PhMe2NH(C6F5)4B
Ph
(Eq. 359)
(89%) 99% ee cis:trans = 98:2
Chiral phosphinodihydrooxazole iridium ligands are used to hydrogenate trisubstituted olefins in moderate yields and high enantioselectivity albeit of
112
ORGANIC REACTIONS
undetermined configuration.635 In a similar fashion and with equally impressive results, phosphine-oxazoline complexes of iridium 104, derived from [Ir(cod)Cl]2 and 103, are able to catalyze the hydrogenation of stilbenes (Eq. 360) and βmethyl cinnamic esters with both excellent conversion and enantioselectivity of undetermined configuration.636 The complex 105 also gives excellent results (Eq. 361).637
O R1
2P
N
R2 103 R1, R2 = alkyl, aryl + +
H O R1 2 P
N
O
BARF–
P t-Bu
R2
Ir
R
BARF–
105 R = i-Pr, t-Bu, i-Bu, Ph, Bn
104 R1 = c-C6H11, Ph R2 = t-Bu, adamantyl, 3,5-(t-Bu)2C6H3, CHPh2 Ph
N Ir
104 H2 (10-100 bar), rt-50°, CH2Cl2
Ph
Ph
Ph
(Eq. 360)
31% to >99% conversion 83-98% ee O Ph
105, H2 (50-100 bar) OMe
CH2Cl2
O Ph OMe >99% conversion 98-99% ee
(Eq. 361)
The asymmetric hydrogenation of trisubstituted olefins with iridium complexes of chiral phosphinite-oxazoline ligands of the general structure 106 also provides excellent results with ee values in the 85–99% range.638 The asymmetric hydrogenation of imines with these systems gives only moderate results. A similar fused phosphinite-oxazoline iridium catalyst, 107, gives good results with 1,1disubstituted and trisubstituted olefins with ee values of >97%, although ethyl β-methylcinnamate gives poor results.639 Asymmetric Hydrogenation of Ketones A number of asymmetric hydrogenations of prochiral ketones to highly enantiomerically enriched alcohols are available. A select few are highlighted here.
ORGANOSILICON HYDRIDE REDUCTIONS
113
R R N Ar1
O P(Ar2)2
Ir
O
106 R Bn Bn Me Bn Bn
1
+
Ar2 P Ir(cod) N Ph O
BARF–
107
Ar Ph Ph Ph 3,5-Me2C6H3 3,5-(t-Bu)2C6H3
Ar2
Ar = Ph, 2-MeC6H4
Ph 2-MeC6H4 Ph Ph Ph
The PennPhos ligands, for example 108, complexed with rhodium, provide an excellent system for the hydrogenation of aryl alkyl ketones with ee values in the range of 94–96% (Eq. 362). Phenyl isopropyl ketone shows only a 72% ee under similar conditions. Dialkyl ketones exhibit ee values in the range of 73–94% with this system (Eq. 363).640
P
P 108
O
[Rh(cod)Cl]2, 108, H2
OH
(Eq. 362)
2,6-lutidine, MeOH, 24 h, 20° (93%) 95% ee O
[Rh(cod)Cl]2, 108, H2
OH
(Eq. 363)
2,6-lutidine, MeOH, 24 h, rt (96%) 75% ee
Enantioselectivities in the range of 97.7–99.9%, with the majority in the range of 98.4–99.1%, are obtained in the asymmetric hydrogenation of aryl alkyl ketones with ruthenium catalyst 109.641 The same systems can hydrogenate β-keto esters (95.2–98.6% ee) and α,β-unsaturated acids (96.2% in a single example).642 Asymmetric transfer hydrogenation can be employed in the asymmetric hydrogenation of prochiral ketones with a ruthenium complex of bis(oxazolinylmethyl) amine ligand 110. Enantioselectivities are greater than 95%.643 The BINAP system of general structure 111 can be used in asymmetric hydrogenations; the compound in which Ar = 3,5-Me2 C6 H3 , R1 = R2 = 4-MeOC6 H4 ,
114
ORGANIC REACTIONS OMe N
Ar2 Cl H2 N P Ru N P Ar2 Cl H2
MeO MeO N
Ph Ph
OMe 109 Ar = Ph, 4-MeC6H5, 3,5-Me2C6H3
H N O
N N
O
Ph Ph 110
Ar2 Cl H2 N P Ru N P Ar2 Cl H2
R1 R3 R2
111 Ar 3,5-Me2C6H3 3,5-Me2C6H3 3,5-Me2C6H3
R1 R2 4-MeOC6H4 i-Pr —(CH2)4 — Ph Ph
PPh2
Fe
PR2
112 R3 4-MeOC6H H H
R c-C6H11 t-Bu 3,5-Me2-4-MeOC6H2 Ph 3,5-(CF3)2C6H3
and R3 = i-Pr effects the asymmetric hydrogenation of cyclopropyl methyl ketone (95% ee), cyclopropyl phenyl ketone (96% ee), and other aryl alkyl ketones (94 to 100% ee), and is also useful for the 1,2-reduction of enones (>90% ee).644 2,4-Pentanedione is hydrogenated to the 2-(R)-4-(R)-2,4-pentanediol in 97% ee with ligand 112 and [RuI2 (p-cymene)]2 . This system gives a wider range of enantioselectivity with prochiral ketones (22–97% ee) and α,β-unsaturated acids and esters (8–95% ee).645 o-BINAPO ligands of the type 113 complexed with ruthenium give good enantioselectivity in the hydrogenation of β-keto esters with the more hindered ortho-substituted aryl substituents giving the best results.646 The selectivities range from 87–99% ee. These same systems hydrogenate the double bond of β-amido acrylates in >90% ee. The TunaPhos ligands of general structure 114, when complexed with [RuPhCl2 ]2 , bring about the asymmetric hydrogenation of β-keto esters with
ORGANOSILICON HYDRIDE REDUCTIONS R
R H Me Ph 3,5-Me2C6H3 Ph
OPAr2 OPAr2 R
115
Ar Ph Ph Ph Ph 3,5-Me2C6H3
113
O (CH2)n O
PPh2 PPh2
114 n = 1-6
high ee values. The results compare very favorably with those obtained with (R)-BINAP and (R)-BIPHEP. The best results are found where n = 4, which gives a dihedral angle of the phosphines of 88 degrees.647 (R)-BINAP-RuBr2 can be successfully applied to the enantioselective hydrogenation of β-keto esters in the synthesis of (+)-(2R,3R)-corynomycolic acid 115. (S)-MeO-BIPHEP-RuBr2 was used in a similar manner in the synthesis of (R)-fluoxetine (116, Prozac) and (S)-duloxetine (117).648 CF3 OH O n-C15H31
OH C14H29-n
O
O NHMe•HCl
115
116
O
NHMe 117
The highly enantioselective reductive amination of α-keto acids as a route to amino acids is possible with ligand 118 [(3R,4R)-1-(N-benzyl)-3,4bis(diphenylphosphanyl)pyrrolidine, DEGUPHOS] and [Rh(cod)2 ]BF4 .649 (R,R)NORPHOS (2-exo-3-endo-bis(diphenylphosphino)bicyclo[2.2.1]heptene) and (2S,3S)-CHIRAPHOS (bis(diphenylphosphino)butane) are also good ligands for this transformation. Arylpyruvic acids give the best results (>95% ee). PPh2 BnN PPh2 118
The industrially important cis-(+)-methyl jasmonate 119 is conveniently prepared by the hydrogenation of enone 120 with Me-DuPHOS and [Ru(1,2 : 5,6-ηcod)(η3 -methallyl)2 .650
116
ORGANIC REACTIONS CO2Me
O
CO2Me
O 119
120
(S)-C3 -TunePhos (1,13-bis(diphenylphosphino)-7,8-dihydro-6H -dibenzo[f,h] [1,5]dioxonin) ruthenium catalyzes the hydrogenation of α-phthalimido ketones with enantioselectivities of >94%,651 leading to a highly enantioselective route to β-aminoethanols. Asymmetric Hydrogenation of Enol Acetates The diphosphine ligand 108 is useful in the asymmetric hydrogenation of enol acetates to chiral acetates, with 80.9% to >99% ee values being realized.652 The ruthenium TunaPhos complexes from ligand 114 catalyze the asymmetric hydrogenation of enol acetates with high enantiomeric excesses (Eq. 364).653 High yields and high ee values are obtained via hydrogenation of enol acetates with an achiral ruthenium catalyst and a lipase.654 This same system is used to convert prochiral ketones into chiral acetates with high enantiomeric excess. OAc OAc
Ru-(S)-C2-TunaPhos
(>99%) 95.9% ee
EtOH, H2 (3 atm), rt, 12 h
(Eq. 364)
Asymmetric Hydrogenation of α,β-Unsaturated Acids A study of various diphosphine ligands with rhodium catalyst systems for the hydrogenation of 2-methylenesuccinamic acid favors the DuPHOS (substituted 1,2-bis(phospholano)benzene) Rh(I) and Et-ferroTANE (1,1 -bis-2,4diethylphosphotano)ferrocene) Rh(I) systems, with the former being slightly better than the latter (Eq. 365).655 The conversions are high for both systems. BINAP-ruthenium complexes are successful in the asymmetric hydrogenation of α,β-unsaturated acids, with catalyst 121 showing the best results of those complexes studied.656 The chiral diaminoferrocenediphosphine ligand 122 catalyzes the reduction of trisubstituted acrylic acids with ee values of >92% (Eq. 366).657 O HO2C
O
[(R,R)-Me-DuPHOS Rh(cod)]BF4 NH2
H2, MeOH, rt
HO2C
NH2
(Eq. 365)
(98%) 94% ee
Itaconic acids are reduced in very high enantiomeric excesses (>97%) with Rh-TangPhos catalysts.658 Itaconic acid is reduced in 99.5% ee with the sugar-derived ferrocenyl phosphine 123.659
ORGANOSILICON HYDRIDE REDUCTIONS CO2H
CO2H
122 (NR2 = piperidyl)
Ph
Ph
H2, THF, MeOH
Ph2 P O O Ru P O O Ph2
117
Ph2P
(100%) 98.4% ee
N Me Fe
121
NR2
(Eq. 366)
PPh2 122 O
P O
O
Fe P
O 123
Asymmetric Hydrogenation of Acetamidoacrylates The understandably strong interest in the synthesis of highly enantiomerically enriched α- and β-amino acids has made the asymmetric hydrogenation of α- and β-acetamidoacrylates an active area of investigation. The catalyst Rh-TangPhos catalyze the reduction of β-aryl-α-acetamidoacrylates with high enantioselectivity (>99% and >97%, respectively).660 Chiral norbornadienyl diphosphoryl rhodium(I) complexes of the type 124 catalyze the asymmetric hydrogenation of α-acetamidoacrylates with high ee values (Eq. 367).661 Rhodium(I) trap complexes catalyze the hydrogenation of the α-acetamidoacrylates with ee values in the 80-88% range.662 Ph
CO2H
H2, 124, MeOH
Ph
NHCOMe
CO2H NHCOMe
(—) 98.4% ee
(Eq. 367) t-Bu
Rh +
BF4– Bu-t
124
The rhodium(I) complexes with hydroxyphospholane ligand 125663 or 126660 catalyze the asymmetric hydrogenation of α-acetamidoacrylates with ee values in excess of 98%. System 125 is also very effective in the asymmetric hydrogenation of β-acetamidoacrylates (up to 99.6% ee).664 The planar-chiral heterocyclic ligand 127 complexed with rhodium(I) catalyzes the hydrogenation of α-acetamidoacrylates in excellent yields and ee values from 79–96% under mild conditions.665 Other systems that prove successful in the highly enantioselective hydrogenation of α-acetamidoacrylates include the spirophosphinites 128 (94.2–97.2% ee)666 and the Josiphos ligands 129 with rhodium(I) (84–96% ee). Excellent
118
ORGANIC REACTIONS
Ph2P P
P
HO
P
P P
OH
Fe
t-Bu Bu-t OH
HO 125
126
127
results are also obtained with dimethyl itaconate and styrenes.667 The bis (phospholanes) of type 130, again with rhodium(I), catalyze the hydrogenation of α-acetamidoacrylates in 92.6–99.1% ee.668 The ligands 131,659 132,669 133,670 and 134670 all show good results in the asymmetric hydrogenation of αacetamidoacrylates, with 131 being especially effective, often rendering ee values of 0>99.9%.
Ph2PO
Cy2P
OPPh2
PPh2
RO
OR
P
P
Fe 128
P
RO
129
OR 130 R = Bn, t-Bu
O Fe
O
O Ph2P
O 131
O
O N P Me O
P N Me O 133
PPh2 132
O P NMe2 O 134
The various TunaPhos ligands with ruthenium(0) all catalyze the asymmetric hydrogenation of 2-acetylaminocyclopent-1-enecarboxylic acid ethyl ester in >99% ee.671 The larger ring sizes give lower ee values. Good results are obtained in the asymmetric hydrogenation of β-acetamidoacrylates with the Et-ferroTANE rhodium(I) complex.672 The Rh-TangPhos catalyst system brings about the hydrogenation of α-aryl-β-substituted enamides with high enantioselectivity.660 Asymmetric Hydrogenation of Enamides Enamides, in addition to the acrylates shown above, are also asymmetrically hydrogenated with many of the same systems that prove useful for the acetamidoacrylate reductions. The Rh(I)/BICP (2(R)-2 (i)-bis(dipenylphosphino)1(R),1 (R)-dicyclopentane) 132 and Rh(I)/DuPHOS systems work well (>90% ee) for the asymmetric hydrogenation of β-acetamidovinyl methoxymethyl ethers
ORGANOSILICON HYDRIDE REDUCTIONS
119
in an approach to enantiomerically enriched β-aminoethanols.673 The Rhbinaphane system 138 catalyzes the reduction of aryl alkyl enamides in up to 99.6% ee.674 Cyclic enamides are reduced in 37–99% enantiomeric excess with the Rh(I)/135 system (Eq. 368).675 NHAc
[Rh((S)-135)(NBD)]SbF6, H2
NHAc 98% ee
OMe MeO
Ph
MeO MeO
PPh2 PPh2
MeO
(Eq. 368)
Ph OMe 135
The Rh(I)/136 or Rh(I)/137 combination can be used in the asymmetric hydrogenation of 1-arylenamides in 90–99% ee, with Rh(I)/137 being the better of the two.676 Me-DuPHOS and related ligands with rhodium(I) reduce 1-aryl2-alkylenamides in >90% ee677 whereas the Rh(I)/DIOP combination carries this out in 97.3–99% ee selectivity.678 Finally, the Rh(I)/138 system reduces βsubstituted-α-arylenamides in 95–99% ee, and α-substituted acetamidoethylenes in 75.7–90% ee.674
NHPPh2 NHPPh2
136
NHPPh2 NHPPh2
137
P
P
138
Asymmetric Hydrogenation of Imines As an extension of the asymmetric hydrogenation of prochiral ketones to enantiomerically enriched alcohols, the reduction of imines has been a topic of interest in obtaining chiral amines of high enantiomeric purity. Several entries to enantiomerically enriched amines based on the approaches outlined above are available. These asymmetric hydrogenations have proved to be more difficult than those for prochiral ketones, but nevertheless show good promise. Iridium(III) hydride forms complexes with DIOP, BDPP (2,4-bis(diphenylphosphino)pentane), NORPHOS, and BINAP ligands to produce amines in 11– 80% ee.679 Similar modest results are obtained in the reduction of N arylketimines with an iridium(III) complex with (2S,3S)-CHIRAPHOS as the chiral ligand.680 The indium complexes with chiral phosphinodihydrooxazoles catalyze the enantioselective hydrogenation of imines in supercritical carbon dioxide with up to 80% ee, but generally lower ee values are observed in
120
ORGANIC REACTIONS
dichoromethane. The Rh(I)/chiral phosphine-catalyzed hydrogenation of imines is reported to give the chiral amines in up to 60% ee.681 This work presents a crystal structure of an intermediate rhodium(diphos)imine complex. The iridium(III) complex with the diphosphine ligand 138 gives amines in up to 99% ee and in excellent yields (Eq. 369).682 Cyclic imines undergo asymmetrical reduction via transfer hydrogenation using the catalyst EBTHI-Ti 102 (Eq. 370).683 NH2 N
138, H2 (1000 psi)
(77%) 99% ee
CH2Cl2, rt
MeO MeO
102, HCO2H N
(Eq. 369)
MeO MeO
NH
(95%) 95% ee
(Eq. 370)
The asymmetric hydrogenation of acyclic imines with the ansa-titanocene catalyst 102 gives the chiral amines in up to 92% ee.684,685 This same system applied to cyclic imines produces the chiral amines with >97% ee values.684,685 The mechanism of these reductions has been studied.686 EXPERIMENTAL CONDITIONS
Normal precautions to protect laboratory workers from exposure to chemical reagents should be followed. Strong acids such as trifluoroacetic acid and trifluoromethanesulfonic acid are often used in the preparations and should be handled with extreme care. The physical properties of organosilicon hydrides are similar to those of the analogous hydrocarbons, after taking account of the differences in molecular weights. They are generally lipophilic in nature. As previously mentioned, the chemical properties of organosilicon hydrides are considerably more benign than those of many metal-based reducing agents. However, organosilicon hydrides do react with strong bases and acids to produce hydrolysis products and hydrogen gas. This reaction occurs more rapidly with bases than with acids. Also, some of the lower molecular weight organosilicon hydrides, especially the parent compound SiH4 , are pyrophoric. A few of the organosilicon hydrides, such as trimethoxysilane and triethoxysilane, are toxic and have the ability to cause corneal damage. Many of the synthetically useful reactions of organosilicon hydrides are conducted in solution using solvents such as CH2 Cl2 , CHCl3 , CCl4 , MeCN, or THF. In general, it is important that anhydrous reaction conditions be used and that normal purification procedures be followed to ensure that the solvents used are pure and anhydrous. Finally, it must be mentioned that there are advantages in synthetic methods using polymeric organosilicon hydride reagents, such as PMHS, which are both relatively inexpensive and give high molecular weight products that are reasonably easy to separate from the desired organic products.
ORGANOSILICON HYDRIDE REDUCTIONS
121
EXPERIMENTAL PROCEDURES MOMO
OH
OH
C9H19-n
C10H21-n
Et3SiH
(68%)
TFA OMe
OMe
2-Decyl-5-methoxy-1-naphthol [Reduction of a Secondary Benzylic Alcohol to a Methylene Group with Concomitant Loss of a MOM Protecting Group].167 To a solution of 2-(1-hydroxydecyl)-5-methoxy-1-methoxymethyleneoxynaphthalene (0.525 g, 1.4 mmol) and Et3 SiH (1.628 g, 14 mmol) in CH2 Cl2 (8 mL) was added TFA (2.16 mL, 28 mmol) in CH2 Cl2 (3 mL) at room temperature and under an atmosphere of argon. The reaction mixture was stirred for 2 hours at room temperature, and then was poured into a saturated aqueous NaHCO3 solution (20 mL) and extracted with CH2 Cl2 (3 × 15 mL). The extract was washed with saturated aqueous NaHCO3 solution (15 mL), brine (15 mL), dried with MgSO4 , and evaporated. The crude product was purified by chromatography (SiO2 , benzene as eluent) to afford 2-decyl-5-methoxy-1-naphthol as needles: 0.319 g (68%); mp 61–62◦ (hexane); IR (CCl4 ) 3600, 1600, 1505, 1254, 1055, 880 cm−1 ; 1 H NMR (100 MHz, CDCl3 ) δ 7.60 (d, J = 9 Hz, 1H), 7.45 (dd, J = 2, 8 Hz, 1H), 7.15 (t, J = 8 Hz, 1H), 7.02 (d, J = 9 Hz, 1H), 6.56 (dd, J = 2, 8 Hz, 1H), 4.90 (br s, 1H), 3.94 (s, 3H), 2.68 (t, J = 7 Hz, 2H), 1.68 (m, 2H), 1.26 (m, 14H), 0.90 (t, J = 8 Hz, 3H). Cl Cl
Et3SiH, CH2Cl2 AlCl3, 0°
(74%)
Cyclohexane [Aluminum Chloride Catalyzed Reduction of a Dichloroalkane to a Hydrocarbon].189 After a solution of cis-1,2-dichlorocyclohexane (0.1582 g, 1.033 mmol) in CH2 Cl2 (3 mL) was cooled to 0◦ , Et3 SiH (0.299 g, 2.57 mmol) and AlCl3 (0.0345 g, 0.173 mmol) were added. The mixture was stirred for 30 minutes and then quenched with water (10 mL). Heptane (23.1 mg, 0.231 mmol) was added as an internal standard and the aqueous layer was separated and extracted with CH2 Cl2 . The combined organic layer was dried (MgSO4 ) and analyzed by GLC: 0.064 g (74%).
n-C11H23CO2Et
1. (EtO)3SiH, CsF, N2 30 min, 60° 2. aq. HCl, 30 min
n-C12H25OH
(90%)
1-Dodecanol [Fluoride-Promoted Reduction of an Ester to an Alcohol].83 A mixture of ethyl dodecanoate (2.18 g, 10.0 mmol) and triethoxysilane (3.77 g, 23.0 mmol) was added to CsF (1.52 g, 10.0 mmol) under nitrogen. The reaction was followed by IR spectroscopy. After 30 minutes at 60◦ , 12 N HCl (1 mL) in acetone (5 mL) was added. After 30 minutes, the mixture was extracted
122
ORGANIC REACTIONS
with ether (2 × 150 mL). The combined extracts were dried with MgSO4 and the solvents were removed. The residue was distilled under vacuum to give 1dodecanol: 1.8 g (90%); bp 145◦ /15 Torr. The GLC retention time was identical with that of an authentic sample. CHO
Et3SiH, TFA
O
(80%)
Dibenzyl Ether [Brønsted Acid Promoted Reduction of an Aldehyde to a Symmetrical Ether].311 To a stirred solution of benzaldehyde (5.4 g, 0.05 mol) and TFA (11.4 g, 0.1 mol) under argon was added dropwise, with cooling, Et3 SiH (8.1 g, 0.07 mol) at a rate such that the temperature of the reaction mixture did not exceed 40◦ . The solution turned a crimson color that gradually disappeared. Analysis by GLC showed the complete absence of the aldehyde immediately after addition of all of the silane. The products were separated by vacuum distillation at 20 Torr, collecting the fractions up to 125◦ . Dibenzyl ether was obtained from the residue by freezing out: 4 g (0.02 mol, 80%); mp 3–6◦ ; nD 25 1.5608. CHO +
EtOH
CH2OEt
1. Cl3 CCO2H, Et3SiH, 50-60°, 4 h
(90%)
2. H2O, NaHCO3
Ethyl Benzyl Ether [Brønsted Acid Promoted Reduction of an Aldehyde to an Unsymmetrical Ether].327 To a cooled mixture of benzaldehyde (4.3 g, 41 mmol) and absolute ethanol (3.7 g, 80 mmol) was added trichloroacetic acid (18.2 g, 111 mmol). Et3 SiH (6.96 g, 60 mmol) was then added dropwise with stirring while the mixture was maintained at 50–60◦ . After 4 hours, the reaction mixture was diluted with water, neutralized with aqueous NaHCO3 solution, and extracted with Et2 O. The dried ether extract was distilled and the 170–190◦ fraction was collected. Distillation from sodium gave ethyl benzyl ether: 4.8 g (90%); bp 187–189◦ .
n-C6H13CHO +
PhMe2SiH Ph
OTMS
EG acid
n-C7H15
O
Ph
(82%)
1-Heptyl 3-Phenylpropyl Ether [Electrogenerated Acid-Promoted Reduction of an Aldehyde to an Unsymmetrical Ether].333 A mixture of 1-heptanal (1.0 mmol), 3-phenylpropoxytrimethylsilane (1.2 mmol), tetra-nbutylammonium perchlorate (0.1 mmol), and lithium perchlorate (0.1 mmol) was dissolved in CH2 Cl2 (3 mL) in an undivided cell. The mixture was electrolyzed under constant current (1.67 mA cm−2 ) with platinum electrodes at ambient temperature. After 5 minutes, dimethylphenylsilane (1.2 mmol) was added dropwise and the electrolysis was continued (0.06 Faraday/mol). After completion of the reaction, one drop of Et3 N was added and the solution was concentrated. The residue was chromatographed on SiO2 to give 1-heptyl 3-phenylpropyl
ORGANOSILICON HYDRIDE REDUCTIONS
123
ether: 0.82 mmol (82%); bp 80–83◦ /1.0–2.0 Torr; IR (neat) 2955, 2925, 1605, 1110 cm−1 ; 1 H NMR (CDCl3 ) δ 7.22 (s, 5H), 3.37 (t, J = 6 Hz, 2H), 2.86–2.47 (m, 2H), 1.50–2.10 (m, 2H), 1.31 (br m, 10H), 0.87 (m, 3H). O
(n-Bu)3SiH, TFA, –35°
O (80%)
Dicyclohexyl Ether [Brønsted Acid Promoted Reduction of a Ketone to a Symmetrical Ether].313 Cyclohexanone (3.92 g, 40 mmol) and tri(n-butyl) silane (1.78 g, 20 mmol) were placed in a round-bottomed flask. TFA (75 mmol) was added slowly over a one-hour period to the reaction mixture, which was held at −35◦ . After complete addition, the reaction flask was placed in a freezer at −15◦ for 70 hours. Direct distillation gave dicyclohexyl ether: 2.91 g (16 mmol, 80%); bp 119–121◦ /18 Torr. CHO +
1. TrClO4, 0°, 5 min Ph
OTMS
2. Et3SiH, 5 min
BnO
Ph
(83%)
Benzyl 3-Phenylpropyl Ether [Trityl Perchlorate Catalyzed Reduction of an Aldehyde to an Unsymmetrical Ether].329 Under an argon atmosphere, a CH2 Cl2 (2 mL) solution of benzaldehyde (53 mg, 0.5 mmol) and 3phenylpropoxytrimethylsilane (0.5 mmol) was added to trityl perchlorate (9 mg, 0.026 mmol), and the solution was stirred for 5 minutes at 0◦ . A CH2 Cl2 (1 mL) solution of Et3 SiH (59 mg, 0.5 mmol) was added and stirring was continued for another 5 minutes. Then phosphate buffer was added, and the organic materials were extracted with Et2 O and dried over MgSO4 . After removal of the solvents under reduced pressure, isolation by TLC on SiO2 provided 94 mg (83%) of benzyl 3-phenylpropyl ether: IR (NaCl) 1100 cm−1 ; 1 H NMR (CDCl3 ) δ 7.10 (s, 5H), 7.00 (s, 5H), 4.30 (s, 2H), 3.30 (t, J = 6 Hz, 2H), 2.8-2.4 (m, 2H), 2.1-1.5 (m, 2H). 1. NaI, TMSCl, MeCN, rt CHO
2. TMDO
O
(84%)
Di-n-pentyl Ether [TMSI-Catalyzed Reduction of an Aldehyde to a Symmetrical Ether].314 A mixture of sodium iodide (0.15 g, 1 mmol), 1pentanal (1.06 mL, 10 mmol), and trimethylsilyl chloride (2.0 mL, 15.4 mmol) was stirred in MeCN (5.0 mL) at room temperature for 10 minutes, after which 1,1,3,3-tetramethyldisiloxane (TMDO, 1.79 mL, 10 mmol) was added. When the exothermic reaction had ended (30 minutes), a solution of 2.5 N HF in MeOH (30 mL) was added to the reaction mixture, which was then refluxed for 5 minutes. Work-up was carried out by diluting the solution with CH2 Cl2 (40 mL), washing with water (30 mL) and saturated aqueous NaHCO3 solution (20 mL), drying, and evaporating the solvents. Crude di-n-pentyl ether was purified by distillation: 0.65 g (84%); bp 185–189◦ /760 Torr.
124
ORGANIC REACTIONS O + EtOTMS
OEt
1. HMDS, I2, 0°, 10 min
(91%)
2. TMSH, 0° to 15°
Cyclohexyl Ethyl Ether [TMSI-Catalyzed Reduction of a Ketone to an Unsymmetrical Ether].334 In a 100-mL, three-necked flask equipped with a rubber septum, thermometer, magnetic stirring bar, and nitrogen inlet were placed finely powdered iodine (0.13 g, 0.50 mmol) and hexamethyldisilane (0.079 g, 0.54 mmol) in CH2 Cl2 (14 mL). The violet solution was stirred 10 minutes at room temperature, cooled to 0◦ , and a solution of cyclohexanone (1.04 g, 10 mmol) and ethoxytrimethylsilane (1.10 g, 10 mmol) in 10 mL of CH2 Cl2 was introduced via syringe. The reaction mixture was stirred for 10 minutes at 0◦ , after which TMSH was added directly from a gas cylinder by means of Tygon tubing attached to a hypodermic needle inserted through the rubber septum. The gas was allowed to slowly bubble through the solution until the color changed from violet to red-gold. During this time the internal temperature rose from 0◦ to 15◦ . The cold bath was removed and stirring was continued at room temperature for 2 hours. The mixture was washed with 10% aqueous Na2 S2 O3 solution (4 × 30 mL) and water (4 × 30 mL), and dried over MgSO4 . The volatiles were removed under reduced pressure on a steam bath to obtain pure cyclohexyl ethyl ether: 1.37 g (91%); bp 141–144◦ , 13 C NMR (CDCl3 ) δ 76.8, 63.0, 32.6, 26.4, 24.2, 15.9.
CHO
1. TMSCl, TMDO, SOCl2, 0° 2. ZnI2, reflux, 45 min
Cl
3. aq. HF, reflux, 10 min
(87%)
4-Methylbenzyl Chloride [Reductive Halogenation of an Aldehyde to a Benzyl Chloride].314 A mixture of 4-methylbenzaldehyde (1.18 g, 10 mmol), chlorotrimethylsilane (2.0 mL, 15.7 mmol), 1,1,3,3-tetramethyldisiloxane (TMDO, 1.79 mL, 10 mmol), and thionyl chloride (1.0 mL, 13.7 mmol) was cooled at 0◦ . Then ZnI2 (0.02 g) was added and a very exothermic reaction took place. When the spontaneous heating had ended, the mixture was heated at reflux with stirring for 45 minutes, and a 2.5 M solution of HF in MeOH (10 mL) was added. After being heated at reflux for 10 minutes, the solution was cooled to 0◦ , filtered, and taken up in CH2 Cl2 (30 mL)/water (40 mL). The aqueous layer was extracted with CH2 Cl2 (2 × 10 mL). The combined organic phases were dried (Na2 SO4 ) and the solvents were evaporated to afford crude 4-methylbenzyl chloride, which was purified by distillation: 1.22 g, 87%; bp 190–195◦ /760 Torr. O Ph
NHCO2Et
OH
PhSiMe2SiH, TFA 0°, 2.5 h
Ph
NHCO2Et (87%)
(1R,2S )-2-[(Ethoxycarbonyl)amino]-1-phenyl-1-propanol [Brønsted Acid Promoted Reduction of an α-Amino Ketone to an Erythro α-Hydroxy
ORGANOSILICON HYDRIDE REDUCTIONS
125
Amine].276 Dimethylphenylsilane (0.184 mL, 1.20 mmol) was added slowly to a TFA (1 mL) solution of (S)-2-[(ethoxycarbonyl)amino]-1-phenyl-1-propanone (221 mg, 1.00 mmol) at 0◦ , and the solution was stirred for 2.5 hours at 0◦ . Saturated aqueous NaHCO3 solution (20 mL) was added, and the resulting mixture was extracted with CH2 Cl2 (10 mL). The extract was dried over MgSO4 , filtered, and concentrated under reduced pressure to give the crude product, whose 1 H NMR spectrum showed exclusive formation (>99% selectivity) of (1R, 2S)2-[(ethoxycarbonyl)amino]-1-phenyl-1-propanol. Purification by preparative TLC (SiO2 , AcOEt/hexane, 1/1) afforded (1R, 2S)-2-[(ethoxycarbonyl)amino]-1phenyl-1-propanol (194 mg, 87%) as colorless crystals: mp 71◦ ; [α]20 D − 40◦ (c 0.245, CH2 Cl2 ); IR (KBr) 3350, 1694, 1552, 1273, 1043, 1028, 708 cm−1 ; 1 H NMR (CDCl3 ) δ 7.34 (s, 5H), 4.9 (br s, 1H), 4.84 (d, J = 3 Hz, 1H), 4.10 (q, J = 7.2 Hz, 2H), 4.2-3.8 (m, 1H), 2.83 (br s, 1H), 1.24 (t, J = 7 Hz, 3H), 0.99 (d, J = 7 Hz, 3H); MS (70 eV) m/z (relative intensity): M+ 223 (trace), 117 (18), 116 (66), 107 (11), 88 (21), 79 (15), 77 (14), 72 (11), 51 (5), 44 (100), 29 (23), 27 (7), 18 (5). Anal. Calcd for C12 H17 NO3 : C 64.55, H 7.67, N 6.27. Found: C 64.35, H 7.53, N 6.25. Ph
1. Et3SiH, NH4F, CH2Cl2, 0°, 0.5 h 2. rt, 3 h
Ph
(85%)
Phenylcyclopentane [Brønsted Acid Catalyzed Reduction of an Alkene to an Alkane].135 To a stirred solution of 1-phenylcyclopentene (1.44 g, 10 mmol), NH4 F (0.48 g, 13 mmol), and Et3 SiH (1.5 g, 13 mmol) was added TFA (5.1 g, 50 mmol) at 0◦ over a 10-minute period. The reaction mixture was then stirred for 20 minutes at 0◦ and at room temperature for 3 hours. The reaction mixture was quenched with ice water and extracted with CH2 Cl2 . The organic extract was washed with 10% aqueous saturated NaHCO3 solution, dried (CaCl2 ), and concentrated. Distillation provided phenylcyclopentane: 1.22 g (85%); bp 108–111◦ /20 Torr.
n-C15H31COCl
1. Et3SiH, (C6F5)3B, CH2Cl2, rt, 20 h 2. aq. HF, reflux, 7 h
n-C16H34 (96%)
n-Hexadecane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of an Acid Chloride to an Alkane].282 Et3 SiH (20 mmol) was added to a stirred solution of hexadecanoyl chloride (5 mmol) and tris(pentafluorophenyl)boron (5 mol%) in CH2 Cl2 . The reaction mixture was stirred for 20 hours at room temperature, quenched with Et3 N (0.25 g), filtered through Celite, and concentrated. The residue was mixed with 40% HF (5 mL) in EtOH (30 mL) and heated at reflux for 7 hours. Water (60 mL) was added, and the crude product was extracted with pentane (3 × 30 mL). The combined pentane solutions were washed with water and dried over MgSO4 . After the solvent and triethylfluorosilane were removed under vacuum, the product was purified by flash chromatography to give a 96% yield of n-hexadecane.
126
ORGANIC REACTIONS 1. Et3SiH, (C6F5)3B, CH2Cl2, rt, 20 h
n-C11H23CO2H
2. aq. HF, reflux, 7 h
n-C12H26 (91%)
n-Dodecane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of a Carboxylic Acid to an Alkane].282 Dodecanoic acid (5 mmol) in CH2 Cl2 was added to a CH2 Cl2 solution of tris(pentafluorophenyl)boron (5 mol%) and Et3 SiH (30 mmol). The reaction mixture was stirred for 20 hours at room temperature, quenched with Et3 N (0.25 g), filtered through Celite, and concentrated. The residue was mixed with 40% HF (5 mL) in EtOH (30 mL) and heated at reflux for 7 hours. Water (60 mL) was added and the crude product was extracted with pentane (3 × 30 mL). The combined pentane solutions were washed with water and dried over MgSO4 . After the solvent and triethylfluorosilane were removed under vacuum, the product was purified by flash chromatography to give a 91% yield of n-dodecane. CO2H
Et3SiH, (C6F5)3B, CH2Cl2 rt, 20 h
I
OSiEt3
(94%)
I
4-Iodobenzyloxytriethylsilane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of a Carboxylic Acid to a Benzyl Triethylsilyl Ether].282 Et3 SiH (16.5 mmol) was added to a stirred solution of 4-iodobenzoic acid (5 mmol) and tris(pentafluorophenyl)boron (5 mol%) in CH2 Cl2 . The reaction mixture was stirred for 20 hours at room temperature, quenched with Et3 N (0.25 g), filtered through Celite, and concentrated. The solvent was removed under vacuum and the product was purified by flash chromatography to give a 94% yield of 4iodobenzyloxytriethylsilane. 1 H NMR (CDCl3 , 500 MHz) δ 7.48 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 4.71 (s, 2H), 1.02, 0.68 (q, J = 8.0 Hz, 6H); 13 C NMR (CDCl3 , 126 MHz) δ 140.8, 131.7, 128.3, 121.07, 64.4, 7.2, 4.9; GC–MS m/z (% relative intensity, ion): 300 (1, M+ ), 271 (77, M–Et), 169 (100). PhMeSiH2, Cp2TiMe2 N
80°, 12 h
(50%) N SiHMePh
N -(Phenylmethylsilyl)-1,2,3,4-tetrahydropyridine [Reduction of a Pyridine].264 Phenylmethylsilane (3.5 mL, 25.6 mmol) and pyridine (1.0 mL, 12.5 mmol) were added to Cp2 TiMe2 (0.13 g, 0.7 mmol, 6 mol%). The solution color changed to dark blue, then purple, accompanied by gas evolution. The mixture was stirred for 12 hours at 80◦ . The 1 H-NMR spectrum showed that >95% of the pyridine had reacted to give a yield of ca. 80% of the crude product, which was distilled under vacuum to give 1.29 g (50%) of the title compound as a colorless liquid: bp 57◦ /0.12 Torr; 1 H NMR (300 MHz, C6 D6 ) δ 7.5 and 7.2 (2m, 5H), 5.01 (q, J = 3.3 Hz, 1H), 4.62 (m, 1H), 2.99 (m, 2H), 2.00 (m, 2H), 1.57 (m, 2H), 0.28 (d, J = 3.3 Hz, 3H); 29 Si NMR (59.9 MHz, C6 D6 ) δ −10.5;
ORGANOSILICON HYDRIDE REDUCTIONS
127
EIMS m/z (% relative intensity, ion): 203 (100, M+ ), 188 (18.5, M+ –CH3 ), 121 (76.6, M+ –C5 H8 N). PhSiH3, Mo(CO)6, NaHCO3
(81%)
THF, reflux, 1.5 h
Br O
O
Camphor [Reduction of an α-Bromo Ketone to a Ketone].197 A mixture of α-bromocamphor (2.24 g, 9.69 mmol), Mo(CO)6 (0.11 g, 0.53 mmol), phenylsilane (1.30 g, 12 mmol), and NaHCO3 (0.88 g, 10.5 mmol) in THF (6 mL) was heated at reflux for 1.5 hours. The mixture was cooled to room temperature, water (0.15 mL) was added, and the solvent was removed under reduced pressure. Distillation afforded camphor in 81% yield.
N n-C10H21
OTf N
Et3SiH, Pd(OAc)2, dppp DMF, 60°, 4 h
N n-C10H21 N (99%)
2-Phenyl-5-decylpyrimidine [Reduction of an Aryl Triflate to an Arene].201 To a mixture of 2-(4-trifluoromethanesulfonyloxyphenyl)-5-decylpyrimidine (1 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol), and dppp (8 mg, 0.02 mmol) in DMF (5 mL) at 60◦ was added Et3 SiH (0.4 mL, 2.5 mmol). At this time the solution changed color from light brown to deep brown. Stirring was continued for 4 hours, and the reaction mixture was cooled and diluted with Et2 O. The ether phase was washed with water, and with aqueous saturated solutions of NaHCO3 and NaCl. The ether layer was dried (Na2 SO4 ) and concentrated. The crude product was purified (99% yield) by chromatography: IR (KBr) 1549, 1435, 745, 691, 654 cm−1 ; 1 H NMR: δ 8.62 (s, 2H), 8.41 (m, 2H), 7.46 (m, 3H), 2.62 (t, J = 7.7 Hz, 2H), 1.8-1.4 (m, 2H), 1.27 (br s, 14H), 0.88 (t, J = 6.2 Hz, 3H).
(n-C16H33)2O
Et3SiH, (C6F5)3B CH2Cl2, rt, 20 h
n-C16H34 + n-C16H33OSiEt3 (98%)
(98%)
n-Hexadecane and 1-(Triethylsiloxy)hexadecane [Reduction of a Symmetrical Ether].145 Et3 SiH (1.1 mmol) was added to tris(pentafluorophenyl)boron (5 mol%) and bis-(n-hexadecyl) ether (1 mmol) in 1 mL of CH2 Cl2 . The reaction mixture was stirred for 20 hours at room temperature and then quenched with Et3 N (0.05 mL), filtered through Celite, and concentrated. GLC analysis with an internal standard showed the presence of n-hexadecane (98%) and 1(triethylsiloxy)hexadecane (98%).
128
ORGANIC REACTIONS CO2H
1. EtMe2SiH, 57, 1,4-dioxane, 20°, 0.5 h
OH
2. Add acid, stir 0.5 h
(CO)2Ru
(72%)
Ru(CO)2 Ru (CO)2 O 57
3-Phenyl-1-propanol [Reduction of a Carboxylic Acid to an Alcohol].280 To a solution of ruthenium catalyst 57 (616.5 mg, 25.2 µmol) in dioxane (0.45 mL) was added dimethylethylsilane (0.84 mL, 6.3 mmol). After the mixture had been stirred for 30 minutes at room temperature, hydrocinnamic acid (380 mg, 2.55 mmol) was added, and the stirring was continued for 30 minutes. Vigorous gas evolution occurred. The reaction was quenched with aqueous HCl, and the mixture was extracted with Et2 O. The organic phase was washed with aqueous saturated NaHCO3 and aqueous saturated NaCl solutions, and then dried with MgSO4 . The solvent was removed under vacuum and the product was purified by chromatography (EtOAc/hexane 1/9) to give 3-phenylpropyl alcohol: 248 mg, 72%.
t-BuO2C
N H
SBu-t H N
CO2Bu-t
Et3SiH, TFA, CH2Cl2 rt, 1.5 h
O
H2 N
SBu-t H N
CO2H + Me3CH
O (100%)
Cys(SBu-t)Gly [Reductive Deprotection of Boc and tert-Butyl Ester Groups in the Presence of a tert-Butyl Sulfide].307 Boc•Cys(SBu-t)Gly•OBu-t (1 mmol) was stirred with TFA (13 mmol), CH2 Cl2 (32 mmol), and Et3 SiH (2.5 mmol) at room temperature for 1.5 hours. After solvent removal, the residue was triturated with Et2 O and the precipitated product was removed by filtration, washed with Et2 O, and dried: 100%. N
OH
PMHS, (t-BuCO)2O, 10% Pd/C 40-50°, 7 h
H N
Boc (80%)
N -Boc-cyclododecylamine [Reductive Boc-protection of an Oxime].549 To a stirred solution of cyclododecanone oxime (1 mmol) in EtOH (10 mL) were added PMHS (180 mg, 3.0 mmol), di-tert-butyl dicarbonate (240 mg, 1.1 mmol), and 10% Pd/C (10 mg). The reaction mixture was stirred at 40–50◦ for 7 hours, after which time it was filtered and the filtrate concentrated under vacuum. The crude product was purified by column chromatography to give N -Boccyclododecylamine: 80%.
ORGANOSILICON HYDRIDE REDUCTIONS TBSO
129
TBSO Et3SiH, BF3•OEt2 N Ac
OMe
(97%)
CH2Cl2, –40°, 1-2 h
N Ac
(3R)-N -Acetyl-3-(tert-butyldimethylsiloxy)pyrrolidine [Reduction of an Aminal to an Amine].521 A solution of N -acetyl-2-methoxy-4-tert-butyldimethylsiloxy)pyrrolidine (2 mmol) and Et3 SiH (4 mmol) in dry CH2 Cl2 (3 mL) was treated with BF3 •OEt2 (4 mmol) at −40◦ . The reaction was monitored by TLC (1–2 hours). The mixture was diluted with CHCl3 and washed with aqueous saturated NaHCO3 and aqueous saturated NaCl solution. The organic layer was dried (MgSO4 ) and evaporated under reduced pressure. Purification of the residue by chromatography on SiO2 (hexane/EtOAc 10 : 1) gave the title compound as a colorless syrup: 97%; [α]24.5 D −23.4◦ (c 1.22, CHCl3 ); IR (film) 3350, 1650 cm−1 ; 1 H NMR (CDCl3 ) δ 4.58 − 4.25 (m, 1H), 3.80-3.10 (m, 4H), 2.10–1.60 (m, 2H), 1.98, 1.95 (2s, 3H), 0.80 (s, 9H), 0.01 (s, 6H); MS m/z: 228 (M+ –CH3 ); Anal. Calcd for C12 H25 NO2 Si: C 59.21; H 10.35; N 5.75; Si 11.54. Found: C 58.85; H 10.38; N 5.80; Si 11.18. O
PhMe2SiH, RhH(PPh3)4
OSiMe2Ph (87%) cis:trans = 92:8
CH2Cl2, 50°, 48 h
3,5-Dimethyl-l-cyclohexen-l-yl Dimethylphenylsilyl Ether [Reductive 1,4-Hydrosilylation of an Enone].374 3,5-Dimethyl-2-cyclohexen-1-one (0.124 g, 1.0 mmol) and RhH(PPh3 )4 (6 mg, 0.0052 mmol) were treated with PhMe2 SiH (0.177 g, 1.3 mmol) at 50◦ for 48 hours. After hexane (1 mL) was added, the reaction mixture was filtered and concentrated under vacuum. The crude product was purified by Kugelrohr distillation (90◦ / 1 Torr) to give a colorless liquid: 225 mg, 87%: IR 2952, 2918, 2913, 2902, 2870, 1666, 1428, 1369, 1253, 1197, 1182, 1121, 1079, 826, 787, 699 cm−1 ; 1 H NMR (200 MHz, CDCl3 ) δ 7.58 (m, 2H), 7.37 (m, 3H), 4.66 (s, 1H), (s, 1H), 2.21 (br s, 1H), 1.93 (m, 1H), 1.63 (m, 4H), 0.90 (d, J = 7.9 Hz, 3H), 0.86 (d, J = 7.0 Hz, 3H), 0.43 (s, 6H); 13 C NMR δ 149.7, 138.0, 133.4, 129.5, 127.7, 111.3, 40.8, 38.4, 30.9, 29.6, 22.6, 22.0, −0.9, −1.0; EIMS m/z: M+ calcd for C16 H24 OSi, 260.1596; found 260.1584. Anal. Calcd for C16 H24 OSi: C 73.80; H 9.30; found: C 73.78; H 9.25. O
O Ph2SiH2, ZnCl2, CHCl3
O
Pd(PPh3)4, rt, 1 h O
(95%)
O O
6,8-Dioxabicyclo[3.2.1]octan-4-one [1,2-Reduction of an Enone in the Presence of an Acetal].436 6,8-Dioxabicyclo[3.2.1]oct-2-ene-4-one (19 mg, 0.15 mmol) was dissolved in 3 mL of CHCl3 along with Ph2 SiH2 (55 mg,
130
ORGANIC REACTIONS
0.30 mmol) and ZnCl2 (20 mg, 0.15 mmol). Pd(PPh3 )4 (17 mg, 0.015 mmol) was added and the mixture was stirred at room temperature until the reaction was complete as determined by GLC. The reaction mixture was filtered through a short SiO2 column and purified by Kugelrohr distillation to give 18 mg (95%) of 6,8-dioxabicyclo[3.2.1]octan-4-one, having physical properties identical with literature values.
O
Et3SiH, H2SO4, H2O MeCN, 28°, 65 h
H N
Ac
(78%)
N -(exo-2-Norbornyl)acetamide [Reductive Amidation of a Ketone].313 To an acetonitrile (15 mL) solution of norcamphor (6.6 g, 60 mmol) and triethylsilane (7.7 g, 66 mmol) was added water (3.0 mL) followed by 9.0 mL of concentrated H2 SO4 (9.0 mL) at ice-bath temperature. The heterogeneous reaction mixture was stirred rapidly at room temperature for 65 hours. The mixture was then quenched by addition of 50% aqueous NaOH solution (30 mL) and the aqueous solution was extracted with CH2 Cl2 (3 × 50 mL). The combined extracts were passed through anhydrous MgSO4 and the CH2 Cl2 was removed under reduced pressure. The residue was washed three times with pentane to remove hexamethyldisiloxane and other soluble reaction products. The crude product was crystallized from Et2 O to give N -(exo-2-norbornyl)acetamide (6.5 g, 78%) whose 1 H-NMR spectrum and melting point were in accord with literature values.
O
Et3SiH, RhCl(PPh)3 50°, 2 h
O (88%)
Dihydro-β-Ionone [1,4-Reduction of an α,β-Unsaturated Ketone].435 A mixture of β-ionone (1.91 g, 10 mmol), Et3 SiH (1.27 g, 11 mmol), and RhCl(PPh3 )3 (9 mg, 0.01 mmol) was stirred at 50◦ for 2 hours under nitrogen. The NMR spectrum of the reaction mixture showed the exclusive formation of the 1,4-addition (silyl enol ether) product: 1 H NMR (CCl4 ) δ 5.23 (m, 1H), 4.28 (t, J = 7 Hz, 1H), 2.25-1.75 (m, 4H), 1.72 (br s, 3H), 1.63 (br s, 3H), 1.751.20 (m, 3H), 0.4–1.20 (m, 21H). The silyl enol ether was readily desilylated by treatment with K2 CO3 (10 mg)/MeOH (10 mL) with stirring for 1 hour at room temperature. After solvent removal, the crude product was distilled under reduced pressure to give dihydro-β-ionone: 1.70 g, 88.1% bp 88◦ /2.5 Torr. O
Ph2SiH2, RhCl(PPh3)3 rt, 30 min
OH
(89%)
β-Ionol [1,2-Reduction of an α,β-Unsaturated Ketone].435 A mixture of β-ionone (1.93 g, 10 mmol), Ph2 SiH2 (2.02 g, 11 mmol), and RhCl(PPh3 )3 (9 mg, 0.01 mmol) was stirred at room temperature under nitrogen. An
ORGANOSILICON HYDRIDE REDUCTIONS
131
exothermic reaction took place and the reaction was complete in 30 minutes. The NMR spectrum of the reaction mixture indicated the 1,2-reduction (silyl ether) product was formed exclusively: 1 H NMR (CCl4 ) δ 7.80-7.10 (m, 10H), 5.55-5.18 (m, 3H), 5.40 (s, 1H), 4.39 (m, 1H), 2.30-1.00 (m, 5H), 1.53 (m, 3H), 1.27 (d, J = 6 Hz, 3H), 1.0 (m, 5H), 0.86 (s, 3H), 0.77 (s, 3H). To the reaction mixture was added n-hexane (50 mL), and the precipitated catalyst was removed by filtration. Then MeOH (10 mL) and K2 CO3 (10 mg) were added to the filtrate. Methanolysis was complete within 1 hour at room temperature. The ratio of dihydro-β-ionone/β-ionol was 0 : 100 based on GLC and NMR analyses. After solvent evaporation, the residue was distilled to give β-ionol: 1.74 g, 89%; bp 99◦ /2 Torr. O 8
O
Ph2SiH2 NEt2
Ti(OPr-i)4, 20°
8
H
(90%)
Undec-10-enal [Reduction of an Amide to an Aldehyde].433 To a dry flask containing neat N ,N -diethylundec-10-enamide (0.155 mL, 0.65 mmol) under argon was added Ph2 SiH2 (0.135 mL, 0.72 mmol) and Ti(OPr-i)4 (0.196 mL, 0.65 mmol). Initial effervescence was observed [CAUTION!] and the reaction mixture was stirred at room temperature until TLC analysis showed complete consumption of the starting material (ca. 5 hours). The mixture was diluted with THF (20 mL), treated with 1 M HCl (10 mL), stirred for 1 hour, and poured onto Et2 O (80 mL). The organic layer was washed with 1 M HCl (3 × 10 mL), saturated aqueous NaHCO3 solution (2 × 10 mL), and saturated aqueous NaCl solution (10 mL), and then dried (MgSO4 ) and concentrated under vacuum. Flash column chromatography on SiO2 (hexane:Et2 O 15 : 85) afforded undecenal (99 mg, 90%). O
Me2ClSiH, TMSCH2CH=CH2 InCl3, CH2Cl2, rt, 2 h
Ph
Ph
(86%)
4-Phenylpent-1-ene [Reductive Allylation of an Aryl Ketone].427 Acetophenone (2.0 mmol) was added to a mixture of InCl3 (0.1 mmol), ClMe2 SiH (2.2 mmol), and allyltrimethylsilane (2.2 mmol) in CH2 Cl2 (10 mL) at room temperature. The reaction mixture was stirred for 2 hours, quenched with water (20 mL), and extracted with Et2 O (3 × 20 mL). After the organic layer was dried (MgSO4 ) and concentrated under vacuum, the residue was purified by chromatography (hexane) on SiO2 to give 4-phenylpent-1-ene (86%). O
PMHS, (C6F5)3B CH2Cl2, rt, 5-20 min
(88%)
6-Phenylhex-1-ene [Reduction of an Aliphatic Ketone Function to a Methylene Function].354 To a solution of 6-phenylhex-1-ene-4-one (1 mmol) in
132
ORGANIC REACTIONS
dry CH2 Cl2 (5 mL) and tris(pentafluorophenyl)boron (5 mol%) was slowly added PMHS (3 mmol) at room temperature. After 20 minutes, a vigorous effervescence was observed. The solvent was evaporated and the reaction mixture was dissolved in hexane and then filtered through a SiO2 pad using hexane. Evaporation of the volatiles afforded the 6-phenylhex-1-ene (88%) in pure form.
6
CO2Me
(EtO)3SiH, Ti(OPr-i)4
OH 6
50°, 16 h
(87%)
10-Undecen-1-ol [Reduction of an Ester to an Alcohol].291 Triethoxysilane (1.7 mL, 9 mmol) and methyl 10-undecenoate (594 mg, 3 mmol) were added to a test tube. Ti(OPr-i)4 (45 µL, 0.15 mmol) was added, and the test tube was fitted with a drying tube packed with Drierite to exclude excess moisture. The contents of the vessel were then stirred while being heated in an oil bath at 50◦ for 16 hours. The reaction mixture was washed into a 100-mL round-bottomed flask with THF (10 mL). Then 1 N NaOH (20 mL) was added slowly with stirring. NOTE: CAUTION: vigorous bubbling was observed. After 4 hours, the mixture was added to Et2 O (50 mL) and water (50 mL). After shaking, the layers were separated, and the aqueous layer was extracted with an additional 50 mL of Et2 O. The combined organic extracts were washed with 1 M HCl (2 × 50 mL), dried (MgSO4 ), filtered, and concentrated under vacuum to afford 10-undecen-1-ol as a clear oil: 443 mg, 87%. The product was >95% pure as determined by GLC and 1 H NMR analyses. Et3SiH, TFA
(CO)3Cr
(CO)3Cr
(92%)
CH2Cl2, rt, 1.5 h
HO
Tricarbonyl(1-endo-allyltetralin)chromium [Stereoselective Reduction of an Alcohol to a Hydrocarbon].182 A solution of tricarbonyl(1-exo-allyl-1endo-tetralol)chromium (150 mg, 0.46 mmol), Et3 SiH (0.22 mL, 1.4 mmol), and CH2 Cl2 (1 mL) was stirred at room temperature for 1.5 hours under nitrogen. The mixture was poured into water (10 mL) and extracted with Et2 O (2 × 10 mL). Evaporation of the organic layer under reduced pressure and purification by silica gel chromatography on SiO2 (1 : 8 Et2 O/petroleum ether) afforded tricarbonyl(1endo-allyltetralin)chromium as yellow crystals: 131 mg, 92%; mp 88–89◦ ; IR (CHCl3 )1960, 1880, 1635 cm−1 ; 1 H NMR (CDCl3 ) δ 6.15-4.80 (m, 7H), 2.952.10 (m, 5H), 2.05-1.35 (m, 4H). OMe Et3SiH, BF3•OH2 CH2Cl2, rt, 6 h
OMe (100%)
OMe
5-Methoxytetralin [Partial Reduction of a Substituted Naphthalene to a Tetralin].262 1,5-Dimethoxynaphthalene (300 mg, 1.0 mmol) dissolved in
ORGANOSILICON HYDRIDE REDUCTIONS
133
CH2 Cl2 (3–4 mL) was added dropwise to a flask containing BF3 •OH2 (1.1 g, 13 mmol) at 0◦ . After the addition was completed, the mixture was stirred for 10–15 minutes and allowed to warm to room temperature, and Et3 SiH (742 mg, 6.4 mmol) was added dropwise. The reaction mixture was stirred at room temperature for an additional 5–6 hours, neutralized with cold saturated aqueous Na2 CO3 solution, and extracted with CH2 Cl2 (3 × 15 mL). The combined organic extracts were washed with water (2 × 10 mL), dried (MgSO4 ), and evaporated to leave ca. 270 mg of brownish oil, which according to NMR and GC analyses contained ca. 90% of 5-methoxytetralin. Purification of the crude product was accomplished by column chromatography on SiO2 (CH2 Cl2 /Et2 O). OAc O OAc
OAc Ph2SiH2, ZnCl2, Pd(PPh3)4
O
THF, rt, 13 h, 50°, 2 h
AcO
(90%)
AcO
1,2,3-Trideoxy-D-ribo-hex-1-enopyranose Diacetate [Reduction of an Allyl Ester].196 To a THF (10 mL) solution containing tri-O-acetylglucal (349 mg, 1.28 mmol), diphenylsilane (489 mg, 403 mmol), and ZnCl2 (541 mg, 4.0 mmol) was added Pd(PPh3 )4 (70 mg, 0.06 mmol, 12 mol%). The solution was stirred at room temperature for 13 hours, then at 50◦ for 2 hours, and then mixed with Et2 O and washed several times with water. The ether layer was dried over Na2 SO4 and the solvent was evaporated. The yield of 1,2,3-trideoxy-D-ribo-hex1-enopyranose diacetate was 90% as determined by NMR using bibenzyl as an internal standard. The product was partially decomposed upon chromatographic purification over SiO2 , yielding 120 mg (53%). OH O
OH Et3SiH, TFA, LiClO4 (0.01 eq)
(86%)
rt, 4 h s-Bu
O
O
s-Bu
O
O
6-(2-Butyl)-4-hydroxy-3-ethyl-2-pyrone (Germicidin) [Reduction of a Ketone Carbonyl to a Methylene Group in a Multifunctional Compound].423 A TFA (15 mL) solution containing 3-acetyl-6-(2-butyl)-4-hydroxy-2-pyrone (2 mmol), Et3 SiH (1.29 mL, 8.0 mmol), and LiClO4 (2 mg, 0.02 mmol) was stirred at room temperature for about four hours while being monitored by TLC. The solvent was evaporated under vacuum and the residue was purified by column chromatography on silica gel (CHCl3 eluent) to yield racemic 6-(2butyl)-4-hydroxy-3-ethyl-2-pyrone: 337 mg, 86%; mp 95–97◦ (Et2 O/hexane); IR (KBr) 1160, 1285, 1430, 1595, 1680, 2885, 2945, 2980 cm−1 ; 1 H NMR (CDCl3 ) δ 6.22 (s, 1H), 2.48 (q, J = 7.4 Hz, 2H) and (m, 1H), 1.75-1.24 (m, 2H), 1.20 (d, J = 6.7 Hz, 3H), 1.11 (t, J = 7.5 Hz, 3H), 0.89 (t, J = 7.5 Hz, 3H); 13 C NMR (CDCl3 ) δ 69.6, 168.8, 168.0, 105.0, 100.9, 39.8, 27.5, 17.7, 16.4, 12.4, 11.6.
134
ORGANIC REACTIONS O
Cl HSiMe2Cl, In(OH)3
(99%)
CHCl3, rt, 2 h O2 N
O2N
1-(1-Chloroethyl)-4-nitrobenzene [Deoxygenative Chlorination of a Ketone].331 To a mixture of In(OH)3 (0.1 mmol) and p-nitroacetophenone (2.0 mmol) in CHCl3 (4.0 mL) was added ClSiMe2 H (2.4 mmol) under nitrogen. The reaction mixture was stirred for 2 hours at room temperature, and then was poured into EtOAc (50 mL) and washed with saturated aqueous NaHCO3 solution (50 mL). The organic layer was dried over MgSO4 and concentrated under vacuum to yield 99% of 1-(1-chloroethyl)-4-nitrobenzene. The physical and spectral data of the product were in excellent accord with known values. Et2MeSiH, PhNCO [Rh(cod){P(OPh)3}2]OTf
O
CH2Cl2, 45°, 13 h
OMe
O Ph
N H
O OMe (88%)
Methyl 2-(Phenylcarbamoyl)butanoate [Hydrocarbamoylation of an α,βUnsaturated Ester].475 To a solution of [Rh(cod){P(OPh)3 }2 ]OTf (9.9 mg, 0.01 mmol) in CH2 Cl2 (4 mL) was added a mixture of phenyl isocyanate (121 mg, 1.0 mmol), methyl crotonate (210 mg, 2.1 mmol), and Et2 MeSiH (205 mg, 2.0 mmol) in CH2 Cl2 (2 mL). The resulting mixture was heated at reflux for 13 hours under a nitrogen atmosphere. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography on SiO2 (4 : 1 hexane/EtOAc) to afford methyl 2-(phenylcarbamoyl)butanoate: 194 mg, 88%; mp 76.0–77.0◦ (hexane/EtOAc); IR (CCl4 ) 3371, 1722, 1689 cm−1 ; 1 H NMR (CDCl3 ) δ 8.74 (br s, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.30 (dd, J = 8.4 and 7.5 Hz, 2H), 7.10 (t, J = 7.5 Hz, 1H), 3.76 (s, 3H), 3.32 (t, J = 7.3 Hz, 1H), 2.03 (dq, J = 7.4 and 7.3 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H); 13 C NMR (CDCl3 ) δ 172.7, 166.3, 137.4, 128.8, 124.3, 119.9, 54.9, 52.5, 24.9, 11.8. Anal. Calcd for C12 H15 NO3 : C 65.14; H 6.83; N 6.33. Found: C 65.30; H 6.57; N 6.28. OMe Et3SiH, SnBr2, MeCOBr OMe
CH2Cl2, rt, 3 h
Br
(89%)
Benzyl Bromide [Reductive Bromination of an Acetal].506 To a suspension of tin(II) bromide (5.1 mg, 0.02 mmol) and benzaldehyde dimethyl acetal (54.8 mg, 0.36 mmol) in CH2 Cl2 (2.5 mL) were added successively Et3 SiH (65.0 mg, 0.56 mmol) and acetyl bromide (96.8 mg, 0.79 mmol) in CH2 Cl2 (1 mL) at room temperature under an argon atmosphere. The mixture was stirred for 3 hours at room temperature and quenched with a phosphate buffer (pH 7).
ORGANOSILICON HYDRIDE REDUCTIONS
135
The organic materials were extracted with CH2 Cl2 and the extract was dried over Na2 SO4 . Benzyl bromide (54.7 mg, 89%) was isolated by TLC on SiO2 . H N
Br
OEt O
BnO
Et3SiH, TFA –10°, 0.5 h
OCO2Et
H N
Br
OEt O
BnO
(94%)
OCO2Et
2-(Benzyloxy)-3-bromo-5-[(2-ethoxycarbonyl)ethyl]phenyl Ethyl Carbamate [Reduction of an Enamide to an Amide].535 A mixture of Et3 SiH (170 µL, 1.07 mmol) and (E)-2-(benzyloxy)-3-bromo-5-(2-ethoxycarbonyl) vinyl)phenyl ethyl carbamate (32 mg, 0.69 mmol) was cooled to −10◦ in an ice-salt bath under nitrogen, and treated with pre-cooled TFA (1.0 mL) in one portion. The two-phase mixture was rapidly stirred at −10◦ for 0.5 hour, poured into ice-cold saturated aqueous NaHCO3 solution, and worked up by extraction with CH2 Cl2 . The extracts were dried (Na2 SO4 ) and concentrated to give essentially pure title product: 30 mg, 94%; 1 H NMR (CDCl3 ) δ 7.5-7.3 (m, 5H), 7.29 (d, J = 2.0 Hz, 1H), 6.96 (d, J = 2.0 Hz, 1H), 4.99 (s, 2H), 4.74 (br t, J = 5.6 Hz, 1H), 4.21 (q, J = 7.2 Hz, 2H), 4.10 (q, J = 7.2 Hz, 2H), 3.38 (dt, J = 5.6 and 6.8 Hz, 2H), 2.74 (t, J = 6.8 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H), 1.22 (t, J = 7.2 Hz, 3H); 13 C NMR (CDCl3 ) δ 156.5, 152.9, 146.8, 145.1, 136.6, 136.4, 131.1, 128.4, 128.3, 128.2, 122.6, 118.1, 75.5, 65.2, 60.8, 41.7, 35.2, 14.6, 14.1; HRMS (CI) m/z: [M + H]+ calcd for C21 H25 BrNO6 , 466.0865; found, 466.0864.
N
NO2
PMHS, ZnCl2, Et2O rt, 12 h
N H
NO2 (75%)
3-Nitrobenzylamine [Reduction of an Imine to an Amine].539 To PMHS (300 mg) in a 25-mL flask fitted with a septum inlet and magnetic stirring bar was added freshly fused ZnCl2 (270 mg, 5 mmol) in dry Et2 O (5 mL) under a nitrogen atmosphere. After 10 minutes, N -phenyl-3-nitrophenylmethanimine (225 mg, 1 mmol) was added, and the reaction mixture was stirred at room temperature for 12 hours and extracted with 1 M HCl (2 × 15 mL). The aqueous layer was washed with CH2 Cl2 (15 mL) to remove non-amine impurities. The purified aqueous layer was made basic (pH ∼ 10) with 1 N NaOH and extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with water (15 mL) and brine (15 mL), and dried (Na2 SO4 ). The volatiles were removed and the residue was purified by column chromatography to yield 170 mg (75%) of the title product: 1 H NMR (CDCl3 ) δ 7.20 (d, J = 7.5 Hz, 2H), 7.70-6.50 (m, 7H), 3.50 (s, 2H); MS m/z: M+ 228, 136, 106, 91, 77.
136
ORGANIC REACTIONS I
1. TMSCl, NaI, MeCN, 5-10° O
(75%)
2. TMDO, reflux, 0.5 h
Cyclohexyl Iodide [Iodoreduction of an Oxirane to an Iodoalkane].357 A mixture of cyclohexene oxide (1.01 mL, 10 mmol), NaI (2.00 g, 13.3 mmol), and TMSCl (1.92 mL, 15 mmol) in anhydrous MeCN (10 mL) was stirred at 5–10◦ for 2–3 minutes. Then TMDO (1.79 mL, 10 mmol) was added and the mixture was heated at reflux for 0.5 hour. The remaining siloxane products were destroyed by adding 45% aqueous HF (2.0 mL) and heating at reflux for 5 minutes. The reaction mixture was taken up in CH2 Cl2 (30 mL), and the organic layer was washed with water (20 mL), 1 N NaHSO3 (10 mL), and water (20 mL) again. Drying (Na2 SO4 ) and evaporation of the solvents afforded crude cyclohexyl iodide, which was purified by Kugelrohr distillation to give pure product, 1.58 g (75%); bp 180–183◦ ; 1 H NMR (CCl4 ) δ 4.14 (m, 1H), 1.92 (m, 4H), 1.41 (m, 6H). O
O (PPh3)CuH, (R)-DTBM-SEGPHOS PMHS, MeC6H5, –35°, 6 h Ph
(95%) 99.5% ee Ph
(R)-3,3-Dimethyl-5-(2-phenylethyl)cyclohexanone [Asymmetric 1,4-Reduction of an Enone].597 To a 5-mL round-bottomed flask, flame-dried and purged with argon, was added CuHPPh3 (2.3 mg, 7.0 µmol) and (R)-DTBMSEGPHOS (1.9 mg, 1.6 µmol). Toluene (0.60 mL) was added and the solution was cooled to −35◦ . After PMHS (215 µL, 3.3 mmol) was introduced by syringe, 3-(2-phenylethyl)-5,5-dimethylcyclohexenone (192 mg, 0.84 mmol) was added. The mixture was stirred at −35◦ for 12 hours until the reaction was complete as determined by TLC (20% Et2 O/ligroin) and was then quenched by pouring into 3 N NaOH. Ether and water were added, and the mixture was stirred for 2 hours at room temperature. The aqueous layer was extracted with Et2 O (2 x), and the combined organic layers were washed with brine, dried over MgSO4 , filtered, and concentrated. The residue was purified by flash chromatography (10% Et2 O/ligroin) to afford the title ketone as a clear oil: 185 mg (95%), chiral GC (ketal from (R,R)-2,3-butanediol, Chiraldex B-DM 140) showed 99.5% ee. 1 H NMR (CDCl3 , 400 MHz) δ 7.31-7.17 (m, 5H), 2.64 (t, J = 8.2 Hz, 2H), 2.44 (ddd, J = 9.2, 2.0, 2.0 Hz, 1H), 2.21 (d, J = 13.2 Hz, 1H), 2.10 (ddd, J = 13.2, 2.2, 2.2 Hz, 1H), 1.35 (t, J = 12.4 Hz, 1H), 1.09 (s, 3H), 0.88 (s, 3H), 1.99-1.91 (m, 2H), 1.73-1.62 (m, 3H); 13 C NMR (CDCl3 , 125 MHz) δ 25.3, 32.3, 33.2, 34.6, 35.4, 39.3, 45.3, 47.6, 54.7, 126.0, 128.4, 128.6, 142.2, 212.0; HRMS calcd for C16 H22 O 230.1671; found 230.1663. TABULAR SURVEY
A thorough coverage of the literature through 2004 has been carried out based on the search of certain silanes. A small number of additional pertinent articles,
ORGANOSILICON HYDRIDE REDUCTIONS
137
particularly regarding the asymmetric silane reductions that were published later, are included. Tables are organized by the functional group classes undergoing change in the substrates. Table entries are ordered by increasing carbon count of the starting substrate. Protecting groups are included in the carbon count. Unspecified yields are denoted by (—). The following abbreviations are used in the tables: 10-C-6 18-C-6 Ac acac ACHN Ad AIBN An BARF BDE BINAP BINOL BIPHEMP BIPHEP bipy Bipymox Bmpp Bn Boc BOM BOX BPPFA BSA BTAF Bz Cbz cod coe cot Cp Cp* CSA DAST dba DBATO dbpp DBU
10-crown-6 18-crown-6 acetyl acetylacetone 1,1 -azobis(cyclohexylnitrile) adamantyl azobis(isobutyronitrile) anthracenyl tetrakis[3,5-bis(trifluoromethyl)phenyl]borate bond dissociation energy 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl 1,1 -bi-2-naphthol 2,2 -bis(diphenylphosphino)-6,6 -dimethyl-1,1 -biphenyl 2,2 -bis(diphenylphosphino)-1,1 -biphenyl bipyridyl 6,6 -bis(oxazolinyl)-2,2 -bipyridine benzylmethylphenylphosphine benzyl tert-butyloxycarbonyl benzyloxymethyl bis(oxazolino) 1 ,2-bis[diphenylphosphinoferrocenyl]ethyldimethylamine bis(trimethylsilyl)acetamide benzyltrimethylammonium fluoride benzoyl carbobenzyloxy 1,5-cyclooctadiene cyclooctene cyclooctatetraene cyclopentadienyl pentamethylcyclopentadienyl camphorsulfonic acid (diethylamino)sulfur trifluoride dibenzylidene acetone dibutylacetoxytin oxide di-(tert-butylphenyl)phosphite 1,8-diazabicyclo[5.4.0]undece-7-ene
138
DCE de dea dee DIBALH DIPOF DIOP diphos DME DMF DMI DMPU DMSO DMTS dpm dppb dppbz dppe dppf dppfc dppm dppp dr ds dma ebpe EBTHI ee EE EG EH er Fc Fmoc HAp HMDS H-MOP HMPA/HMPT KU-1 LAH Me-DuPHOS MEM
ORGANIC REACTIONS
1,2-dichloroethane diastereomeric excess diethanolamine diethoxyethane diisobutylaluminum hydride [2-(4,5-diphenyl-4,5-dihydro-1,3-oxazolin-2-yl)ferrocenyl]diphenylphosphine (2S,3S)-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane 1,2-bis(diphenylphosphino)ethane (see dppe) 1,2-dimethoxyethane N ,N -dimethylformamide 1,3-dimethyl-2-imidazolidinone 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H )-pyrimidinone dimethyl sulfoxide dimethylthexylsilyl 2,2,6,6-tetramethylheptane-3,5-dionate (“dipivaloylmethanato”) 1,4-bis(diphenylphosphino)butane 1,2-bis(diphenylphosphino)benzene 1,2-bis(diphenylphosphino)ethane bis(diphenyllphosphino)ferrocene diphenylphosphinoferrocene bis(diphenylphosphino)methane 1,3-bis(diphenylphosphino)propane diastereomeric ratio diastereoselectivity dimethylacetamide N ,N -ethylenebis(1-phenylethylamine) ethylenebis(η5 -tetrahydroindenyl)titanium enantiomeric excess ethoxyethyl electrogenerated 2-ethylhexanoate enantiomeric ratio ferrocene fluorenylmethoxycarbonyl hydroxyapatite hexamethyldisilazane 2-diphenylphosphino-1,1 -binaphthyl hexamethylphosphoric triamide phenol-formaldehyde sulfocationite lithium aluminum hydride 1,2-bis-(2,5-dimethylphospholano)benzene methoxyethoxymethyl
ORGANOSILICON HYDRIDE REDUCTIONS
MOM Ms mont MPM NBD Nf nmdpp NMP NORPHOS Np NR Ns o-dppb OTFA PE Piv PEHS PMB PMHS PNB PPA PPFA ppf PPHF PPTS PTC P(tm-tp)3 P(tp)3 p-Tol-BINAP PTSA pybox pymox rt SEGPHOS TADDOL TASF TBAF TBAT TBDPS TBS TEA TEAF TES
methoxymethyl methanesulfonyl montmorillonite methoxyphenylmethyl norbornadiene nonaflate (S)-neomenthyldiphenylphosphine N -methylpyrrolidone (−)-(R,R)-2-exo-3-endo-bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene naphthyl no reaction 4-nitrobenzenesulfonate 1,2-bis(diphenylphosphino)benzene trifluoroacetate phosphatidylethanolamine pivaloyl polyethylhydrogensiloxane p-methoxybenzyl polymethylhydrogensiloxane p-nitrobenzoate polyphosphoric acid [N ,N -dimethyl-1[2-(diphenylphosphino)ferrocenyl]ethylamine 2-[diphenylphosphinoferrocenyl]ethyldimethylamine pyridinium poly(hydrogen fluoride) pyridinium p-toluenesulfonate phase-transfer catalysis tris(2,2 ,6,6 -tetramethyl-m-terphenyl-5 -yl)phosphane tris(m-terphenyl-5 -yl)phosphane 2,2 -bis(p-tolylphosphino)-1,1 -binaphthyl p-toluenesulfonic acid pyridinebis(oxazoline) pyridinemono(oxazoline) room temperature (4,4 -bi-1,3-benzodioxole)-5,5 -diylbis(diarylphosphine) α,α,α ,α -tetraaryl-1,2-dioxolane-4,5-dimethanol tris(diethylamino)sulfonium difluorotrimethylsilicate tetra-n-butylammonium fluoride tetrabutylammonium triphenyldifluorosilicate tert-butyldiphenylsilyl tert-butyldimethylsilyl triethylamine tetraethylammonium fluoride triethylsilyl
139
140
Tf TFA TFAA TFPB THEATi(OPr-i) THF THP TIPS TMDO TMEDA TMS TMSBr TMSCl TMSI Tol Tr TRAP TRISPHOS Trityl Ts Vi
ORGANIC REACTIONS
trifluoromethanesulfonyl trifluoroacetic acid trifluoroacetic anhydride tetrakis-3,5-bis(trifluoromethylphenyl)borate [tris(hydroxyethyl)amino]titanium(IV)isopropoxide tetrahydrofuran tetrahydropyran triisopropylsilyl 1,1,3,3-tetramethyldisiloxane N ,N ,N ,N -tetramethylethylenediamine trimethylsilyl trimethylsilyl bromide trimethylsilyl chloride trimethylsilyl iodide tolyl triphenylmethyl 2,2 -bis[(dialkylphosphino)methyl]-1,1 -biferrocene 2,2 ,2 -tris(2,4,8,10)-tetra-tert-butyldibenzo[d,f ][1,3,2]dioxaphosphepin-6-yl-6-oxy)tri-2-propylamine triphenylmethyl p-toluenesulfonyl vinyl
141
R 2P
H
Fe
H
Fe
PPh2
Ph2P
Fe
H
Y Y
NMe2
H
Ar
6
Fe
PR2
SePh
Ar
PPh2
Fe
H NMe 2
19: C6F5
Y
30: Te
29: Se
28: S
18: 4-CF3C6H4
17: 3-CF3C6H4
16: Ph
H
2: n-Pr
1: Et
R
3
SPh
NMe2
PPh2
Ph2P
20
PPh2
NMe2
SPh
H
7
H
Fe
Fe
Fe
H
Fe
31
Fe
Fe
H
Ph2P
Fe
SeR
SPh
n-Pr
9:
OAc
Fe
H
Se
NMe2
Fe
14: 2,4,6-(i-Pr)3C6H2
13: Ph
12: c-C6H11
11: CH2Bu-t
10: n-Bu
allyl
8:
R
PPh2
PPh2
PPh2
21
H
NMe2
4
Fe
H
CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES
32
Se
PR2
H
Fe
Fe
SePh
TePh
R
NMe2
27: Ph
26: i-Pr
25: n-Bu
24: n-Pr
23: Et
22: Me
NMe2
PPh2
H
15
H
5
H PR 2
Fe
Fe
H
142
Fe
H
Se
Fe
NMe2
N
Ph
PPh2
N Ar
O
N
O
Ph
Ar
PR2
Fe
Ar = 3,5-(CF3)2C6H3 46
i-Pr
i-Pr
38
O
33
Se
H
Bn
1-naphthyl
39
44:
O
O
c-C6H11
R
Ph
Ph
Ph2P
43:
NMe2
N
O
47
PPh2
34
N
PPh2
i-Pr
Fe Cp*
N
O
R
45
P
Ph2P
N
O
Fe
N
48
H
N
O
PPh2
PPh2
O
CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued)
H
42:
41:
40:
R
Ph
t-Bu
i-Pr
Me
R
t-Bu
37:
i-Pr
R 36:
35:
143
N
MeS
67
N Pr-n
O
R
O
N
O
N PPh2
O
N
49
63
N
PPh2
N
Bn
58:
N R
O
Ph
R 57:
O
Ph2P
N
R
O
i-PrS
72: t-Bu
71: i-Bu
70: s-Bu
69: n-Bu
O
N
R
PPh2
Ph
68: i-Pr
R
50
N
O
64
N
N
N
O
N
i-Pr
N
R
O Ph
R
O
N
O
R
N
65
74: c-C6H11
73: Ph
R
N
CH2OTIPS
CH2OTBS
61:
Ph
60:
Et
O
N
53: SePh
52: SPh
59:
R
R 51: SMe
75
N
R
N
Bn
O
O
N
Y
62
N
N
N
Y
N
N
66
O
R
N
O
76
Et
O
56:
55:
54: S
S
O
Y
SMe
Bn
i-Pr
i-Pr
R
144
N
77
R
O
N
Ph
N
O
O
N
N
N
N
N R
78
N
O
Ph
Ph
93:
N
Et
92:
O
Me
R
Ph
91:
bornyl
N
bornyl
O
O
96
84
N
N
N
O
Ph
Ph
79
N
Ph
Ph
N
N
N
N
O
O
O
97
94
N
85
N
N N
N
N
80
O
Ph
O
O
N
Ph
Ph
N
O Ph
R
O
O
N
O
Pr-i
N
N
N
N
N
CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued)
98
N
95
N
N
N
R
O
R
O
N
N
O
90:
89:
88:
87:
86:
O
Pr-i
Ph
CH2OMe
Ph
s-Bu
t-Bu
i-Pr
Me
R
CH2OH
83:
Me
R 82:
81:
145
O
R
PAr2
MeO
Ar
O
O
P
P R
P
OMe
125
Ph
N P
OMe
Ph
122: 3,5-Me2-4-MeOC6H2
Np-2
N
R
R
O 104:
103:
O OR
O
O
R
Ph
Et
R
Ph2P
126
t-Bu
S
O
119: Et
118: Me
(NBD)Rh
OR
112: 2-naphthyl
111: 2,4,6-Me3C6H2
110: 4-MeC6H4
109: Ph
O
Rh Cl3
N
Np-2 Np-2 O
Ph
O
O
Ph
N
O 2-Np
Ph
Ph
Ph
R
O
121: 3,5-Me2C6H3
117: Et
116: Me
108: i-Pr
OR
OR
R
102: Me
107: Ph
R
101: i-Bu
100: s-Bu
99: i-Pr
PAr2
O
O
O
N
O
MeO
Ph
O
P O Ph
Ph
R
N
P O
Rh Cl3
N
Ph Ph
Ph
O
Ph
O
Ph
N
O
Ph
R
O
R
PAr2
PAr2
+
Ph
Ar
Ph
120
Ph
O
Ph
Np-2
2-Np
O
Rh
–
OTf
R
Ar
106: i-Pr
105: Ph
115: 2-naphthyl
114: 4-MeC6H4
113: Ph
Cl
O
124: 3,5-Me2-4-MeOC6H2
Ph
P
Ph
P Ar O
O
Np-2
R
N
P O
O
O
Ph
O
O
Ph
123: 3,5-Me2C6H3
Ph
Ph
Ph
2-Np
O
O
146
Ph
MeO HN
N H
Ph
Ph
153
OMe
HN
NH
147
NH
Ph
R
R
NHPh
148
BnNH
137: Ph
136: n-Bu
135: H
R
R
PhS 127
Ph2PO
Ph2PO
NHBn
NHR
NHR
R
HN
Ar
t-BuS
Ph2PO
NHBn
Ar
R
Ar
Ar 138: 2-MeOC6H4 139: Ph
159
N
N
150: 2,5-(MeO)2C6H3
149: 2-MeOC6H4
Ph
130
158: CH2naphthyl-1
157: c-C6H11
156: neo-C6H13
155: i-Bu
154: H
BnNH
Ar
Ph
NH
Ar
129: PMPS
128: PhS
R
Ph
NH
NHR
Ph
160
N
N
HN
R
151
NH
RNH
Ph
HN
CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued) R
Ph
Ph
146: Bn
152
NH HN
145: 2,4,6-Me3C6H2
144: 4-MeOC6H4
143: 3-MeOC6H4
142: CH2naphthyl-1
141: (CH2)2OMe
140: H
R
134: 1-naphthyl
133: c-C6H11
132: 4-ClC6H4
131: Ph
Ph
147
H 2N
170
Bn
PhN
O
O 177
P
NH2
OLi
161
O
NHPh
OH
OH
N H 171
OLi
O
Ph
Ar Ar
N N
OLi
Ph
172
O
178
H2N
LiO
H
MeN
NHAr
Ar
Ar
N
Ph
173
HO
N
186: O
O
185: 2,4,6-(MeO)3C6H2
184: 2,4,6-Me3C6H2
183: 2-naphthyl
182: 1-naphthyl
OLi
167: 3,5-Cl2C6H4
166: 3,5-(CF3)2C6H4
165: 3,5-Me2C6H4
164: 3,5-(MeO)2C6H4
163: 4-MeOC6H4
162: Ph
179
N
N Ph
N H
N
174
O
O
187
N
Ar
Ph
Ph
168
OH
H
n-BuN
Ph
N
NHMe
Me
N
Me
N
Ar
OH 175
Ph
H
MeN
O
Ar 181: 1-naphthyl
180: Ph
Ph
169
O
NMePh
NMe2
176
OH
148
i-Pr
i-Pr
O
O
191
O O
200
Ti
196
N
HN
SPh SPh
t-BuO
Ti
NH
HN
192
Cl
Cl
O
O
188
NH
i-Pr
Pr-i
SePh SePh
LiN
X
OBu-t
197
Ti
X
193
LiN
Ti
Ph
O
O
N
Cl
201
Cl
Ti
i-Pr Pr-i
X2 = 1,1'-binaphth-2,2'-diolate
N
NH
O O
N
Ph
(dimer)
Ph
189
N
Ph
Ti
F
Ph
N
202
H
198
Ti
Ti
Ph
F
H
NLi
194
Ti
HN
OPr-i
OPr-i
N
Cl
Me
P Ph2
+
Ti
PPh3
NO
195
NLi
Re
Si
199
Cl
Ti
203
Rh
N
Me
N
Ph
Ph2P
190
(dimer)
N
Ph
CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued)
PF6–
menthyl
Cl
Cl
R N
N
149 + R N X–
P tol2 c-C6H11 207
Cl
Ru
NO
BF4 Cl BF4
216: 2-Ad
X
N
N
PF6–
215: t-Bu
R
PPh3
Re
+
– + W(CO)2Cp B(C6F5)4
208
Ph
O
O
217
P
O
+
NO
O
O
209
N
N
PPh3
Re
205 (SReSC)
Ph2P
Rh
Ph2P
O
O
+ Cu –Cl
PF6–
i-Pr
i-Pr
PPh3
P
O
218
O
O
O
O
3
213: X = Cl
X–
212: X = BF4
N
N
PF6–
211: X = Cl
Pr-i
X–
Pr-i
NO
+
210: X = BF4
N
N
Ph
Re
206 (SReSC)
Ph2P
Rh
Ph2P
+
214: Me
204
tol2 P Cl N
Ph2P
Rh
Ph2P
+
150
Si
P
O
O
O
3
Si
(CO)2Ru
219
O
O
Me
225
Si 228
Me
O
Ru(CO)2
B
220
4
–
F
F
F
F
B
OH
OH
C6F5
C6F5
2
4
Ru(CO)2
221
Ru (CO)2 226
(CO)2 Ru
Na+
(CO)2Ru
CF3
CF3
Ph
Ph
230
Ph
Yb(hmpa)4
Si
Si
222
SiPh3
OH
OH
SiPh3
Me
Si
Si Me
O
Si
227
223
229
Me
O
F
F
F
F
Ru(CO)2 Ru (CO)2 O
Me
(CO)2Ru
CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued)
F
F
B C6F5
C6F5
F
F
4
(CO)2Ru
B C 6F 5
C 6F 5
224
3
Ru (CO)2
4
O
Ru(CO)2
151 I
E
O
NMe2
SiH2
Ph
O
O O – Si
H
A
NMe2
K+
O J
O
H O O – Si
CF3
CF3
F
– Si O
H
Li+
O
B
SiH2
SiH2
CF3
CF3
NMe2
Ph
Ph
CF3 CF3
Bu4N+
O
K
Si
O
CF3
CF3
G
CF3
CF3
CF3
O
– H Si
O
CF3
C
O O – Si H O O
O L
O
H O O – Si
Li+
K+
Li+
CF3
O
– H Si
O
CF3
CHART 2. ORGANOSILANE COMPOUND DESIGNATIONS USED IN TABLES
H
CF3
CF3
D
O
Li+
M
O
Li+
+ Ph3P=N=PPh3
H O O – Si
O O – Si H O O
152
C5
C4-6
2 2 2
OAc
O2CCF3
SC4H9-n 20 h
75 h
75 h
10 h
Time
(41) (40) (35) (39) (31)
20° 20° 20° 20° 20°
0.5 h 1h 1.5 h 4h 15 h
4 4 2.5 2.5 2.5
I (—)
0°
I 0.1 h
Time Temp
D
(15)
(0)
(13)
(80)
R
2.5
x
Et3SiH, TFA (x eq)
rt, 30 min
Et3SiH (1 eq), TFA (2 eq),
50°, 24 h
Et3SiD (1 eq), TFA (2 eq),
50°, 10 h
Et3SiH (1 eq), TFA (2 eq),
PhSiH3, 202
1
OBu-n
or
x
Et3SiH (x eq), TFA, 50°
Conditions
+
(10)
(6)
(2.8)
(10.8)
(6.3)
(—)
II
(—)
(90)
(—)
(—)
II
Product(s) and Yield(s) (%)
TABLE 1. ORGANOSILANE REDUCTION OF ALKENES
R
R
Alkene
233
232
221
203
687
234
Refs.
153
C6
C5-16
RN
1
O
(CH2)5CO2Et (CH2)5CO2Et (CH2)5CO2Et (CH2)5CO2Et Me
Ac
Ac
Ac
Ac
H Me
(CH2)5CO2Et
Ac
R2
H
R2
NR
1
R1
O
60 h 60 h 20 h 20 h
Ph3SiH Ph2SiD2 Ph3GeD Et3SiH
50°, 10 h
Et3SiH (1 eq), TFA (2 eq),
CD2Cl2, –75°, 5 min
Et3SiH, TMSOTf,
KU-1, 55°, 5 h
Et3SiH (1.1-1.2 eq), HCO2H,
HOAc, KU-1, 55°, 5 h
Et3SiH (1.1-1.2 eq), HCO2H,
CH2Cl2, 20°, 30 min
Et3SiH (1.2 eq), 65% HClO4,
20 h
60 h
Et3SiH or Et3SiD
Et3SiH
20 h
1
rt
I
I (92)
I (42)
(83)
(—)
(98)a
(78) 92
50
98
96
(65)
rt 50°
95
(30) 94
50
(70)
%I
(70)
I + II
1
RN (D)H
(27)
R2
NR + H(D)
1
rt
I
O
(92)
(23)
rt
rt
50°
O
RN (D)H
Time Temp
Et3SiH or Et3SiD
R3SiH
50°, 20 h
R3SiH (1 eq), TFA,
HCl, CH2Cl2, rt
Et3SiH (2 eq), AlCl3 (1.0 eq),
II
O
R2
NR1 H(D)
203
216
208
208
214
688
136
154
C6
Alkene
400 h 3h 6h 24 h 24 h
20° 50° 50° 50° 80°
20° 20°
3h 50 h
2 2
–10°, 0.5 h
Et3SiD (1 eq), TFA (2 eq),
(52)
–10°
0.5 h
3
D
(40)
(59)
–10°
0.5 h
I (78)
Temp
Time
I
(20)
2
D
I (93)a
(80)
(87)
(67)
(48)
(75)
I
x
Et3SiH, TFA (x eq)
rt, 72 h
Et3SiH (1 eq), TFA (2 eq),
CD2Cl2, –75°, 5 min
Et3SiH, TMSOTf,
50°, 24 h
Et3SiD (1 eq), TFA (2 eq),
CD2Cl2, –75°, 5 min
Et3SiH, TMSOTf,
Time
Temp
Et3SiH (1 eq), TFA (2 eq)
Conditions
+
+
II
(80)
(—)
(2)
(0.5)
(0)
II
I
(96)a
(90)
I + II (80)
+ II
Product(s) and Yield(s) (%)
TABLE 1. ORGANOSILANE REDUCTION OF ALKENES (Continued)
221
233
232
216
221
216
222
Refs.
155
O
O 3.5 h 1h 3h
3 4 5
HCl, CH2Cl2, rt, 3 h
Et3SiH (5 eq), AlCl3 (2.5 eq),
HCl, 20°, 1 h
Et3SiH (3 eq), AlCl3 (2 eq),
Time
x
HCl, CH2Cl2, rt
Et3SiH (x eq), AlCl3 (3 eq),
20°, 24 h
Et3SiH (10.2 eq), TFA (13.2 eq),
PhSiH3, 202
PMHS, Pd/C, EtOH, 80°
PTSA (1 eq), 40°, 2 h
EtCl2SiH (2 eq), AlCl3 (1 eq),
PTSA (1 eq), 40°, 2 h
EtCl2SiH (2 eq), AlBr3 (1 eq),
50°, 50 h
Et3SiD (1 eq), TFA (2 eq),
50°, 10 h
Et3SiH (1 eq), TFA (2 eq),
20°, 90 h
Et3SiH (2 eq), TFA (4 eq),
I
I (35)
I (40)
(41)
(40)
(23)
O
I (—)
I (100)
I (17)
I
O
D
O
CF3
(23)
(60)
(—)
(65)
(65)
136
146
136
230
687
316
192
192
221
203
233
156
C7
Alkene
50° 50° 20° 50° 20°
2 2 2.5 10 120 h
10 h
120 h
10 h
10 h
Time
AlCl3 (0.2 eq), CH2Cl2, rt
Et3SiH (1.4 eq), HCl (xs),
CH2Cl2, 20°, 30 min
Et3SiH (1.2 eq), 65% HClO4,
TFA (8 eq), O2NC6H5, 50°, 3 h
Et3SiO(EtHSiO)nSiEt3 (0.1 eq),
O2NC6H5, 50°, 3 h
Et3SiH (1 eq), TFA (8 eq),
Temp
x 1.5
Et3SiH (1 eq), TFA (x eq)
50°, 24 h
Et3SiD (1 eq), TFA (2 eq),
50°, 10 h
Et3SiH (1 eq), TFA (2 eq),
Et3SiH (0.87 eq), TFA, rt, 120 h
KU-1, 55°, 5 h
Et3SiH (1.1-1.2 eq), HCO2H,
Conditions
I
(78)
(72)
(73)
(67)
(40)
I (100)
I (97)
I (94)
I (92)
I
I (—)
D
(80)
(78)
(100)
Product(s) and Yield(s) (%)
TABLE 1. ORGANOSILANE REDUCTION OF ALKENES (Continued)
213
214
207
207
203
221
203
202
208
Refs.
157
1.5 h 2h 2h 2h 3.5 h 2.5 h 2.5 h 2h 2h
EtOH n-BuOH n-C8H17OH n-C12H25OH n-C12H25OH (n-Bu)2O (n-C8H17)2O (n-C8H17)2O n-C4H9OC12H25-n
(68) (93)
60° 60°
(50) (25) (5) (0) (0) (35)
CF3CO2H ClF2CCO2H Cl3CCO2H Cl2HCCO2H CH3CO2H 4-MeC6H4SO3H
Acid
acid, 130°, 10 h
Ph2SiH2 (1 eq), O2NC6H5,
(0)
(—)
rt
(5)
(—)
rt
CH2Cl2
(—)
60°
(37)
(73)
60°
MeOH
(65)
rt
(77)
(72)
rt
HOAc
(100)
60°
(96)
96% H2SO4
Temp
HCO2H
I
I
I
HCO2H, HOAc
Solvent
KU-1, 55°, 5 h
Et3SiH (1.1-1.2 eq), HCO2H,
Time
Solvent
Ph2SiH2 (1.2 eq), H2SO4 (30 eq)
(89)
(70)
(69)
(61)
(65)
(—)
(63)
(62)
(—)
90% H2SO4
134
208
209
158
C8
C7
or
Alkene
CHCl3 4-O2NC6H5
3 5 5h
5h
Time
PMHS, Pd/C, EtOH, 80°
20°, 24 h
Et3SiH (10.2 eq), TFA (20.3 eq),
PhSiH3, 202
BF3•OEt2 (0.4 eq), 20°, 24 h
Et3SiH (5 eq), TFA (10 eq),
20°, 24 h
Et3SiH (5 eq), TFA (10 eq),
PhSiH3, 202
PTSA (1 eq), 40°, 2 h
EtCl2SiH (2 eq), AlCl3 (1 eq),
Solvent
x
TFA (x eq), solvent, 20°
(0.1 mol%),
Et3SiO(EtHSiO)nSiEt3
(0.25 mol%), TFA, 50°, 20 h
Et3SiO(EtHSiO)nSiEt3
Ph2SiH2, O2NC6H5, 130°
Conditions
I
(89)
(52)
I
I (—)
I (22)
I (—)
I (65)
I
I (100)
CF3CO2
+
+
O2CCF3
(88)
II III I + II + III (—), I:II:III = 62:20:17
+
O2CCF3
(3.5)
(98)
Product(s) and Yield(s) (%)
TABLE 1. ORGANOSILANE REDUCTION OF ALKENES (Continued)
O2CCF3
(—)
316
230
687
230
230
687
192
207
207
193
Refs.
159
C8-9
O
R
Cl
I (95)
(47)
Me
R
II
(85)
H R
D
Cl
(—)
(45)
BF3•OEt2 (1 eq), 20°, 24 h
O
O
I
+
(20) +
Et3SiH (6.5 eq), TFA (12.1 eq),
CF3CO2D (2.5 eq), 60°, 7 h
Et3SiH (1.5 eq),
TFA (x eq), 3 h
Et3SiH (1.5 eq),
C6H6, rt, 6 h
PMHS-Pd nanocomposite,
C6H6, rt, 4 h
I (—)
PhSiH3, 202
I
PMHS-Pd nanocomposite,
50°, 10 h
Et3SiH (1 eq), TFA (2 eq),
20°, 24 h
Et3SiH (5.1 eq), TFA (13.1 eq),
Et3SiH (1 eq), TFA (2 eq), 20°
20°, 24 h
Et3SiH (5.1 eq), TFA (13.1 eq),
x
(66)
60° 5
(80)
(85)
(48)
(54) 60°
70°
Temp
1.5
(74)
3.5
2.5
1.5
(72)
1.3
(58)
24 h 240 h
1.5
(13)
2h 144 h
I:II
I + II
Time
O2CCF3
230
251
251
219
219
687
203
230
229
230
160
C9
C8-18
1d 1.5 d 1d 1.5 d 1d
n-C10H21
n-C12H25
n-C14H29
n-C16H33
60°, 10 h
Et3SiH (1 eq), TFA (8 eq),
C6H6, rt, 3 h
PMHS-Pd nanocomposite,
BF3•OEt2 (1 eq), 20°, 24 h
Et3SiH (6.5 eq), TFA (12.1 eq),
Et3SiH (2 eq), TFA (3 eq)
I
(55)
MeO
(73)
I (25) + II (—)
I
I (75)
BF3•OEt2 (1 eq), 20°, 24 h
Et3SiH (6.5 eq), TFA (12.1 eq),
(96)
(97)
(73)
(97)
(90)
(100)
I (70)
R
Et3SiH (2 eq), TFA (3 eq)
Et3SiH, TFA
PMHS, Pd/C, EtOH, 80°
1d
Time
n-C8H17
EtOH
Et3SiH (2 eq), PdCl2 (10 mol%),
Conditions
+
(95)
II
(—)
(25)
(15)
Product(s) and Yield(s) (%)
TABLE 1. ORGANOSILANE REDUCTION OF ALKENES (Continued)
n-C6H13
R
MeO
R
Alkene
689
219
230
231
230
231
233
316
220
Refs.
161
C10
O
O
H
D
I
37 40 42 35 54 58 72 77 83 93
0.36 0.60 1.1 1.1 1.1 1.1 1.1 0.55 1.1 1.1
n-BuH2Si Et2HSi Et3Si (i-C5H11)3Si (c-C5H9)3Si Ph3Si (s-Bu)3Si (t-Bu)2HSi (t-Bu)2MeSi (t-Bu)3Si
R3Si
rel % I
H
O
x
rt, 95)
Product(s) and Yield(s) (%)
TABLE 4. ORGANOSILANE REDUCTION OF HALOCARBONS
197
195
186
146
185
195
59
195
199
Refs.
193
C6
C5-11
C5
R
Br
O
Br
Cl
Br
Cl
Cl
Br
Br
Cl
Br
Cl
Cl
Cl
Cl
Cl
Br
I (~55%)
I
Et3SiH (5 eq), AlCl3 (0.1 eq)
I
I (57)
R
I (85)
I (72)
I (72)
I (70)
I
I (100)
Et3SiH (0.89 eq), AlCl3, rt, 15 h
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
diglyme, 75°, 1.2 h
PPh3 (16 mol%), NaHCO3 (80 mol%),
PhSiH3 (160 mol%), Mo(CO)6 (4 mol%),
+
+ R
(72)
II
(67)
I (72) (68) (58)
n-C4H9 n-C8H17
(64) n-Pr
Et
R
(8)
II
(—)
(7)
(7)
(5)
146
185
189
189
189
189
189
189
189
197
194
C6
Br
Br
Cl
Cl
Br
Cl
Cl
Br
Halocarbon
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
C5H12, 40°, 95)
I
O
O
O
O
I (88)
I (74)
(0)
20 h
0.75
3
(>95)
(80)
OEt
(37)
1.5 h
1.5
3
(75)
(75)
(75)
0.5 h
(>95)
(92)
0.5 h
2
2
Time
2
y
3
x
195
195
197
197
197
195
136
189
189
196
C7
C6-12
R
X
Br
Br
Cl
Br
Cl
Br
Cl
Halocarbon
R3 = Et3, EtMe2, Ph2Et, (C6H11)2Et
AlCl3 (25 mol%),
R3SiH (1.3 eq), CH2Cl2,
20°, 30 min
Et3SiH (6 eq), AlCl3 (0.55 eq),
20°, 30 min
Et3SiH (6 eq), AlCl3 (0.55 eq),
20°, 30 min
Et3SiH (2.5 eq), AlCl3 (0.25 eq),
C5H12, 40°, 95)
Time
2-I 4-I
10 min 25 min
2-Br 2 min
X
Product(s) and Yield(s) (%)
TABLE 4. ORGANOSILANE REDUCTION OF HALOCARBONS (Continued)
Ar
ArOTf
RX
X
Halocarbon
188
201
288
195
Refs.
201
O
O
Cl
Br
Cl
DMSO, Bn3N (1.4 eq), 110 °, 3 h
PMHS, (Ph3P)4Pd (5 mol%), MeCN,
NaHCO3 (110 mol%), C6H6, 80°, 3.25 h
Mo(CO)6 (6 mol%), PPh3 (27 mol%),
PhSiH3 (120 mol%),
PPh3 (0.16 eq), THF, rt, 24 h
Ph2SiH2 (1.4 eq), Pd(OAc)2 (8 mol%),
THF, rt, 0.1 h
PhSiH3 (1.5 eq), (Ph3P)4Pd (8 mol%),
THF, rt, 20 h
Et3SiH (1.5 eq), (Ph3P)4Pd (8 mol%),
THF, rt, 0.5 h
Ph2SiH2 (1.5 eq), (Ph3P)4Pd (8 mol%),
(Ph3P)4Pd (7 mol%), CHCl3, rt, 1 h
Ph2SiH2 (1.3 eq), ZnCl2 (2.8 eq),
THF, 65°, 4.5 h
PPh3 (18 mol%), NaHCO3 (70 mol%),
PhSiH3 (140 mol%), Mo(CO)6 (4 mol%),
Ph2HSi, Ph3Si, (C6H11)2EtSi
R3Si = Et3Si, Et2MeSi, n-BuH2Si,
AlCl3 (25 mol%)
R3SiH (1.2-1.5 eq), CH2Cl2,
I (80)
I (95)
I (70)
I (60)
I (5)
I (73)
I (70)
I
O (90)
(80-95)
199
197
197
197
197
197
197
197
188
202
C8
Ph
Ph
Br
Br
Br
CO2H
O
I
Br
Halocarbon
DMSO, Bn3N (1.4 eq), 60°, 3 h
PMHS, (Ph3P)4Pd (5 mol %), MeCN,
DMSO, Bn3N (1.4 eq), 110°, 18 h
PMHS, (Ph3P)4Pd (5 mol %), MeCN,
rt, 10 min
Et3SiH (1.4 eq), PdCl2 (5-10 mol%),
MeC6H5, 95°, 1.0 h
PPh3 (19 mol%), NaHCO3 (140 mol%),
PhSiH3 (200 mol%), Mo(CO)6 (5 mol%),
C6H6, 80°, 2.0 h
PPh3 (33 mol%), NaHCO3 (130 mol%),
PhSiH3 (150 mol%), Mo(CO)6 (8 mol%),
THF, 65°, 4.5 h
PPh3 (20 mol%), NaHCO3 (150 mol%),
PhSiH3 (210 mol%), Mo(CO)6 (5 mol%),
Conditions
Ph
Ph
I (>95)
I (>95)
Br
CO2H
I
O
(37)
(55)
(>95)
(100)
Product(s) and Yield(s) (%)
TABLE 4. ORGANOSILANE REDUCTION OF HALOCARBONS (Continued)
199
199
195
197
197
197
Refs.
203
C10
C9
Cl
O
O
Br
Br
OTf
Br
80°, 4 h
Et3SiH (1.4 eq), PdCl2 (5-10 mol%),
CH2Cl2, 18-20°, 15 min
H(Ph2Si)4H (0.6 eq), AlCl3 (0.25 eq),
CH2Cl2, 18-20°, 15 min
Et3SiH (1.3 eq), AlCl3 (0.25 eq),
K2CO3 (1.8 eq), THF, rt, 12 h
Ph2SiH2 (3 eq), (Ph3P)4Pd (10 mol%),
MeC6H5, 75°, 12.0 h
PPh3 (24 mol%), NaHCO3 (130 mol%),
PhSiH3 (280 mol%), Mo(CO)6 (65 mol%),
THF, 65°, 2.5 h
PhSiH3 (160 mol%), Mo(CO)6 (11 mol%),
Et3N (2 eq), DMF, rt, 40 min
Et3SiH(2.5 eq), Pd(OAc)2, dppp,
Et3SiH (5 eq), AlCl3 (0.1 eq), HCl
C5H12, 40°, 95)
(—)
(>99)
(>95)
II
R-H I + ROSiEt3 II
I (53) + II (6)
I (70)
Product(s) and Yield(s) (%)
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS
R
R-OH
C6-C10
C6
Alcohol
II (7)
144
136
136
Refs.
210
C8
C7
OH
OH
OH
OH
Alcohol
CH2Cl2, 0°, 0.5 h
Et3SiH (x eq), Et3SiD (x eq),
CH2Cl2, rt, 1 h
Ph2ClSiH (2 eq), InCl3 (0.05 eq),
I
I (88)
I
Et3SiH (x mol%), TFA (y mol%), 50°, 15 h
I
I
I (94)
Et3SiH (1 eq), acid, rt, 96 h
C6H14 or CH2Cl2, rt, 20 h
Et3SiH (3.0 eq), (C6F5)3B (5 mol %),
CH2Cl2, rt
Et3SiH (3 eq), AlCl3 (1.5 eq),
HCl, CH2Cl2, rt, 45 min
Et3SiH (2 eq), AlCl3 (1.1 eq),
CH2Cl2, rt, 24 h
Ph3SiH (1.2 eq), TFA (6.5 eq),
Conditions
+
I
x
Solvent
D
4-O2NC6H5
kH/kD 1.05 0.99 1.01 0.98
1.0 0.71 0.5
(56)
(94)
x
12
9
y
1.67
0.2
0.5
(80)
CHCl3
(24)
H2SO4/HOAc TFA
Acid
(>95)
(91)
(78)
Product(s) and Yield(s) (%)
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
133
172
134
134
145
136
136
127
Refs.
211
C9
R
H
OH
OH
OH
OH
3h 3h
ClCH2CH2Cl 80°
OH
Et3SiH, TFA, CH2Cl2
Ph3SiH, TFA, CH2Cl2
BF3, CH2Cl2, rt, 10 min
Ph(t-BuCH2)MeSiH (2-10 mol%),
CH2Cl2, rt, 20 h
Et3SiH (2 eq), BF3•OEt2 (2 eq),
NO2
2h
ClCH2CH2Cl 80°
Br
Time
CH2Cl2
rt
Solvent
Cl
Temp
Ph2ClSiH (2 eq), InCl3 (0.05 eq) R
OH
Et3SiD, CH2Cl2, 0°, 0.5 h
I
(95)
(83)
(70)
D
+
(64)
+
H
II
(50)
D
H
+
+
( —)
H
III
H H IV V I + II + III + IV + V (100), I:II:III:IV:V = 95:5:0:0:0
+
OH
(—)
I + II + III + IV + V (100), I:II:III:IV:V = 83:7:0:6:4
R
H
131
131
126
133
172
133
212
C9
HO
H
OH
SMe
CO2Me
OH
OH
S
OH
Alcohol
ClCH2CH2Cl, 80°, 6 h
Ph2ClSiH (2 eq), InCl3 (5 mol%),
CH2Cl2, rt, 1 h
Ph2ClSiH (2 eq), InCl3 (5 mol%),
ClCH2CH2Cl, 80°, 5 h
Ph2ClSiH (2 eq), InCl3 (5 mol%),
C6H14 or CH2Cl2, rt , 20 h
Et3SiH (3.0 eq), (C6F5)3B (5 mol%),
0°, 1 h; 20°, 3 h
Et3SiH, BF3•OEt2, CH2Cl2,
Et3SiH, TFA, CH2Cl2
Ph3SiH, TFA, CH2Cl2
Conditions
H IV
H
II
+
+
H V
H
I (54)
I (90)
I (0)
S
SMe
CO2Me
I
III
I + II + III + IV + V (100), I:II:III:IV:V = 90:6:3:0:1
+
+
(>95)
(36) + S
SMe
CO2Me (—)
I + II + III + IV + V (100), I:II:III:IV:V = 62:13:7:3:15
I
Product(s) and Yield(s) (%)
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
172
172
172
145
708
131
131
Refs.
213
C10
O OMe
OH
OH
OH
Cl
OH
DCE
InCl3 none AlCl3 BF3•OEt2 DCE InCl3 InCl3 InCl3 InCl3 InCl3 InCl3 InCl3
Ph2ClSi Ph2ClSi Ph2ClSi Ph2ClSi Ph2HSi Et3Si Me2ClSi Ph2ClSi Ph2ClSi Ph2ClSi Ph2ClSi
ClCH2CH2Cl, 80°, 4 h
Ph2ClSiH (2 eq), InCl3 (0.05 eq),
ClCH2CH2Cl, 80°, 4 h
Ph2ClSiH (2 eq), InCl3 (0.05 eq),
MeCN
THF
C6H6
C6H14
DCE
DCE
DCE
DCE
DCE
Solvent
Catalyst
R3Si
R3SiH (2 eq), catalyst (5 mol%), 4 h
CH2Cl2, 0°, 30 min
Et3SiH (2 eq), BF3•OEt2 (2 eq),
ClCH2CH2Cl, 80°, 0.5 h
Ph2ClSiH (2 eq), InCl3 (0.05 eq),
80°
I (74)
I (76)
80°
63°
80°
70°
rt
80°
80°
(0)
(0)
(20)
(33)
(0)
(0)
(19)
(tr)
(5) (23)
80° 80°
(76)
80°
Temp
I
OMe
O
Cl
(0)
(95)
172
172
172
133
172
214
C10
HO
HO
H
H
OH
OH
OH
OH
OH
Alcohol
Et3SiH, BF3, CH2Cl2, rt, 30 min
Et3SiH, BF3, CH2Cl2, rt, 30 min
CH2Cl2, rt, 30 min
Et3SiH (3.3 eq), BF3,
CH2Cl2, 80°, 3 h
Ph2ClSiH (2 eq), InCl3 (0.05 eq),
TFA (5 eq), 0°, 0.5 h; rt, 3 h
Et3SiH (1.3 eq), NH4F (1.3 eq),
Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h
Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h
Conditions
I (86)
I (99)
(68)
(52)
(100)
(100)
I (97)
OH
Product(s) and Yield(s) (%)
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
132
132
126
126, 172
135
173
173
Refs.
215
HO
HO
HO
OH
OH
OH
OH
OH
III (10) +
II (40-45) + IV (40) +
Et3SiH, BF3, CH2Cl2, 5-10 min
II
II (35-40) + IV (35-40) + VI (20-25)
I (15) + II (95:5
(—) + Ph
Ph
3.8
(16) +
1.5 (38)
(49)
(13)
II
Ph2HSi
Ph3SiH, TFA, CH2Cl2, rt, 0.5 h
1.5 (51)
(29)
(20)
II
Ph3Si
1.8
(40)
4.3
(22)
(50)
(28)
II
Et3Si (36)
3.8
(84)
(13)
(3)
I
PhH2Si (24)
4.5
(47)
(42)
(11)
I
Ph2HSi
II
1.8
(34)
(54)
(12)
I
Et2HSi
(n-C8H17)3Si
1.4
(72)
(18)
(10)
I
1.8
IV:III
Ph3Si
Ph
V (41)
+
(64)
Ph
IV (39)
Ph
(21)
Ph
III (20)
IV
H
(15)
Ph
III
H
+ t-Bu
I
I
Alcohol
t-Bu
Ph
Product(s) and Yield(s) (%)
(n-C8H17)3Si
Et3Si
R3Si
CH2Cl2, rt, 0.5 h
R3SiH (1.3 eq), TFA (2.1 eq),
Conditions
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
t-Bu
Ph
V
137
133
24
26
Refs.
227
C17
C16
OH
OH
PMP
OH
N
HO
N
N
Ar
Pr-i CH2CN
SMe
OMe CH2CN
CH2CN
Cl
Ar =
SMe
N
HO
(CO)3Cr
N
Fe
MeO
MeO HO
(22)
8.2 4.3 2.0
8 8.1 7.8
Ph3SiH, TFA, CH2Cl2, rt, 0.5 h
CH2Cl2, rt, 1.5 h
Et3SiH (3 eq), TFA (3 eq),
(18)
8.2
4
N
OMe
N
O
SMe
N
(92)
IV
Cl
OAr
N SMe II
N
Ar
(83)
(92)
(—) only isomer
+
+
CH2CN
N
CH2CN
Pr-i
CH2CN
Ar
PMP
(CO)3Cr
(33)
(34)
(15)
y
I
I 8.3
SMe
N
2
N
Fe
MeO
x
Et3SiH (x eq), TFA (y eq)
Et3SiH (2 eq), TFA, rt, 3 h
Et3SiH (2.7 eq), TFA (7.8 eq), 80°, 2 h
MeO
N
+
SMe III
N N
II + III + IV (—)
N
OAr
24
182
721
179
720
228
C18
Ph
OEt
OMe
OH
Bu-t
OH
Bu-t
N
OH
O
O
Bu-t
OH
OH
Bu-t
Bu-t
Bu-t
H
Ph
Ph OH
Ph
C17 Ph OH
Alcohol
Et3SiH, TFA, CH2Cl2, rt, 16 h
Et3SiH, TFA, CH2Cl2, rt, 16 h
Et3SiH, TFA, CH2Cl2, rt, 16 h
Et3SiH, TFA, 0-5°, 24 h
CH2Cl2, 0°, 30 min
Et3SiH (2 eq), BF3•OEt2 (2 eq),
CH2Cl2, 0°, 30 min
Et3SiH (2 eq), BF3•OEt2 (2 eq),
Conditions
Ph
Ph
Bu-t
Bu-t
OEt
OMe
O
Bu-
t
Bu-t
N
I
O
O
Ph
Bu-t
H
Ph
Ph
(78)
(80)
(31)
(trace)
+
+
Ph II
t-Bu
Ph
(89)
O OEt
Bu-t (38)
I + II (68), I:II = 73:27
Product(s) and Yield(s) (%)
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
153
153
153
722
137
137
Refs.
229
C19
O
R1
Ph
S
(CO)3Cr
MeO
C18-21
N H Cl
OH
Bu-t
OH
OH
Bu-t
OH
R2
O O
N
N
MeO HO
O
OMe OH
EtO2C
HO
N
CH2Cl2, –78°, 12 h; 0°, 10 h
Et3SiH (10 eq), MeSO3H (1 eq),
Et3SiH, TFA, CH2Cl2, rt, 16 h
Et3SiH, TFA, 50°, 48 h
Et3SiH (xs), TFA
Et3SiH (1.1 eq), TFA, rt, 18 h
Et3SiH (xs), TFA, rt, 2 h
OMe
OMe
N H
R1 S
(CO)3Cr
EtO2C
Ph
Bu-t
O
MeO
N
(75)
(86)
Me
H
H
R1
(65)
(—)
(81)
(95)
N
R2
Cl
O O
N
R2
n-C12H25
n-C16H33
n-C15H31
140
153
258
723
486
157
230
O
Ph
MeO (CO)3Cr
OHC
Ph
C19 Ph
O
COH
HO
OH
3
OH
O
O
OH
Alcohol
Et3SiH (4 eq), HOAc, reflux, 40 h
Ph3SiH (3 eq), TFA, rt, 48 h
O
I (80)
I (74)
Ph3SiH (3 eq), TFA, rt, 48 h
Et3SiH (3 eq), HOAc, rt, 48 h
I
3
CH
O
O
O
(89)
I (95)
(59)
Ph
(80)
4-MeC6H4CO2H/HOAc TFA
(82)
(88)
I (98)
(—)
Product(s) and Yield(s) (%)
H2SO4/HOAc
Acid
Ph
(CO)3Cr
MeO
Ph
Et3SiH (1 eq), acid, rt, 30 min
C6H14 or CH2Cl2, rt, 20 h
Et3SiH (3.0 eq), (C6F5)3B (5 mol%),
60°, 4.5 h
Et3SiH (6 eq), TFA (9 eq),
CH2Cl2, rt, 20 h
Et3SiH (1 eq), TFA (17 eq),
Conditions
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
29
26
26
26
134
145
352, 725
724
Refs.
231
HO
C20
S
Ts
Bu-t
R
1:1
Ph
Bu-t
OH
OH
Bu-t
OH
Bu-t
Ph
OH
Bu-t
OH R = Me, Et, n-Pr, n-Bu, n-C5H11
O
t-Bu
n-C13H27
C19-23
Ph
t-Bu
OH
Et3SiH, TFA, CH2Cl2, rt, 16 h
Et3SiH, TFA, CH2Cl2, rt, 16 h
Et3SiH, TFA, CH2Cl2, rt, 16 h
Et3SiH, TFA, 50°, 48 h
Et3SiH, TFA, rt
CD2Cl2, rt, 1 h
Et3SiH (3.2 eq), TFA (5.9 eq),
O
Ph
Bu-t
O
I
(90)
(81)
+
(78)
R
(95)
Bu-t
S (—)
Ts
Bu-t
t-Bu
n-C13H27
Ph
t-Bu
+
Ph
Bu-t
n-C13H27
II
R
I + II (73), I:II = 3:2
S (—)
153
153
153
258
726
128
232
C20
HO
O
O
O
Cl
OH
O
OMe O HO
MeO
O
OH
Alcohol
CO2Et
N
CH2Cl2, –78° to 0°
Et3SiH (3 eq), TFA (3 eq),
Et3SiD, TFA, CH2Cl2, rt, 15 min
Et3SiH, TFA, CH2Cl2, rt, 15 min
Ph3SiH (3 eq), TFA, rt, 48 h
Et3SiH (3 eq), TFA, rt, 48 h
Et3SiH (1.1 eq), TFA, rt, 18 h
Conditions
O
O
O
OMe O
D
I (94)
O
Ph
Ph
OMe
Cl
(75)
(88)
(95)
I (68)
(37)
CO2Et
N
Product(s) and Yield(s) (%)
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
162
64
64
26
26
486
Refs.
233
C22
C21
O
N
Ar
Et3SiH (3 eq), TFA, rt, 24 h O
N N H
CO2Me
OMe
Bz
N
N H H Me
N
I
Bn
N
Bz
N
N Et3SiH, TFA, rt, 4 h
I (60)
(CO)3Cr
(CO)3Cr
(CO)3Cr
i-Pr
Et3SiH, BF3•OEt2, CH2Cl2, –10°, 1 h
Et3SiH, TFA, CH2Cl2, rt, 1 h
Et3SiH, HPF6, CH2Cl2, –30°, 1 h
Et3SiH, HPF6, CH2Cl2, –30°, 0.25 h
Et3SiH, HPF6, CH2Cl2, –30°, 1 h
CO2Me
OH
OH
OH
i-Pr
OMe
Bz
N
Bn
N
Bz H
N
N H Ar = 3,5-(MeO)2C6H3
Ar
N
OH
H HO Me OH
(CO)3Cr
(CO)3Cr
(CO)3Cr
H
(55.5)
(79)
(69)
(65)
(89)
(52)
729
728
174
727
727
727
727
234
C24
C23
C22
O
OH
O OH O
HO CO2Me
H
N
3
N
F
(CO)3Cr
OH
HO
OH
OMe
CO2Me
OBn
OBn
COH
MeO Ar OH OMe Ar = 2,6-(MeO)2C6H3
O
HO
Me
MeO
Alcohol
Et3SiH, TFA, rt, 15 h
Et3SiH, BF3•OEt2, CH2Cl2, –78° to 0°
Et3SiH (4 eq), HOAc, reflux, 24 h
–20°, 24 h
2. Et3SiH (1.5 eq), BF3•OEt2 (1.1 eq),
1. i-Bu2AlH, hexanes, MeC6H5, –78°
Et3SiH, TFA, CH2Cl2, rt
Ph3SiH (3 eq), TFA, rt, 48 h
Conditions
H
N
F
(CO)3Cr
MeO
O
Me
MeO
Ar
O
N
I
HO
(83)
CO2Me
(65)
(87)
+
OBn
OBn
OMe
OMe
OH
O OH O
CO2Me
3
CH
F
(75)
(—)
Product(s) and Yield(s) (%)
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
HO
II
171
I + II (45)
CO2Me
181
29
510
730
26
Refs.
235
C26
C25
Ad
Ad
Ad
Ad
3
N
O
OH
O
OH
OMe
OMe
OH
Se
OH
S
OH
t-BocN
Ph
Ad
Me N
Ad
Ad
Ad
O
Ph
OMe
COH
Et3SiH, TFA (15 eq), CH2Cl2
Et3SiH, TFA, CH2Cl2, –10° to rt, 16 h
2. Et3SiH (3 eq), rt, 1 min
1. HOAc, rt, 24 h
Et3SiH, HOAc
Et3SiH (2.4 eq), TFA, CH2Cl2, rt, 4 h
Et3SiH (2.4 eq), TFA, CH2Cl2, rt, 4 h
Et3SiH (2.3 eq), TFA, CH2Cl2, rt, 3 h
HN
O
H
OMe
OMe
Ad
N
Ad
Me
Ph
Se
I
H
S
I
H
H Ad I
Ad
Ad
I (95)
Ad
Ad
Ad
O
N
O
3
Ad
Ad
II
H
II
H
Ph
OMe
+ Ad
(86)
I (100)
H Ad II
Se
Ad
S
Ad
O Ad
(18)
CH
+
+
+
O Ad
(78)
I + II = (53), I:II = 1:1.8
I + II = (81), I:II = 1:1
I + II = (86), I:II = 2:1
732
731
26
65
160
160
160
236
O
Ad
Ad
Ad
S
Ad
Ad
Ad
Ad
S
Ad
OH
OH
S
OH
OH
Et3SiH (2.4 eq), TFA, CH2Cl2, rt, 4 h
Et3SiH (2.5 eq), TFA, CH2Cl2, rt, 2 h
Et3SiH (2.5 eq), TFA, CH2Cl2, rt, 16 h
I (93)
Ad Ad
S
I
I
H
S
H
H
I
H
Ad I (56)
Ad
Ad
Ad
O Et3SiH (2.4 eq), TFA, CH2Cl2, rt, 2 h
O
Ad
O
Ad
OH
Et3SiH (3.0 eq), TFA, CH2Cl2, rt, 20 h
Conditions
+
+
+
+
Ad
Ad
Ad
Ad II
H
Ad
H
O
H
S
(27)
O
II
Ad II
Ad
Ad
O
I + II (82), I:II = 1:1
I + II (58), I:II = 1:2
I + II (30), I:II = 3 to 1:1
Product(s) and Yield(s) (%)
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
Ad
Ad
C26
Alcohol
160
160
160
160
160
Refs.
237
C28
Ad Ad
CF3
Ad Ad
OMe
Ad Ad
EtO
C27-29
C27
OH
OH
OH
Ph n
OMOM
OH
S
0.52 0.49 0.60 0.41 0.39 5.4
Ph3Si (i-Pr)3Si Et3Si Me2PhSi (TMS)3Si
I:II
I (—) +
0.52
H
n-C6H13H2Si
Ad
Ad
Ph2HSi
R3Si
R3SiH, TFA, CH2Cl2, 3 h
CF3
Ad
Ad
H
H Ad
CF3
Ad
S
159
733
(—)b 161
II (—)
159
159
Ad H Ad II
n = 13 (30)
HO
I + II (—), I:II = 0.53
Ad
+
159
+
H Ad
S
n = 11 (—)
EtO
I + II (—), I:II = 0.32
Ph
+
I + II (—), I:II = 0.72
I
H
n
OMOM
H
S
Ph3SiH, TFA, CH2Cl2, 3 h
Ad Ad
OMe
Ad Ad
EtO
i-Pr3SiH, TFA, CH2Cl2, 3 h
Ph2SiH2, TFA, CH2Cl2, 3 h
Et3SiH, TFA, rt
TFA, CH2Cl2
Et3SiH or PhMe2SiH,
238
Ad
Ad
Ad
Ad
C28-32
C28
(34)
(27)
Me2PhSi
I
(41)
(8)
Et3Si
(74) (79) (57) (94) (83) (66) (77) (71) (85)
5-Me 5-t-Bu 4-Cl 5-Cl 4-F 5-F 4-MeO 3,4,5-Me3
I (—)
H
+
4-Me
Et3SiH, TFA, CH2Cl2, 3 h
Ad
(28)
(0)
(i-Pr)3Si
Ad
(37)
(0)
(9)
(45)
(9)
Ph2HSi Ph3Si
(21) R
(47)
(12)
n-C6H13H2Si
(Me3Si)3Si
(—)
(—)
None
H I
R3Si
Ad II
Ad
Ad Ad
(54)
(31)
(40)
(58)
(49)
(38)
(36)
(91)
Ad III
Ad
OMe + MeO
H
R
Ad
II
(17)
(9)
(11)
(14)
(15)
(8)
(5)
(9)
IV
H II
+
+
Product(s) and Yield(s) (%)
I
R3SiH, TFA, CH2Cl2, –10° to rt, 16 h
Conditions
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
H
OH R
R
OH
OMe
Alcohol
I:II = —
Ad
Ad
O
Ad
III
O
159
CF3 158
IV
OH
O
Refs.
239
MeO
Ad
X
OH
OBn
OBn OEt
Ad R, X = H, H; Me, i-Pr
R H HO
C29-33
C29
Et3SiH (large xs), TFA
Et3SiH, TFA, CH2Cl2, 0°, 2 h
R H
MeO
H
Ad Ad
X (—)
OBn
OBn OEt (76)
734
168
240
C32
C31
Ad
Ad
Ad
t-Bu
OH
Ad
Bu-t
OH
Alcohol
I
23
(TMS)3Si
I:II 2.9 5.8 1.6 NR 6.2 2.5 1.2
R3Si n-C6H13H2Si Ph2HSi Ph3Si (i-Pr)3Si Et3Si Me2PhSi (TMS)3Si
R3SiH, TFA, CH2Cl2, 24 h
4.1
Me2PhSi
H
21 3.4
Et3Si
Ad
2.5
(i-Pr)3Si
+
1.3
Ph3Si
Ad
Ad
t-Bu
0.74
n-C6H13H2Si
Bu-t
H
Ad
Ph2HSi
Ad I
+
I:II
Ad
Ad
t-Bu
Ad
II
H
II
H
t-Bu (—)
Product(s) and Yield(s) (%)
R3Si
R3SiH, TFA, CH2Cl2, 3 h
Conditions
TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)
(—)
159
159
Refs.
241
C57
O
O N H
H N
O N H
product ratios were observed for this reaction.
O
O
NH
Et3SiH, TFA
O HO
OH
CO2H
NH
OH
The yield was determined by gas chromatography.
b Various
a
H 2N
H N
Ph
HO
O
H2N
O
H N
O
HN
HN
HN
NH
NH2
NH
O
O
OH
H2N O
H N
O N H
Ph H N O HO
HO
O
(—)
N H
NH CO2H
O
H2N
O
O
O
NH
OH
H N
O
HN
HN
HN
NH
NH2
NH
O
OH O
169
242
C8
C7
C6
C5
O
O
O
Ph
Et
O
O
O
O
OMe
OSiEt3
O
Ether
CH2Cl2, rt, 20 h
Et3SiH (1.1 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (3.0 eq), (C6F5)3B (5 mol%),
C6H14, rt, 20 h
Et3SiD (1.5 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h; then TBAF
Et3SiH (3.0 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (1.1 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h; then TBAF
Et3SiH (3.0 eq), (C6F5)3B (10 mol%),
reflux, 24 h
Et3SiH (2 eq), TFA (10 eq),
CH2Cl2, rt, 20 h
Et3SiH (1.1 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (1.1 eq), (C6F5)3B (10 mol%),
CH2Cl2, rt, 20 h
Et3SiH (3.0 eq), (C6F5)3B (5 mol%),
Conditions
D Ph
OH
OSiEt3
OH
OH
(88)
(>99) + CH4
(91)
(>99)
(78)
(—) 41% ee
(79)
(60)
(>95) + C3H8
OH
(97)
Product(s) and Yield(s) (%)
OSiEt3
OH
OSiEt3
TABLE 6. ORGANOSILANE REDUCTION OF ETHERS
145
145
145
145
145
144
271
144, 145
144, 145
144, 145
Refs.
243
C11
C10
C9-16
C9
EtO2C
RO
OMe
3
O
OMe
OEt
THF, rt, 3-5 h
PMHS (2 eq), (Ph3P)4Pd (0.01 eq),
CH2Cl2, rt, 20 h
Et3SiH (1.1 eq), (C6F5)3B (5 mol%),
THF, rt, 3-5 h
PMHS (2 eq), (Ph3P)4Pd (0.01 eq),
CH2Cl2, rt, 20 h
Et3SiH (1.1 eq), (C6F5)3B (5 mol%),
reflux, 24 h
Et3SiH (2 eq), TFA (10 eq),
(92) (85) (89) (85) (90)
THPO(CH2)4 AcO(CH2)4 MOMO(CH2)4 TBSO(CH2)4
EtO2C
(87)
TsO(CH2)4
OH
(86)
(96) + CH4
(90)
PMBO(CH2)4
OSiEt3
(92)
BnO(CH2)4
(92) (88)
(90)
4-FC6H4
PrenylO(CH2)4
(89)
2-C10H7 (90)
(85)
2-i-Pr-4-Me-c-C6H9
4-NO2C6H4
(87)
Ph2CH
4-MeOC6H4
(94)
PhMeCH
(>99) + CH4
(7)
Ph(CH2)3
R
ROH +
OSiEt3
OH
270
145
270
145
271
244
C12
C11
OMe OMe
OMe
OMe
OMe
OMe
OMe
Ether
CH2Cl2, rt, 6 h
Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 24 h
Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 6 h
Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 24 h
Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 10 h
Et3SiH (1.3 eq), BF3•OH2 (4-6 eq),
CH2Cl2, rt, 24 h
Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 10 h
Et3SiH (1.3 eq), BF3•OH2 (4-6 eq),
Conditions
OMe
OMe
D
OMe
I (26)
D
I
D
D
D
D
D
(37)
(100)
(100)
(100)
(100)
(100)
Product(s) and Yield(s) (%)
TABLE 6. ORGANOSILANE REDUCTION OF ETHERS (Continued)
262
262
262
262
217
262
217
Refs.
245
SMe
SMe
MeO
MeO
MeO
OMe
OMe
OMe
OMe
OMe
OMe
OMe
CH2Cl2, 0°, 24 h
Et3SiH (3-5 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 24 h
Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 144 h
Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 48 h
Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 6 h
Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 37 h
Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 24 h
Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),
CH2Cl2, rt, 24 h
Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),
I (100)
SMe
I (50)
MeO
I (95)
MeO
I
D
D
I
D
D
(24)
(80)
(100)
D
D
D
(65)
(60)
263
262
262
262
262
262
262
262
246
C14
C13
C12
TBSO
NMe2
Fe
Ac
N
O
O
SMe OMe
OMe
OMe
Ether
reflux, 24 h
Et3SiH (2 eq), TFA (10 eq),
CH2Cl2, rt, 20 h
Et3SiH (3.0 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (1.1 eq), (C6F5)3B (5 mol%),
CH2Cl2, –40°, 1-2 h
Et3SiH (2 eq), BF3•OEt2 (2 eq),
CH2Cl2, rt, 24 h
Et3SiH (6.4 eq), BF3•OEt2,
Et3SiH (2 eq), TFA, rt, 20 min
CH2Cl2, 0°, 24 h
Et3SiH (3-5 eq), BF3•OEt2,
Conditions
I (86)
I
TBSO
NMe2
Fe
SMe
Ac
N
OH
(77) +
(3)
(97)
(100)
(88)
(70)
OSiEt3
Product(s) and Yield(s) (%)
TABLE 6. ORGANOSILANE REDUCTION OF ETHERS (Continued)
(93)
271
145
145
521
262
179
263
Refs.
247
C20
C16
C15
n-C10H21
O
O
O
O
O
N H
O
O
CO2H
OBu-t
O N H CO2H
C10H21-n
OPr-i
O
O
OBu-t
rt, 35 min
Et3SiH (2.5 eq), TFA, CH2Cl2,
CH2Cl2, rt, 20 h
Et3SiH (3.0 eq), (C6F5)3B (10 mol%),
CH2Cl2, rt, 20 h
Et3SiH (1.1 eq), (C6F5)3B (10 mol%),
reflux, 24 h
Et3SiH (2 eq), TFA (10 eq),
THF, rt, 3-5 h
PMHS (2 eq), (Ph3P)4Pd (0.01 eq),
CH2Cl2, rt, 45 min
Et3SiH (2.5 eq), TFA,
OH
HO
N H
O
O
(60)
CO2H
OH
(85)
(96) + Me3CH
I (>99)
I
O
O N H
CO2H
(100) + Me3CH
OH
n-C10H22 (93) + n-C10H21OSiEt3 (95)
O
O
O
O
307
144
144
271
270
307
248
C21
C20
O
O
Fe
O
O
HO
H
O
O
O
O
O
Ph
OH
OH
Ether
O
O
O
O
Et3SiH (4 eq), TFA, rt, 3 h
2. Et3SiH (23 eq), rt, 16 h
0°, 30 min
1. BF3•OEt2 (2.25 eq), CH2Cl2,
2. Et3SiH (13.9 eq), rt, 16 h
0°, 1 h
1. BF3•OEt2 (2.25 eq), CH2Cl2,
Conditions
O
O
O
Fe
O
HO
HO
O
O
O
Ph
O
(80)
O
(44)
HO
HO
OH
O
O
OH OH
OH
O
O
+
(36)
Product(s) and Yield(s) (%)
TABLE 6. ORGANOSILANE REDUCTION OF ETHERS (Continued)
OH
O
(44)
179
735
735
Refs.
249
C25
C23
C22
Ph
Ph
MeO
MeO
Ph
OBu-t
O
H
O
O
O
CO2H
OBu-t
OH
OMe
OMe
Et3SiH, TFA
Et3SiH (3 eq), HOAc, rt, 48 h
CH2Cl2, rt, 15 min
Et3SiH (2.5 eq), TFA,
0°, 1 h; rt, 16 h
BF3•OEt2 (1.5 eq), CH2Cl2,
Et3SiH (4.5 eq), MeO
MeO
I (45)
Ph
Ph
MeO
I
H
MeO
Ph
OMe H
OH
O
(80)
O
OMe
OH
OH
O
OH
OH
+
OMe (3)
OMe
484, 736
272
26
CO2H (99) + Me3CH 307
OH
(66)
250
C32
C30-44
(93) (89) (93)
1 min, 16 sec 4 min 24 min
0.01 0.01 0.01
MPM TBDPS MOM
AcO AcO
TrO
AcHN
O OMe
CH2Cl2, rt, 32 min
Et3SiH (3.6 eq), TMSOTf (0.01 eq),
CH2Cl2, rt, 20 h
Et3SiH (3.0 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
OH + Ph3CH
Product(s) and Yield(s) (%)
AcO AcO
HO
I (95)
I
AcHN
O OMe
(86) + Ph3CH
n-C16H34 (98) + n-C16H33OSiEt3 (98)
(93)
1 min, 20 sec
0.01
Bn
Et3SiH (1.1 eq), (C6F5)3B (5 mol%),
(95)
3 min, 30 sec
0.01
Bz
C16H33-n
(99)
2 min
0.02
Piv
O
(96)
Time
8
4 min, 30 sec
RO
0.005
Et3SiH (1.2 eq), Et3SiOTf (x eq),
Ac
OTr
R
8
Conditions
TABLE 6. ORGANOSILANE REDUCTION OF ETHERS (Continued)
CH2Cl2, rt x
n-C16H33
RO
Ether
269
145
145
269
Refs.
251
C92
C90
C47
C42
TrO
BnO BnO
TrO
BzO BzO
TrO
BnO BnO
BnO
TrO BnO
BzO BzO
TrO
OMe
O
BnO
O
BzO
O
O
BnO
O
OTr
OMe
OMe
BnO
BnO
O
AcHN
O
O
OBz
O OTr OBn OBn OTr
OBz
CH2Cl2, rt, 40 min
Et3SiH (2.5 eq), Et3SiOTf (0.01 eq),
CH2Cl2, rt, 5 min
Et3SiH (1.2 eq), Et3SiOTf (0.01 eq),
CH2Cl2, rt, 11 min
Et3SiH (1.2 eq), TMSOTf (0.01 eq),
CH2Cl2, rt, 5 min
Et3SiH (1.2 eq), TMSOTf (0.01 eq),
CH2Cl2, rt, 65 min
Et3SiH (1.2 eq), Et3SiOTf (0.01 eq),
CH2Cl2, rt, 32 min
Et3SiH (1.2 eq), TMSOTf (0.01 eq),
HO
BnO BnO
HO
BzO BzO
HO
BnO BnO
BnO
HO BnO
O OMe
O
BnO
O
BzO
O
BnO
BnO
O
(96)
O
BnO
(86)
O
OBz
O
OH + Ph3CH
+ Ph3CH
OBn OBn OH
OBz
(88) + Ph3CH
(89) + Ph3CH
(99) + Ph3CH
OH
OMe
OMe
Ph3CH
O
I
AcHN
I (92) +
BzO BzO
HO
269
269
269
269
269
269
252
C11
C10
AcO
AcO
AcO
AcO
O
H 2N
Ph
OAc
CO2H
S
O
O
[(p-tol)3P]4Pd, 5 h
Ph2SiH2 (2 eq), ZnCl2 (1.9 eq),
I
O
O
O
[(p-tol)3P]4Pd, 4 h
Ph2SiH2 (2 eq), ZnCl2 (2.4 eq),
I OAc
CN
CN
CN
CN
OEt I OAc
OAc
O
OAc
OEt
[(p-tol)3P]4Pd, 3 h
Ph2SiH2 (2.1 eq), ZnCl2 (1.8 eq),
I
+
(87)
+
(—)
+
+
+
+ OMe
II
O
II OAc
O
CN
CN
OEt II OAc
O
II CO2Me
O
OAc
I + II (63), I:II = 75:25
I + II (68), I:II = 50:50
I + II (92), I:II = 44:56
I + II (75), I:II = 33:67
II
(—)
Product(s) and Yield(s) (%)
I + II (98), I:II = 1:1
CO2H
S
OMe
OAc
N
OH
O
[(p-tol)3P]4Pd, 2 h
Ph2SiH2 (2.5 eq), ZnCl2 (2.1 eq),
THF, rt, 4 d
PMHS (2.0 eq), (Ph3P)4Pd (4.0 mol%),
Et3SiH, TFA, CH2Cl2, BF3•OEt2
H2N
Ph
O
OMe
OAc
THF, rt, 3-5 h
O
CO2Me
O
OAc
N
O
PMHS (2 eq), (Ph3P)4Pd (0.01 eq),
Conditions
TABLE 7. ORGANOSILANE REDUCTION OF ALLYL ESTERS
I CO2Me
O
Allyl Ester
273
273
273
273
196, 273
275
270
Refs.
253
C12
AcO
AcO
Ph
Ph I
AcO
Ph
THF, rt, 13 h; 50°, 2 h
(Ph3P)4Pd (12.0 mol%),
Ph2SiH2 (3.5 eq), ZnCl2 (3-4 eq),
[(p-tol)3P]4Pd, 24 h
Ph2SiH2 (4 eq), ZnCl2 (2.2 eq),
I (90)
I
O
OAc
O
OEt OAc
I
OAc
OEt
O
[(p-tol)3P]4Pd, 3 h
+
CN
(93)
(58)
+
I + II (100), I:II = 6:4
Ph
I + II (99), I:II = 1:1
O Ph2SiH2 (1.7 eq), ZnCl2 (2 eq),
I I + II (99), I:II = 1:1
OAc
THF, 20 min
PMHS (2.2 eq), (Ph3P)4Pd (4.6 mol%),
THF, 0°, 24 h
Ph2SiH2 (2.0 eq), (Ph3P)4Pd (10 mol%),
THF, rt, 24 h
PMHS (2.1 eq), (Ph3P)4Pd (4.0 mol%),
(Ph3P)4Pd (7.2 mol%), THF, rt, 30 h
Ph2SiH2 (2.0 eq), ZnCl2 (3-4 eq),
THF, rt, 5 d
PMHS (1.7 eq), (Ph3P)4Pd (5.0 mol%),
PPh3 (20 mol%), THF, 5 d
PMHS (1.75 eq), (Ph3P)4Pd (6 mol%),
OAc
CN
OAc
OAc
OAc
II
O
+
II
OEt
OAc
Ph
(52)
I + II (55), I:II = 25:75
I + II (79), I:II = 6:1
II
(48)
196
273
273
273
196
196
196
196
273
254
C13
C12
OAc
AcO
O
O
O
OAc
OAc
OAc
O
OAc
CN
OAc
CN
THF, 48 h
PMHS (2.5 eq), (Ph3P)4Pd (3.5 mol%),
THF, 1.5 h
PMHS (1.8 eq), (Ph3P)4Pd (3 mol%),
THF, rt, 3-5 h
PMHS (2 eq), (Ph3P)4Pd (0.01 eq),
[(p-tol)3P]4Pd, 80 h
Ph2SiD2 (2.7 eq), ZnCl2 (8.4 eq),
[(p-tol)3P]4Pd, 120 h
Ph2SiH2 (2 eq), ZnCl2 (4 eq),
[(p-tol)3P]4Pd, 24 h
Ph2SiD2 (4 eq), ZnCl2 (8 eq),
D N Boc
AcO
AcO
AcO
D
O
OH
O
OAc
O
OAc
O
OAc
O
D
O [(p-tol)3P]4Pd, 24 h
OAc Ph2SiD2 (2.6 eq), ZnCl2 (5.4 eq),
Conditions
I
CN
+
(100)
+
(—)
I + II (75), I:II = 10:1
CN
(85)
(10)
(26)
(42)
(59)
Product(s) and Yield(s) (%)
TABLE 7. ORGANOSILANE REDUCTION OF ALLYL ESTERS (Continued) OAc
OAc
N Boc
AcO
AcO
AcO
Allyl Ester
II
CN
273
273
270
273
273
273
273
Refs.
255
C15
C14
Ph
AcO
Ph
OAc
OAc
OAc
O
O
n-C8H17
AcO
O
O
O O
[(p-tol)3P]4Pd, 10 h
Ph2SiH2 (3.3 eq), ZnCl2 (5 eq),
Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h
Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h
THF, rt, 1.5 h
PMHS (3.7 eq), (Ph3P)4Pd (8.0 mol%),
[(p-tol)3P]4Pd, 4 h
Ph
Ph
O
O
n-C8H17
I
O Ph2SiH2 (2 eq), ZnCl2 (1.9 eq),
I
CN
O
I (100)
OAc
(Ph3P)4Pd (12.0 mol%), THF, rt, 4 h
Ph2SiH2 (3.5 eq), ZnCl2 (3-4 eq),
THF, rt, 30 h
Ph2SiH2 (2.2 eq), (Ph3P)4Pd (7.2 mol%),
THF, rt, 48 h
PMHS (2.5 eq), (Ph3P)4Pd (3.5 mol%),
OAc
CN
OAc
CN
OAc
O
I
O
O
(92)
O
+
(63)
(48) +
(74)
+
CN
II
O
II OAc
CN
(75)
H
O O
(12)
I + II (65), I:II = 50:50 O
I + II (73), I:II = 1:1
273
173
173
196, 273
273
196
196
196
256
C17
C16
C15
Ph
Ph
AcO
AcO
Ph
O
O
Bz
Bz
O
OAc
OAc
OAc
CO2Et
O
O
Allyl Ester
Br
THF, rt, 1 h
Ph2SiH2 (1.9 eq), (Ph3P)4Pd (5.7 mol%),
THF, 1.5 h
PMHS (1.8 eq), (Ph3P)4Pd (3 mol%),
Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h
[(p-tol)3P]4Pd, 4 h
Ph2SiH2 (2.9 eq), ZnCl2 (2.4 eq),
[(p-tol)3P]4Pd, 4 h
Ph2SiH2 (2.9 eq), ZnCl2 (2.4 eq),
[(p-tol)3P]4Pd, 10 h
Ph2SiD2 (3.7 eq), ZnCl2 (16.9 eq),
Conditions
I
I
I
O
Bz
Bz
CO2Et
O
O
O
D
+
(89)
+
I + II (90), I:II = 1:1
Ph
Ph
Ph
O
Ph
O
+
Ph
CO2Et
Bz
Bz
(5)
II
Br
I + II (79), I:II = 50:50
I + II (79), I:II = 50:50
I + II (89), I:II = 1:1
Br
+
O
II
II
(55)
Product(s) and Yield(s) (%)
TABLE 7. ORGANOSILANE REDUCTION OF ALLYL ESTERS (Continued)
196
196, 273
173
273
273
273
Refs.
257
C40
C26
C20
C18
MeO2C
Bz
O
O
Bz
O
O
NBn2
O
O
NHCbz
O
OAc
MeO2C AcO
TBSO
Ph
AcO
AcO
O O OAc
OAc Et3SiH, TMSOTf, CH2Cl2, 0-20°, 23 h
THF, rt, 3-5 h
PMHS (2 eq), (Ph3P)4Pd (0.01 eq),
THF, rt, 3-5 h
PMHS (2 eq), (Ph3P)4Pd (0.01 eq),
[(p-tol)3P]4Pd, 6 h
Ph2SiH2 (1.6 eq), ZnCl2 (2.4 eq),
Ph
Bz +
MeO2C O
O
O
NBn2
II
O OAc
(87)
+
O
OAc
O
OAc
II
(85)
O
OH
OH
NHCbz
O
+ Bz
MeO2C AcO
TBSO
I
O
OAc
I
O
[(p-tol)3P]4Pd, 4 h
O Ph2SiH2 (1.4 eq), ZnCl2 (2.4 eq),
OAc
OAc
+
Bz
Bz
(16)
(—)
(—)
I + II (91), I:II = 50:50
I + II (94), I:II = 50:50
737
270
270
273
273
258
C7-10
C7
C5
Ar
F
t-Bu
O
O
OH
O
O
OH
OH
OH
Carboxylic Acid
THF, rt
PMHS (3 eq), TBAF (2 mol%),
A, 150-170°
B, >180°
Et3SiH (xs), TFA, TFAA, 60°, 5 h
2. Add acid, 18 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 201 (1 mol%),
TFAA, 60°, 5 h
Ph2SiH2 (2 eq), TFA (10 eq),
TFAA 60°, 5 h
Et3SiH (2 eq), TFA (10 eq),
Conditions
Ar
I (60)
F
I (80)
t-Bu
O H
(72)
(30)
(70)
(74) (67) (69) (75) (78) (70) (72) (79)
4-ClC6H4 2,4-Cl2C6H3 3,5-Cl2C6H3 3-MeC6H4 4-MeC6H4 2,4-Me2C6H3 3,4,5-(MeO)3C6H2
(82) 4-BrC6H4
Ph
Ar
(46)
O2CCF3
OH
O2CCF3
OH
I
I
Product(s) and Yield(s) (%)
TABLE 8. ORGANOSILANE REDUCTION OF ACIDS
278
284
284
277
280
277
277
Refs.
259
C7-18
C7-11
R
R
Ar
O
O
O
OH
OH
OH
THF, 16 h
PMHS (10 eq), Ti(OEt)4 (100 mol%),
CH2Cl2, rt, 20 h
Et3SiH (6 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (3.3 eq), (C6F5)3B (5 mol%),
R
RMe
Ar
OH
OSiEt3 (93) (94) (91) (96)
4-BrC6H4 4-IC6H4 4-MeC6H4 2-C10H7
(86) (88) (94) (91)
Bn(CH2)3 Bn(CH2)4 n-C11H23 n-C17H35
(78) (81) (81) (86)
4-O2NC6H4 4-HOC6H4 Bn n-C17H35
Ph
(92)
(37)
Bn(CH2)2
R
(91)
BnCH2
Ph (85)
(93)
4-FC6H4
R
(95)
Ph
Ar
279
281
281, 282
260
C10
C9
C8
C7-18
O
O
O
O
OH
OH
n-C9H19
Ph
Ph
Ar
R
O
OH
OH
OH
Carboxylic Acid
2. Add acid, 6 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
A, 150-170°
B, >180°
2. Add acid, 0.5 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
CH2Cl2, rt, 20 h
Et3SiH (6.0 eq), (C6F5)3B (5 mol%),
Et3SiH (xs), TFA, TFAA, 60°, 5 h
Ti(OPr-i)4 (14 mol%), THF
PMHS (10 eq),
Conditions
(86) (69) (76) (70) (88)
30 h 48 h 30 h 16 h
4-MeC6H4 4-MeOC6H4 2-MeOC6H4 n-C17H35
O
4-MeC6H4
OH
H
OH
(63)
16 h
16 h
Ph 4-O2NC6H4
Time
R
(80)
(50)
(72)
(94)
(45)
4-MeOC6H4 (97)
Ar
I
OH
n-C9H19
I (65)
Ph
Ph
Ph
ArMe
R
Product(s) and Yield(s) (%)
TABLE 8. ORGANOSILANE REDUCTION OF ACIDS (Continued)
280
284
284
280
282
283
279
Refs.
261
C17
C12
C11
n-C16H33
Ph
n-C10H21
Ph
Ph
O
O
OH
OH
O O
O OH
OH
OH
CH2Cl2, rt, 20 h
Et3SiH (6.0 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (6.0 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (6.0 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (6.0 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (6.0 eq), (C6F5)3B (5 mol%), I
n-C17H36
Ph
n-C11H24
Ph
Ph
(94)
(91)
+
(93)
(93)
II
I + II (—), I:II = 37:63
282
282
282
282
282
262
C7
C3
C2-12
Ph
Ph
EtS
R
O
O
Br
Cl
Cl
Cl
O
O
Acyl Halide
(86) (90) (91) (87) (86) (90) (82) (80)
PhCH=CH 4-O2NC6H4 4-MeOC6H4 2-C4H3O 2-C4H3S Br(CH2)3 Cl(CH2)3 EtO2C(CH2)8
286 109
286
711
281
286
286
I (45)a
(91)
(—)
109
I (—)
Cl
(87)
BnCH2
109
Refs.
A, rt
I (—)
Ph
SiCl3
(90)
Ph
(>95)a
(—)
(—)
t-Bu
Me
R
Product(s) and Yield(s) (%)
Et3SiH, Et2O, reflux
Bn3SiH, Et2O, reflux
MeCN, rt, 1 h; 85°, 0.5 h
Cl3SiH (3 eq), (n-Pr)3N (1 eq),
CH2Cl2, rt, 20 h
I (—)
H
H
PhMe (84)
I
O
O
H
Et3SiH (6 eq), (C6F5)3B (5 mol%),
Ph
EtS
R
O
Et3SiH, AlCl3, Et2O, reflux
Bn3SiH, Et2O, reflux
A, rt
C, rt
Conditions
TABLE 9. ORGANOSILANE REDUCTION OF ACYL HALIDES
263
C9
C8
C7
EtO
Cl
Cl
Cl
O
Cl
Cl
X = Cl, Br
X Bn3SiH, Et2O, reflux
C, rt
C, rt
A, rt
C, rt
EtO
H
H
I (89)
H
O
O
O
O
Cl
C, rt
O N
Cl
Cl
O
Et3SiH, AlCl3, Et2O, reflux
O
O
O
Cl
O
O
Cl
O
H
H
H
I
I
N
O
O
Cl
O
O
O
O
I
O
H
H
H
(15)a
H
(—)
(—)
(>95)a
(85)
(89)
286
109
109
109
109
109
286
264
C22
C16
C14
C11
C10
a
O
Cl
O
O
Cl
Cl
Cl
O
8
O
Cl OMe Et3SiH, TFA, CCl4, 15 min
CH2Cl2, rt, 20 h
Et3SiH (4 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (4.0 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 20 h
Et3SiH (2.2 eq), (C6F5)3B (5 mol%),
C, rt
Conditions O 8
n-C16H34
n-C14H30
H
O
O
(95)
(97)
OSiEt3
H
H
OMe
(95)
(85)
(—)
Product(s) and Yield(s) (%)
TABLE 9. ORGANOSILANE REDUCTION OF ACYL HALIDES (Continued)
The yield was determined by NMR analysis.
n-C15H31
n-C13H27
Cl
O
Acyl Halide
285
281
282
281, 282
109
Refs.
265
C4
O
O
O
OEt
Ester
(1.5-3.0 mol%), C6D6, rt, 25 min
PhSiH3 (1.2 eq), Mn(CO)5Br
Et3SiH (2.2 eq), 201 (0.2 mol%), rt, 26 h
(3.0 mol%), C6D6, hν, 20°, 35 min
Ph2SiH2 (1.2 eq), Mn(CO)5SiMe2Ph
(1.5-3.0 mol%), C6D6, rt, 4 h
Ph2SiH2 (1.2 eq), Mn(CO)5Ac
(1.5-3.0 mol%), C6D6, rt, 4 h
Ph2SiH2 (1.2 eq), Mn(CO)4PPh3Ac
(1.5-3.0 mol%), C6D6, rt, 4 h
PhSiH3 (1.2 eq), Mn(CO)5Br
(1.5-3.0 mol%), C6D6, rt, 1.5 h
PhSiH3 (1.2 eq), Mn(CO)5Ac
(1.5-3.0 mol%), C6D6, rt, 15 min
PhSiH3 (1.2 eq), Mn(CO)4PPh3Ac
(3.0 mol%), C6D6, rt, 1.75 h
Ph2MeSiH (1.2 eq), Mn(CO)5Ac
Conditions (84)
+
O (35)
EtOEt ( 99:1
O
O
I (83) cis:trans = 10:90
O
I (90)
O
(79) cis:trans > 99:1
(84) cis:trans = 12:88
(87)
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
306
306
306
306
306
306
Refs.
271
C7
HO
O
O
O
O
O
O
O
O
OH
O
O
OMe
OMe
OEt , SbCl5, TMSCl, SnI2, CH2Cl2, –78°, 30 min
OEt , TrSbCl6(5-30 mol%),
OEt , SbCl3,
OEt , SbCl5, TMSCl, SnI2, CH2Cl2, –78°, 30 min
OEt , TrSbCl6(5-30 mol%),
THF, 65°, 0.5 h
(MeO)3SiH (3.5 eq), LiOMe (6 mol%),
THF, 65°, 9.5 h
(MeO)3SiH (3.5 eq), LiOMe (6 mol%),
(EtO)3SiH (2.2 eq), CsF (1 eq), rt, 1 min
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1.
OTBS
2. Et3SiH (1.5 eq), –23°, 2.5 h
1.
OTBS
TMSCl, SnI2, CH2Cl2
Et3SiH,
OTBS
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1.
OTBS
2. Et3SiH (1.5 eq), –23°, 2.5 h
1.
OTBS
I
OEt
I
O OEt
OEt
HO
HO
OH
OH
I (89) cis:trans > 99:1
O
O
O
I (82) cis:trans = 4:96
O
O
(50)
OH
(63)
(100)
OH
(82) cis:trans > 99:1
(84)
(87) cis:trans = 7:93
294
294
81
306
306
306
306
306
272
C7
S
S
O
O
O
CO2Et
O
O
O
OEt
Ester
OEt , SbCl5, TMSCl, SnI2,
OTBS
OEt , TrSbCl6 (5-30 mol%), CH2Cl2, –78°, 30 min
OEt , SbCl5, TMSCl, SnI2,
OEt , TrSbCl6 (5-30 mol%), CH2Cl2, –78°, 30 min
MeC6H5, rt
Ph3SiH, (C6F5)3B (1 mol%),
2. Et3SiH (1.5 eq), –23°, 2.5 h
1.
OTBS
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1.
OTBS
2. Et3SiH (1.5 eq), –23°, 2.5 h
1.
OTBS
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1.
rt, 0.5-2 h
2. (EtO)3SiH (2 eq), ester addition,
THF, –15°, 15 min
1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),
Conditions
I
O
OH
OEt
I
O
OEt
S
CHO
S
(45)
I (81) cis:trans > 99:1
O
(85) cis:trans > 99:1
(91) cis:trans > 99:1
(75)
I (86) cis:trans > 99:1
O
O
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
116
306
306
306
306
290
Refs.
273
C7-28
C7-9
R1
R1
O
O
OR2
R2
R3Si Ph2HSi (EtO)2MeSi (EtO)3Si Ph2HSi (EtO)3Si Ph2HSi (EtO)2MeSi (EtO)3Si (EtO)2MeSi (EtO)3Si Ph2HSi (EtO)2MeSi (EtO)3Si (EtO)3Si Ph2HSi (EtO)2MeSi (EtO)3Si (EtO)3Si (EtO)3Si (EtO)3Si
R2 Et Et Et Et Et Me Me Me Et Et Me Me Me Me Me Me Me menthyl menthyl menthyl
R1 n-C4H9 n-C4H9 n-C4H9 Ph Ph MeO2C(CH2)7 MeO2C(CH2)7 MeO2C(CH2)7 n-C11H23 n-C11H23 H2C=CH(CH2)8 H2C=CH(CH2)8 H2C=CH(CH2)8 H2C=CH(CH2)8 n-C8H17CH=CH(CH2)7 n-C8H17CH=CH(CH2)7 n-C8H17CH=CH(CH2)7 H2C=CH(CH2)8 H2C=CH(CH2)8 n-C8H17CH=CH(CH2)7
R3SiH (x eq), CsF (1 eq)
(EtO)3SiH (1.5 eq), HAp, rt
x
2.2
2.2
2.2
2.2
2.2
1.1
2.2
2.2
2.2
1.1
2.2
2.2
2.2
2.2
1.1
2.2
1.1
2.2
2.2
1.1
rt
60°
rt
rt
120°
140°
60°
rt
80°
140°
60°
100°
rt
120°
140°
100°
140°
rt
120°
140°
Temp
R2
R2
R1
Time
+
Ph OH
72 h
9h
72 h
4h
3h
4h
0.5 h
20 h
48 h
10 h
0.5 h
20 h
12 h
2h
4h
3h
4h
1 min
3h
4h
(80)
(75)
(75)
(90)
(85)
(70)
(70)
(65)
(65)
(70)
(90)
(90)
(65)
(65)
(65)
(65)
(65)
(90)
(90)
(90)
EtO
20 h
n-C5H11 MeO 24 h
R1
I
O
Time
R1
R1
R2
(97)
(44)
R1 II
R2
81
353
274
C8
Br
O
O
O
O
O
O
O
O
O
OEt
CF3
OMe
O
O
O
O
OEt
OMe
Ester
ester addition, –20° to rt, 8 h
2. (EtO)3SiH (2 eq),
THF, –15°, 15 min
1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),
ester addition, rt, 0.5-2 h
2. (EtO)3SiH (3.3 eq),
THF, –15°, 15 min
1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),
TBAF/alumina (1 mol%), MeC6H5, rt
PMHS (5 eq), Cp2TiF2 (2 mol%),
TBAF/alumina (1 mol%), MeC6H5, rt
Cp2Ti(OC6H4Cl-4)2 (2 mol%),
PMHS (5 eq),
TBAF/alumina (1 mol%), MeC6H5, rt
Cp2Ti(OC6H4Cl-4)2 (2 mol%),
PMHS (5 eq),
TBAF/alumina (1 mol%), MeC6H5, rt
PMHS (5 eq), Cp2TiF2 (2 mol%),
EtCl2SiH (2 eq), AlBr3 (1 eq), 20°, 2 h
MeC6H5, 100°, 16 h
Et3SiH, EtI, Et2NH, [RuCl2(CO)3]2,
Conditions
Br
O
OH
I
O
OH
O
OH
I (76)
HO
I
(69)
OH
(89)
(75)
OMe
OSiEt3
(78)
OH
+
OH
(92)
(78)
(88)
OH
OH (14)
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
290
290
301
301, 302
302
301
192
299
Refs.
275 O
O
OMe
OMe
EtI, Et2NH, MeC6H5, 100°, 16 h
Et3SiH (1.5 eq), [RuCl2(CO)3]2,
40-55°, 16 h
(EtO)3SiH (2.5 eq), Ti(OPr-i)4 (5 mol%),
ester addition, rt, 0.5-2 h
2. (EtO)3SiH (2 eq),
THF, –15°, 15 min
1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),
n-BuLi (2 eq, 5 mol%), THF, rt, 1 h
PMHS (2.5 eq), Cp2TiCl2,
2. Add ester, 2 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
Ph3SiH, (C6F5)3B (1 mol%), MeC6H5, rt
(5 mol%), 40-55°, 6 h
(EtO)3SiH (2.5 eq), Ti(OPr-i)4,
EtMgBr (2 eq), THF, rt, 3 h
PMHS (5 eq), Cp2TiCl2 (15 mol%),
I (71)
I (47)
Br
I (75)
I (53)
Br
OH
OH
CHO
I
+
+
(90)
(88)
(65)
O
H (70)
OH
OEt
(6)
(40)
299
291
290
289
280
116
291
289
276
C8
S
O
O
OEt
OEt
OMe
O
O
Ester
2. Add ester, 24 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
EtMgBr (2 eq), THF, rt, 1.5 h
PMHS (2.5 eq), Cp2TiCl2 (2 mol%),
Ti(OPr-i)4 (5 mol%), 40-55°, 16 h
(EtO)3SiH (2.5 eq), PhSiH3 (1.4 eq),
ester addition, rt, 0.5-2 h
2. (EtO)3SiH (2 eq),
THF, –15°, 15 min
1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),
EtMgBr (2 eq), THF, rt, 17.5 h
PMHS (2.5 eq), Cp2TiCl2 (5 mol%),
ester addition, rt, 0.5-2 h
2. (EtO)3SiH (2 eq),
THF, –15°, 15 min
1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),
65°, 24 h
PMHS (2.5 eq), Ti(OPr-i)4 (25 mol%),
(5 mol%), 40-55°, 22 h
(EtO)3SiH (2.5 eq), Ti(OPr-i)4,
EtMgBr (2 eq), THF, rt, 17.5 h
PMHS (2.5 eq), Cp2TiCl2 (5 mol%),
Conditions
I (52)
I (94)
I (75)
I (92)
I (88)
I (8)
S
O
I
+
I
OH
S
OH
OH
(93)
(93)
(75)
OH
S (20)
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
280
289
291
290
289
290
292
291
289
Refs.
277
N
CO2Et
EtO
O
O
O
OEt
OEt
MeMgCl (1 eq)
Zn(EH)2
Me2N(CH2)2OH (1 eq) H2N(CH2)2NH2 (1 eq) Me2N(CH2)2NMe2 (1 eq)
ZnEt2 ZnEt2 ZnEt2
Cp2TiMe2 (10 mol%), 80°, 39 h
PhMeSiH2 (1.5 eq),
(1.5-3.0 mol%), C6D6, rt, 20 min
PhSiH3 (1.2 eq), Mn(CO)5Br
(1.5-3.0 mol%), C6D6, rt, 30 min
OEt
OEt
N II
I
+
OSi(OEt)PhMe
(84)
(84)
(13)
(13)
(78)
(66)
(62)
(8)
(100)
(2)
(96)
(100)
N
EtO
LiAlH4
ZnCl2
PhSiH3 (1.2 eq), Mn(CO)5Br
AlH(Bu-t)2 (1 eq) LiH
Znl2
I
Zn(EH)2
AlEt3 (2 eq)
NaBH4 (1 eq)
Zn(OAc)2
BH3 (1 eq)
NaBH4 (1 eq)
Zn(O2CC6H5)2
Zn(EH)2
NaBH4 (1eq)
Zn(EH)2
Zn(EH)2
Additive
Zinc catalyst
additive, (i-Pr)2O, 70°, 4 h
PMHS (xs), zinc catalyst (0.2 eq),
I + II (90), I:II = 4:1
(68)
(81)
264
295
295
738
278
C8-14
C8-11
R1
Ar
O
(83) (90) (93) (93)
3-MeC6H4
4-MeC6H4
2,4-Me2C6H3
Temp 23 23 65 65 65 65 70 40 70 40
x 100 100 100 100 25 25 25 100 25 100
R2 Et Et Me Et Me Et Me Me Me Me
Br(CH2)5
I(CH2)5
2-FC6H4
2-BrC6H4
4-MeOC6H4
n-C9H19
CH2=CH(CH2)8
CH C(CH2)8
1-adamantyl
t-BuO2C(CH2)7
OR2
5.5 h
24 h
22 h
24 h
24 h
24 h
1.25 h
2h
24 h
24 h
Time
(94)
3,5-Cl2C6H3
(56)
(>99)
(63)
(78)
(93)
(89)
(87)
(80)
(79)
(87)
OH
(81)
(97)
2,4-Cl2C6H3
3,4,5-(MeO)3C6H2
(96)
4-ClC6H4
OH
(95)
R1
Ar
4-BrC6H4
PMHS (2.5 eq), Ti(OPr-i)4 (x mol%)
THF, rt
PMHS (3 eq), TBAF (2 mol%),
Ph
Ar
OMe
Conditions
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
R1
O
Ester
292
278
Refs.
279
C9
C8-19
Br
R
O
1
10 10 10 10 10 10 5 2 10
(E)-PhCH=CH 4-O2NC6H4 4-HOC6H4 4-MeOC6H4 n-C11H23 n-C17H35 n-C17H35 n-C17H35 n-C17H35
O
O
O
O
O
O
1
10
BnCH2
O2CCF3
1
10
80 h
16 h
16 h
16 h
16 h
16 h
16 h
16 h
5h
16 h
8h
5h
Time
TBAF/alumina (1 mol%), MeC6H5, rt
PMHS (5 eq), Cp2TiF2 (5 mol%),
TBAF/alumina (1 mol%), MeC6H5, rt
Cp2Ti(OC6H4Cl-4)2 (2 mol%),
PMHS (5 eq),
CH2Cl2, rt, 20 h
Et3SiH (6.0 eq), (C6F5)3B (5 mol%),
AlCl3 (0.5 eq), 40°, 2 h
EtCl2SiH (2 eq),
AlBr3 (0.25 eq), 40°, 2 h
EtCl2SiH (2 eq),
0.5
1
0.5
1
1
1
1
1
1
Bn
y
x 10
Ph
THF
PMHS (x eq), Ti(OPr-i)4 (y eq),
OMe R
(87)
(92)
(93)
(98)
(89)
(88)
(81)
(84)
(82)
(65)
(76)
Br
O
OH
O
(69)
+
(>99)
(87)
(88)
OH
OSiEt3
OH
(86)
I I (84)
R
OH
(2)
301, 302
301, 302
282
192
192
279
280
C9
O 2N
Br
R
Bn
O
OEt
O
OEt
OEt
OEt
O
O
O
OEt
OMe
O
Ester
Ti(OPr-i)4 (5 mol%), 40-55°, 20 h
(EtO)3SiH (1.3 eq), PhSiH3 (1.4 eq),
EtMgBr (2 eq), THF, rt, 3 h
PMHS (2.5 eq), Cp2TiCl2 (15 mol%),
ester addition, rt, 0.5-2 h
2. (EtO)3SiH (3.3 eq),
THF, –15°, 15 min
1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),
CsF (1 eq), 60°, 30 min
(88)
+
R
O2N
Br
R
OH
OH
(75)
(40)
NH2
OH
(88) (81)
OH
(9)
291
289
290
83
82, 83
I (90)
OH
(81)
278
(EtO)3SiH (2.3 eq),
OH
(76)
289
288
I
OH
(88)
Refs.
I (86)
Bn
OH
Product(s) and Yield(s) (%)
[HSi(OEt)4]K, THF, rt, 8-15 h
DMSO, 80°, 6.5 h
PMHS (1.2 eq), KF•2H2O (1.3 eq),
PMHS (3 eq), TBAF (2 mol%), THF, rt
EtMgBr (2 eq), THF, rt, 5 h
PMHS (2.5 eq), Cp2TiCl2 (5 mol%),
Conditions
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
281
N
AcO
Ar
Ph
Ph
Ph
Ph
N
O
+
CO2Et
OEt
O
OMe
OMe
OMe
OMe
OMe
CO2Et
O
OH
O
OH
O
O
OH
Ph
O OMe
C6D6, rt, 12 h
Mn(CO)4PPh3Ac (3.0 mol%),
PhSiH3 (1.2 eq),
TMSOTf (3.1 eq), CH2Cl2, rt, 20 h
Et3SiH (5.0 eq), TiCl4 (1.5 eq),
C6D6, rt, 30 min
Mn(CO)4PPh3Ac (3.0 mol%),
PhSiH3 (1.2 eq),
Cp2TiMe2 (10 mol%), 6 d
PhMeSiH2 (1.5 eq),
Cp2TiMe2 (10 mol%), rt, 24 h
PhMeSiH2 (1.5 eq),
(1.5-3.0 mol%), C6D6, rt, 25 min
PhSiH3 (1.2 eq), Mn(CO)5Br
THF, 65°, 9.5 h
(MeO)3SiH (3.5 eq), LiOMe (6 mol%),
THF, 65°, 9.5 h
(MeO)3SiH (3.5 eq), LiOMe (6 mol%),
THF, rt
PMHS (3 eq), TBAF (2 mol%),
EtO
Ar
Ph
N I
N
I
OH
I (78)
Ph
Ph
OH
+
Ph
(70)
OH
(94)
OMe
OMe
(40) (72)
(12)
N
(20)
I + II (100), I:II = 3:2
4-O2NC6H4
N II
(80)
+
+
4-BrC6H4
Ph
Ar
(83)
OSi(OEt)PhMe
(80)
(—)
(90) >95% ee
OSi(OEt)PhMe
OEt
OH
OH
295
297
295
264
264
295
294
294
278
282
C9-15
C9-10
C9
R
1
X
OEt
2
SEt
SEt
O
OMe
OEt
OR
O
O
O
O
PhS
Ph
Ph
Ph
O
O
O
OEt
Ester
PPh3 (5 eq), THF, rt
Ph2SiH2 (3 eq), catalyst (1.25 mol%),
Ph3SiH (1 eq), (C6F5)3B (2 mol%)
acetone, rt, 30-60 min
Et3SiH (2-3 eq), Pd/C (2-5 mol%),
acetone, rt, 30-60 min
Et3SiH (2-3 eq), Pd/C (2-5 mol%),
MeC6H5, rt
Ph3SiH, (C6F5)3B (2 mol%),
EtI, Et2NH, MeC6H5, 100°, 16 h
Et3SiH (1.5 eq), [RuCl2(CO)3]2,
MeC6H5, rt
Ph3SiH, (C6F5)3B (2 mol%),
Conditions
R1
X
PhS
Ph
Ph
Ph
H
H
H
OH
O
O
O
CHO
O
OEt
OSiPh3
(75)
(91)
X = Me, Cl, NO2 (—)
X = H (80)
(78)b
(80)c
(65)
OEt
OSiPh3
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
293
115
300
300
116
299
116
Refs.
283
C10
72 h 6h 72 h
[RhCl(cod)]2 RhCl(PPh3)3 [RhCl(cod)]2
i-Pr i-Pr O O
n-C11H23
n-C11H23
F
6h
RhCl(PPh3)3
i-Bu
n-C9H19
MeO
O
F
72 h
[RhCl(cod)]2
i-Bu
n-C9H19
O
O
O2CCF3
CH2CN
N
OAc
O
OBu-t
O
(94)
72 h
[RhCl(cod)]2
Et
n-C9H19
ester addition, –20° to rt, 8 h
2. (EtO)3SiH (2 eq),
THF, –15°, 15 min
1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),
TFA (13 eq), rt, 1 h
Et3SiH (1.2 eq),
MeC6H5, rt
TBAF/alumina (1 mol%),
PMHS (5 eq), Cp2TiF2 (2 mol%),
TBAF/alumina (1 mol%), MeC6H5, rt
Cp2Ti(OC6H4Cl-4)2 (2 mol%),
PMHS (5 eq),
Ph3SiH, O2NC6H5, 80°, 13 h
(92)
72 h
[RhCl(cod)]2
n-C10H21
Me
O2CCF3
(92)
72 h
[RhCl(cod)]2
Et
Bn
n-C7H15
(92)
24 h
RhCl(PPh3)3
Et
Br(CH2)6
HO
O
I (97) OAc
I
CH2CN
N
(63)
(80)
(66)
(95)
(92)
(98)
(56)
72 h
[RhCl(cod)]2
Et
Br(CH2)6
(70)
24 h
RhCl(PPh3)3
Et
Ph
Time 144 h
[RhCl(cod)]2
Et
Ph
Catalyst
R2
R1
O
O
(90)
OBu-t
(81)
OH
(87)
(96)
290
739
301
301, 302
193
284
C11
C10-11
C10
Bn
O
O
O
OMe
OMe
O2CCF3
O OAc
OMe
CO2Me
O
OMe
O
OEt
O
O
CH2CO2Me
N
OMe
N Boc
Ar
Ph
Ph
Ph
Ph
Ester
TBAF/alumina (1 mol%), MeC6H5, rt
PMHS (5 eq), Cp2TiF2 (2 mol%),
TBAF/alumina (1 mol%), MeC6H5, rt
Cp2Ti(OC6H4Cl-4)2 (2 mol%),
PMHS (5 eq),
Et3SiH (1.2 eq), TFA (13 eq), rt, 1 h
EtMgBr (2 eq), THF, rt, 23 h
PMHS (2.5 eq), Cp2TiCl2 (5 mol%),
TMSOTf (3.1 eq), CH2Cl2, rt, 20 h
Et3SiH (5.0 eq), TiCl4 (1.5 eq),
THF, rt
PMHS (3 eq), TBAF (2 mol%),
THF, 65°, 9.5 h
(MeO)3SiH (3.5 eq), LiOMe (6 mol%),
2. Add ester, 0.5 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (2.4 eq), 223 (1 mol%),
40-55°, 10 h
Ti(OPr-i)4, (5 mol%),
(EtO)3SiH (2.5-3.0 eq),
Conditions
I (87)
OAc
OH
OMe
OH
OH
OH
OH
O I
OH
CH2CO2Me
N
OMe
N Boc
Bn
O
Ar
Ph
Ph
Ph
Ph
(93)
(80)
(70)
4-MeOC6H4
Ph
Ar
(84)
(76)
(97)
(89)
(89)
(75)
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
301
301, 302
739
289
297
278
294
280
291
Refs.
285
Ph
O
CO2Me
O
OEt
O OMe
2. Add ester, 1 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (2.4 eq), 2 (1 mol%),
EtMgBr (2 eq), THF, rt, 23 h
PMHS (2.5 eq), Cp2TiCl2 (5 mol%),
ester addition, –20° to rt, 8 h
2. (EtO)3SiH (1.2 eq),
THF, –15˚, 15 min
1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),
Ti(OPr-i)4 (100 mol%), 65°, 8 h
PMHS (2.5 eq),
EtMgBr (2 eq), THF, –78° to rt, 1.5 h
PMHS (2.5 eq), Cp2TiCl2 (5 mol%),
I (55)
I (94)
Ph I
O
+
OH
Ph
OH
OH
(44)
II
+
OEt
(82)
(58)
HO
(11)
OH
(28)
280
289
290
292
289
286
C11
Ph
O OEt
Ester
1h
10°
1,4-dioxane
EtMe2Si
2. Add ester
I (56)
22 h
20°
C5H5N
EtMe2Si
1. EtMe2SiH (2.4 eq), 224 (1 mol%)
8h
20°
oxepane
EtMe2Si
1h
20°
C6H6
EtMe2Si 2h
24 h
20°
1,4-dioxane
(i-Pr)3Si 2h
21 h
20°
1,4-dioxane
Et3Si
20°
21 h
20°
1,4-dioxane
Ph2MeSi
20°
21 h
20°
1,4-dioxane
PhMe2Si
Et2O
5h
20°
1,4-dioxane
tetrahydropyran
2h
20°
1,4-dioxane
HMe2Si(CH2)2(Me)2Si Et2MeSi
EtMe2Si
1h
20°
EtMe2Si
Time
Temp
Ph
1,4-dioxane
+
OEt
Solvent
I
EtMe2Si
Ph
R3Si
2. Add ester
1. R3SiH (2.4 eq), 223 (1 mol%), solvent
Conditions
III
(100)
(0)
(69)
(94)
(100)
(100)
(0)
(7)
(74)
(95)
(100)
(100)
(100)
H
28:0:72
0:0:0
61:0:39
53:0:47
45:16:39
42:0:58
0:0:0
0:100:0
16:0:84
17:0:83
76:0:24
16:0:84
20:0:80
I:II:III
II OSiR3
Ph
% Conversion
+
O
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
280
280
Refs.
287
Ph
Ph
OH
O
O OMe
OEt
1.5 TMSOTf TMSOTf
— 1.5 AgOTf 1.5 AgOTf, TMSCl 3.0, 3.0
5.0 5.0 5.0
z
3.0
3.0
3.0
—
5.0
Co-catalyst
y 3.0 None
x 5.0
co-catalyst (z eq), CH2Cl2, rt, 20 h
Et3SiH (x eq), TiCl4 (y eq),
THF, 65°, 0.5 h
(MeO)3SiH (3.0 eq), LiOMe (6 mol%),
2. Add ester, 1 h
THP, 20°, 0.5 h
1. Et2MeSiH (2.4 eq), 223 (1 mol%),
2. Add ester
1. EtMe2SiH (2.4 eq), 226 (1 mol%)
2. Add ester
1. EtMe2SiH (2.4 eq), 225 (1 mol%)
+
Ph
Ph
(76)
(63)
(—)
(81)
(27)
OH
I (87)
I (40) +
I (34)
(92)
OMe
OH
II (0.8)
II (0.3)
297
294
280
280
280
288
C12
C11-16
C11
Ph
O
O
O
CO2R
O2CCF3
O
O
n-C6H13
Ph
O
n-C7H15
Ester
Ph2SiH2, O2NC6H5, 80°, 7 h
TMSOTf (3.1 eq), CH2Cl2, rt, 20 h
Et3SiH (5.0 eq), TiCl4 (1.5 eq),
TMSOTf (3.1 eq), CH2Cl2, rt, 20 h
Et3SiH (5.0 eq), TiCl4 (1.5 eq),
2. Add ester, 2 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
2. Add ester, 3 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
Conditions
Ph
O
n-C6H13
n-C7H15
Ph
O
O
(90)
OR
(67)
(39) (79)
i-Pr n-Bu Ph
(67)
c-C6H11 (34)
(78)
(81) Et
Me
R
(73)
(79)
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
193
297
297
280
280
Refs.
289
O
n-C9H19
8
O
O
OMe
OEt
2.5 1.0 2.5 2.5 2.5 1.0 1.0
4 4 4 3 2 3 3 3 24 h
6h
6h
72 h
72 h
72 h
72 h
72 h
Time
23 65 65 23 65 65 23
25 25 100 25 100 100
Ti(OPr-i)4 Ti(OPr-i)4 Ti(OPr-i)4 Ti(OPr-i)4 Ti(OBu-n)4 Ti(OBu-n)4 THEATi(OPr-i)
PMHS PMHS Ph2SiH2 Cl3SiH PMHS PMHS Ph2SiH2
ester addition, –20° to rt, 8 h
2. (EtO)3SiH (2 eq),
n-BuLi (10 mol%), THF, –15°, 15 min
1. (EBTHI)2TiCl2 (5 mol%),
65°, 2.5 h
I (67)
O
65
25 100
Ti(OPr-i)4
PMHS
PMHS (2.5 eq), Ti(OPr-i)4 (100 mol%),
Temp
x
Catalyst
I
n-C9H19
Silane
Silane (2.5 eq), catalyst (x mol%)
y 5.0
x
PPh3 (2y eq), THF, rt
Ph2SiH2 (x eq), [Rh(cod)]2 (y mol%),
I
OH
8
OH
96 h
2h
24 h
24 h
25 h
2h
25 h
24 h
Time
(56)
(51)
(96)
(72)
(98)
(40)
(92)
(96)
I
(81)
(0)
(90)
(75)
(0)
(100)
(100)
(100)
(100)
290
292
292
293
290
C12
BnO
O
O
6
6
6
O
O
OEt
6
OMe
OMe
OEt
O
O
O
OMe
OEt
Ester
PMHS (10 eq), Ti(OPr-i)4 (1 eq), THF
EtMgBr (2 eq), THF, rt, 1 h
PMHS (2.5 eq), Cp2TiCl2 (5 mol%),
ester addition, –20° to rt, 8 h
2. (EtO)3SiH (2 eq),
THF, –15°, 15 min
n-BuLi (10 mol%),
1. (EBTHI)2TiCl2 (5 mol%),
Ti(OPr-i)4 (5 mol%), 40-55°, 22 h
(EtO)3SiH (2.5 eq), PhSiH3 (1.4 eq),
Ti(OPr-i)4 (5 mol%), 40-55°, 18 h
(EtO)3SiH (2.5-3.0 eq),
Ti(OPr-i)4 (5 mol%), 40-55°, 21 h
(EtO)3SiH (2.5-3.0 eq),
THF, rt
PMHS (3 eq), TBAF (2 mol%),
Ti(OPr-i)4 (5 mol%), 40-55°, 16 h
(EtO)3SiH (2.5-3.0 eq),
MeC6H5, rt
Ph3SiH, (C6F5)3B (1 mol%),
Ti(OPr-i)4 (5 mol%), 40-55°, 10 h
(EtO)3SiH (2.5-3.0 eq),
Conditions
BnO
I (91)
I (83)
O
I (95)
I (69)
6
6
6
OH
I
I
I
6
(95)
(89)
OH
OH
OH
OH
OH
(80)
(70)
(83)
(87)
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
279
289
290
291
291
291
278
291
116
291
Refs.
291
HO
Ph
PhO
Ph
8
9
O
O
O
OAc
O
O
9
O
O
OEt
OMe
SEt
O
OMe
OMe
SEt
Ti(OPr-i)4 (5 mol%), 40-55°, 10 h
(EtO)3SiH (2.5-3.0 eq),
[HSi(OEt)4]K, THF, rt, 8-15 h
PMHS, KF•2H2O, DMSO, 80°, 6 h
(EtO)3SiH, CsF, 60°, 0.5 h
acetone, rt, 30-60 min
Et3SiH (2-3 eq), Pd/C (2-5 mol%),
acetone, rt, 30-60 min
Et3SiH (2-3 eq), Pd/C (2-5 mol%),
TMSOTf (3.1 eq), CH2Cl2, rt, 20 h
Et3SiH (5.0 eq), TiCl4 (1.5 eq),
CH2Cl2, rt, 20 h
Et3SiH (3.3 eq), (C6F5)3B (5 mol%),
9
HO
8
O
O
OAc
O
I (70)
Ph
PhO
Ph
9
I
OH
H
H
O
(84)
(65)
(88)
(94)
(92)
(70)
H
OH
(40)
CH2OSiEt3
291
288
83
83
300
300
297
282
292
R1
6
OEt
SEt
OMe
OBu-t
O
OR2
CO2Me
O
O
O
i-Pr i-Pr Si H O O
H
BocHN
n-C11H23
Ph
C13-16
C13
Ester
TBAF (0.5 eq), CH2Cl2, rt, 15 min
MeOH, rt
2. Camphorsulfonic acid (0.1 eq),
acetone, rt, 30-60 min
1. Et3SiH (2-3 eq), Pd/C (2-5 mol%),
2. Add ester, 3 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
2. Add ester, 12 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
ester addition, –20° to rt, 8 h
2. (EtO)3SiH (2 eq),
THF, –15°, 15 min
n-BuLi (10 mol%),
1. (EBTHI)2TiCl2 (5 mol%),
DMSO, 80°, 6 h
PMHS (2.3 eq), KF•2H2O (1 eq),
CsF (1 eq), 60°, 30 min
(EtO)3SiH (2.3 eq),
Conditions
R1
O
i-Pr
H
Si
BocHN
n-C11H23
Ph
I (62)
I (70)
OH
OH
O OR2
CO2Me
(70)
(95)
OMe
Me Me Et Me Me
n-Pr n-Pr n-Bu Ph
(97) (95) (98) (98) (96)
1:1 2:1 1:1 1:1 2:1
R2 cis:trans n-Pr
R1
Ph
+ n-C11H23
(80) +
(69)
OH
OMe
OMe
Pr-i
I
6
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
(17)
OBu-t (7)
303
300
280
280
290
83
83
Refs.
293
C15
C14-15
C14
PhO
PhO
Ph
O
O
O
N H
N H
CO2H
CO2Bu-t
OMe
NH2 CO2Bu-t
O
CO2H
CO2Bu-t
CO2R
OEt
CO2Bu-t
N H
CO2Me
HN
n-C11H23
O
O
HO
t-BuO
n-Bu
i-Pr i-Pr Si H O O
CH2Cl2, rt, 35 min
Et3SiH (2.5 eq), TFA,
CH2Cl2, rt, 45 min
Et3SiH (2.5 eq), TFA,
TMSOTf (3.1 eq), CH2Cl2, rt, 20 h
Et3SiH (5.0 eq), TiCl4 (1.5 eq),
2. Add ester, 22 h
THP, 20°, 0.5 h
1. Et2MeSiH (4 eq), 223 (1 mol%),
Et3SiH (xs), TFA, 18°, 18 h; 45°, 3 h
CH2Cl2, rt, 65 min
Et3SiH (2.5 eq), TFA,
TBAF (0.5 eq), AcOEt, rt, 15 min
H2N
PhO
Ph
O
+
(65)
(72)
(100) + Me3CH (—)
t-Bu
i-Pr
R
OEt
Me3CH (—)
(98) + Me3CH (—)
OR
CO2H
NH2 CO2H
O
N H
(96)
(81)
(17) + n-C11H23
CO2H
OH
(87)
OMe CO2H
O
P r-i
CO2H
Si
CO2Me
n-C11H23
O
HN
H2N
n-Bu
O
i-Pr
(75)
307
307
297
280
714
307
303
294
C17
C16
C15
PhO
EtS
BnO
N H
t-BuO
O
N H
O
SMe
OBn
O
O
O
EtS
CO2Bu-t
OMe
O
O
O
O
O
O
Ester
O
MeC6H5, rt
TBAF/alumina (1 mol%),
Cp2Ti(OC6H4Cl-4)2 (3 mol%),
PMHS (5 eq),
Et3SiH, TFA, CH2Cl2
acetone, rt, 30-60 min
Et3SiH (2-3 eq), Pd/C (2-5 mol%),
CH2Cl2, rt, 25 min
Et3SiH (2.5 eq), TFA,
Et3SiH, Pd/C
MeC6H5, rt
(2 mol%), TBAF/alumina (1 mol%),
PMHS (5 eq), Cp2Ti(OC6H4Cl-4)2
Conditions
H2N
H
O
BnO
O
O
CO2H
N H
OBn
OH
O
OH
O
SMe
OMe
HO
O
O
O
(94)
H
(97)
(100) + Me3CH (—)
O
(95) + Me3CH (—)
(—)
(91)
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
302
741
300
307
740
302
Refs.
295
C17-18
MeO
R1
AcO
Ph
O
R3
O
O
SEt
R4
CO2Bu-t
R4
CO2H
H (88)
(88)
R2
(100)
MeO H
MeO
MeO
24 h
H H
R3
24 h
18 h
MeO H
R2
H
O
H
O
Me3CH (—)
+
R4 MeO MeO MeO
H MeO MeO
—OCH2O—
R3
Me3CH (—)
Me3CH (—)
24 h
N
Cbz
O
CO2H
+
+
R1
MeO
R1
AcO
Ph
TBSO
(90)
(100)
CO2H
Time
Et3SiH (3 eq), TFA (5 eq)
acetone, rt, 30-60 min
Et3SiH (2-3 eq), Pd/C (2-5 mol%),
acetone, rt, 30-60 min
Et3SiH (2-3 eq), Pd/C (2-5 mol%),
CH2Cl2, rt, 15 min
H2N
H N
Et3SiH (2.5 eq), TFA,
CO2H
OBz
SBu-t
H2N
N
O
H N
CH2Cl2, rt, 45 min
Et3SiH (2.5 eq), TFA,
CH2Cl2, rt, 25 min
Et3SiH (2.5 eq), TFA,
PhO
SBu-t
CO2Bu-t
OBz
CO2Bu-t
SEt
O
H
R2
Cbz
N
O
TBSO
O
N H
N H
O
N
O
t-BuO
PhO
PhO
(85)
(54)
(80)
(63)
305
300
300
307
307
307
296
C18
C17-19
n-C16H33
O
O
N H
R4
N H
R3
O
t-BuO
PhO
R2
R1
MeO
H
R6
MeO MeO MeO MeO MeO
MeO MeO MeO MeO MeO
O
(73)
(78)
(81)
(73)
(82)
(80)
(83)
(87)
R5
O CO2Bu-t
H2N
CH2Cl2, rt, 20 h
Et3SiH (4.0 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 90 min
n-C17H36
O (96)
H N
Et3SiH (2.5 eq), TFA,
SBu-t
H N
CO2Bu-t SBu-t
CH2Cl2, rt, 45 min
SMe H2N
5h
5h
4h
6h
3h
2h
3h
3h
Time
R4
R3 R6
CO2H
(100)
(100)
+
+
Me3CH (—)
Me3CH (—)
Product(s) and Yield(s) (%)
CO2H
CO2H
H N
MeO
MeO
H
MeO
H
H
MeO
H
H H
H —OCH2O—
R5 MeO
R4
Et3SiH (2.5 eq), TFA,
MeO
H
MeO
MeO
H MeO
MeO
MeO
MeO
MeO
H
H
H
MeO
MeO
H
R3
H
MeO
MeO
—OCH2O—
R2 MeO
R1
R2
R
1
SMe
R6
Et3SiH (3 eq), TiCl4, CH2Cl2, 0°
Conditions
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
H N
R5
OMe
O
O
O
Ester
282
307
307
305
Refs.
297
C19
O
O
7
H
CO2Me
7
O
OMe
CO2Me
O
O
OMe 1-Np
n-C17H35
O
CO2Me
N SO2Ph
OMe
O
SEt
CO2Me
n-BuLi (2 eq), THF, rt, 1.5 h
PMHS (2.5 eq), Cp2TiCl2 (2 mol%),
65°, 24 h
PMHS (2.5 eq), Ti(OPr-i)4 (100 mol%),
PMHS (10 eq), Ti(OPr-i)4 (1 eq), THF
Et3SiH (xs), TFA
2. Add ester, 6 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
CH2Cl2, rt, 20 h
Et3SiH (6 eq), (C6F5)3B (5 mol%),
acetone, rt, 30-60 min
Et3SiH (2-3 eq), Pd/C (2-5 mol%),
TMSOTf (3.1 eq), CH2Cl2, rt, 20 h
Et3SiH (5.0 eq), TiCl4 (1.5 eq),
I (82)
7
H
OMe
n-C17H33
OH
OH
7
Np-1
(78)
(32)
O
OH
(98)
OH
CO2H
I
O
n-C18H38
O
CO2Me
N SO2Ph
H
n-C17H33
(92)
(89)
(90)
+
(43)
OMe
OMe
(22)
289
292
279
304
280
281
300
297
298
C21
C20
C19
BnO
O
7
O
N H
O
n-C17H33
7
7
O CO2Bu-t
BnC(O)NH
7
CH2Cl2, rt, 40 min
O
7
7
O
7
OH
H N
Et3SiH (2.5 eq), TFA,
CH2Cl2, rt, 20 min
Et3SiH (2.5 eq), TFA,
I
O
n-C17H33
I (64)
7
7
SBu-t
N H
CO2Bu-t
ester addition, –20° to rt, 8 h
2. (EtO)3SiH (2 eq),
THF, –15°, 15 min
n-BuLi (10 mol%),
1. (EBTHI)2TiCl2 (5 mol%),
2. Add ester, 6 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (4 eq), 223 (1 mol%),
THF, rt, 1 h
(EBTHI)TiCl2 (5 mol%), n-BuLi (2 eq),
PMHS (2.5 eq),
65°, 5 h
PMHS (2.5 eq), Ti(OPr-i)4 (100 mol%),
Ti(OPr-i)4 (5 mol%), 40 to 55°, 10 h
(EtO)3SiH (2.5-3.0 eq),
H N
O
OEt
OMe
OMe
Conditions
N H
OMe
(85) + Me3CH (—)
n-C17H33
(78) + Me3CH (—)
CO2H
CO2H
O
OH
(90)
(85)
(92)
(32) +
OH
OH
Product(s) and Yield(s) (%)
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
SBu-t
O
7
O
OMe
7
O
7
O
Ester
(22)
307
307
290
280
289
292
291
Refs.
299
C26
C25
C22
C21
O
O
MeO
BnO
N H
N H
Boc
N
DMTSO
O
BnO
O
8
O
H
HN
O
H N
CO2Bu-t
Ph
NH2
CO2Bu-t
OBz
Ph
O
O
O
SEt
SEt
OBn
2
O
Et3SiH (2.5 eq), TFA, CH2Cl2, rt, 35 min
3. TBAF, AcOH, MeOH
2. Camphorsulfonic acid (0.1 eq), MeOH
CH2Cl2, rt, 40 min
1. Et3SiH (5 eq), Pd/C (15 mol%),
MeC6H5, rt
TBAF/alumina (1 mol%),
Cp2Ti(OC6H4Cl-4)2 (5 mol%),
PMHS (5 eq),
CH2Cl2, rt, 30 min
Et3SiH (2.5 eq), TFA,
CsF (1 eq), 60°, 9 h
(EtO)3SiH (1.1 eq),
BnO
O
MeO
DMTSO
HO
BnO
O
N H
O
N
Boc
N H
8
N
HN
O MeO
N
CO2H
Ph
Ph
(98)
O
+
OBn
H
H
(92)
(75)
CO2H
OBz
OH
(83) + Me3CH (—)
(65)
Me3CH (—)
307
300
302
307
79
300
C28
C27
H
O
H N
O
OAc
NH
7
N H SBu-t
O
OBn
O
CO2Bu-t
CO2Bu-t
CH2Cl2, rt, 95 min
Et3SiH (2.5 eq), TFA,
–20°, 24 h
Et3SiH (1.5 eq), BF3•OEt2 (1.1 eq),
(EtO)3SiH, CsF, rt, 72 h
BnMe2SiH, TFA, rt, 20 h
CH2Cl2, rt, 75 min
Et3SiH (2.5 eq), TFA,
Conditions
H2N
O H
n-C8H17
n-C8H17
H2N
H N
O
I
NH
H N
N H SBu-t
O
N H
OBn
CO2H
(100)
(65)
(80)
n-C8H17
OH
SBu-t
O
7
+
Me3CH
(CH2)7CO2Me
+
II
SPh
(—)
Me3CH (—)
I + II (62)
CO2Bu-t (100) +
Product(s) and Yield(s) (%)
(CH2)7CO2Me
OAc
OAc
SPh
O
Ph
TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)
(CH2)7CO2Me
SPh
OAc
O
H N
n-C8H17
OAc
N H SBu-t
O
(CH2)7CO2Me
OAc
SPh
t-BuO2NH
O
AcO
n-C8H17
+
n-C8H17
BOCNH
Ph
Ester
307
510
83
742
307
Refs.
301
C39
C36
C35
C33
C29
BnO
The yield was determined by NMR spectroscopy.
No reduction occurred in this reaction.
The product was isolated as the phenylhydrazone.
c
TBAF (10 mol%), 0°
TBAF (10 mol%), 0°
b
CO2Et
SiMes2H
CO2Et
SiMes2H
TBAF (10 mol%), 0°
TBAF (10 mol%), 0°
TBAF (10 mol%), 0°
a
Ph
BnO
BnO
CO2Et
SiMes2H
CO2Et
SiMes2H
O
Et
TBSO
Et
O
CO2Et
SiMes2H
BnO
Mes Si O
Mes Si O
O
O
Mes Si O
Mes
Mes
BnO
Mes
Mes2Si
BnO Ph
O Et
TBSO
Et
O
Mes2Si
OEt
OEt
OEt
OEt
OEt
(79) dr = 93:7
(82) dr = 85:15
(—) dr = 96:4
(—) dr = 96:4
(91) dr = 98:2
743
743
743
743
743
302
C4-7
C3
C2-7
C2-7
C2
R
Et
R
R
H
H
H
O
H
H R = n-Pr, Ph
O
4-ClC6H4, 4-MeC6H4, 4-NCC6H4
R = Me, Et, i-Pr, t-Bu, Ph,
O
O
O
Aldehyde
ClRh(PPh3)3 (5x10-4 M)
Ph(Np-1)2SiH2,
CH2Cl2, 0°, 2 h
Et3SiH, TMSOTf, c-C6H11OTMS3,
CH2Cl2, rt, 2 h
Et3SiH (2 eq), TMSOTf (0.1 eq),
Et3SiH, HClO4, MeCN, rt
PhCONH2, solvent, 18 h
Et3SiH (3 eq), TFA (2.9 eq),
–78° to rt, 5-6 h
1-AdOTMS (1.25 eq), n-C5H12,
Me3SiH (1.25 eq), TMSI (0.3 eq),
Conditions
R
Et
Et
R
Ph
N H
C6H11-c
Et
(—)
R
H
OSiHPhNp-1
O
O
OH
O
OEt
(—)
(100)a
(100)a
120°
MeC6H5
c-C6H11
22° 120°
MeC6H5
MeCN
Me t-Bu
Temp
Solvent
R
(69)
Product(s) and Yield(s) (%)
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES
(92)
(90)
(95)
744
334
334
380
326
338
Refs.
303
C5
C4-7
C4-9
C4
R
R1
2h
0°
Et3SiH, TMSI, n-C8H17OTMS, CH2Cl2
2-octyl Bn Bn
Ph
n-C7H15
4-MeO2CC6H4
S O
Ph
Ph
H
Bn
Ph
2h
1h
98:2 >98:2
HMPA, rt, 2.5 h
Ph2SiH2 (1.1 eq), TBAF (5 eq),
18-C-6 (0.05 eq), CH2Cl2, rt, 11 h
PhMe2SiH (1.1 eq), CsF (0.1 eq),
0°, 4-6 h
S
99:1 85:15
(65)
>98:2
OH
88:12
(64)
75:25
n-C5H11
R
68:32
(64)
74:26
(87) (72) (80)
(E)-PhCH=CH PhC C H2C=CH(CH2)8
OSiMe2Ph
(62)
(64)
(98) BnCH2
OSiMe2Ph
(98) (100)
(95)
4-ClC6H4 4-MeOC6H4
(98)
Ph 4-O2NC6H4
(99)
(81)
Ar
OH
2-C4H3S
2-C4H3O
R
I:II 91:9
R
OH
(73)
I
+
I + II
Ar
OH
Z:E
R
OH
>98:2
Cl3SiH (1.5 eq), CH2Cl2/DMF (4:1),
Ph
O
R
R THF, –78°, 3.5 h
2-C4H3O
H
OSiMe2H , TBAF (6 mol%),
Ar
n-C5H11
R
Ar
O II
320
347
318
400
306
C7
C6
18-C-6 (0.5 mol%), CH2Cl2, rt
PhMe2SiH (1.1 eq), CsF (10 mol%),
18-C-6 (5 mol%), CH2Cl2, rt, 0.5 h
PhMe2SiH (1.1 eq), CsF (10 mol%),
H
2. H3O+
KO2CH (1 eq), DMF, 45°, 19 h
1. Cyclohexanone, Me(EtO)2SiH (1.2 eq),
KF (1 eq), DMF, 10°, 1.75 h
Me(EtO)2SiH (1.5 eq),
(85)
II (72) +
I
II (97)
Et3SiH (1.25 eq), H2SO4, H2O (11 eq), 28°, 1.25 h
II (100)
n-C6H13
I (50)
n-C6H13
Et3SiH (1.1 eq), HCl, 28°, 3 h
(EtO)3SiH (1.1 eq), KF (1 eq), rt, 4 h
Ph2SiH2 (0.5 eq), CsF, rt, 3 min
Ph2SiH2 (0.5 eq), KF, 100°, 6 h
100°, 24 h
Ph2SiH2 (0.5 eq), 1,2-C6H4(CO2K)2,
(60)
(54)
4h
4-pyridinyl O
(67)
9h 20 h
2
OH
SiPh2
(70)
(100)
(60)
c-C6H10O (recovered)
O
OSiPh2H
II
I
(58)
Product(s) and Yield(s) (%)
OSiMe2Ph
OSiMe2Ph
3-pyridinyl
Ar
O
2-pyridinyl
Time
O
H
Conditions
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)
Ar
H
n-C6H13
Ar
O
O
Aldehyde
82
83
313
313
79, 83
83, 319
319
319
345
346, 347
Refs.
307
+
Bn
O Bn
III (92) III (48) III (96) III (90)
PhMe2SiH, EG acid, CH2Cl2, rt, Et3SiH, ZnCl2 (HMe2Si)2O, TMSCl, C6H6, rt, 30 min (HMe2Si)2O, TMSCl, NaI,
t-BuOTMS (1.25 eq)
n-C5H12, –78° to rt, 5-6 h,
TMSH (1.25 eq), TMSI (0.3 eq),
(EtO)3SiH (2.3 eq), KF (1 eq), rt, 20 h
EtOTMS ( 1 eq), CH2Cl2, 0-15°; rt, 2 h
TMSH (1.1 eq), TMSI (5 mol%),
PhMe2SiH, EG acid
Et3SiH, TFA, BnOH, rt, 1 h
O
OEt
n-C6H13
OBu-t
O
n-C6H13
n-C6H13
OBn
III
n-C6H13
III (90)
TMSH, TMSI, TMSOEt, CH2Cl2, 0°, 2 h
III (87)
Et3SiH, H2SO4, MeOH, rt, 1 h
C6H6, rt, 30 min
III (90)
n-C6H13
Et3SiH, TFA, rt, 45 min
TMSOTf (cat.), C6H6, 80°, 30 min
HMe2SiOSiMe2H (1.0 eq),
(63)
OH (100)
(90)
Ph
(49)
C6H13-n
+ Ph
(82)
(96)
O Ph
(0)
338
83
334
333
328
334
328
314
330
330
333
313
314
308
C7
H
O
c-C6H11
H
O
O
O
CO2Et
H
H
OTMS
Aldehyde
OBn , Et3SiH (1 eq),
OBn , Et3SiH (1 eq),
Et3SiH (3 eq), TFA
5-Chloro-N-benzhydrylindole,
MeC6H5
R3SiH (x eq), (Ph3P)CuH (3 mol%),
OTMS TMSOTf (0.1 eq), CH2Cl2, –30°
MeO
O
OTMS TMSOTf (0.1 eq), CH2Cl2, –30°
BnO
n-C5H12, –78° to rt, 5-6 h
TMSH (1.25 eq), TMSI (0.3 eq),
t-BuOTMS (1.25 eq),
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1. TrSbCl6 (5-30 mol%),
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1. SbCl5, TMSCl, SnI2,
Conditions
Cl
MeO
BnO
O
O
Ph
O
c-C6H11
c-C6H11
I (91)
O I
OBn
(84)
Ph
(36)
(84)
x
CO2Et
—
2h
Time
(79)
Ph2MeSi 2.5
PhMe2Si 1.3
R3Si
C6H11-c
OSiR3
N
OBn
(92)
C6H11-c
OBu-t
OH
(89)
Product(s) and Yield(s) (%)
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)
(98)
(95)
355
317
341
341
338
367
306
306
Refs.
309
Ph
O H
II (90)
Me(EtO)2SiH (2.3 eq), KF (1 eq),
Bn
Ph
II (90)
35° rt 80° 80°
DMSO DMF DMF
KF•2H2O KO2CH KO2CH
PMHS Me(EtO)2SiH
PMHS
20°
KF•2H2O
PMHS
DMF
KF
Me(EtO)2SiH
DMF
Salt
Silane
Temp
II
Silane, salt, solvent Solvent
II (90)
Me(EtO)2SiH, KF, 20°, 0.25 h
DMF, 20°, 0.25 h
OH
OSiEt3
O I
11 h
4h
1h
1h
0.25 h
Time
III
Ph
PhMe (84)
(EtO)3SiH (2.3 eq), KF (1 eq), rt, 6 h
MeC6H5, reflux, 1 h
PMHS, TMSOTf (cat.),
PMHS, TMSOTf (cat.), C6H6, reflux, 2 h
PMHS, Pd/C, EtOH, 80°
EtOH, reflux
[Bu2(AcO)Sn]2O (2 mol%),
PMHS (10% xs), II
Ph
Et3SiH (1 eq),
Ph
I (59)
(EtO)3SiH (1.1 eq), CaO, rt, 0.3 h
(Ph3P)3RhCl (0.1 mol%), rt, 5 min
I (72)
Ph
(EtO)3SiH (1.1 eq), HAp, rt, 0.3 h
Et3SiH (1.1 eq), Fe-mont, rt, 0.3 h
(75)
(64)
(67)
(76)
(90)
Bn
(92)
+
(80)
(95)
(100)
Ph
IV
III + IV (95)
82
83
83
83
314
314
316
316
411
353
353
353
310
C7
Ph
O H
Aldehyde
367
II (68)
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
I (92)
Et3SiO(EtHSiO)nSiEt3 (0.5 mol%),
CH2Cl2, rt, 2 h
Et3SiH (2 eq), TMSOTf (0.1 eq),
I (major)
I (80)
Et3SiH, TFA, 30-40°
TFA (8 eq), CHCl3, 50°, 1 h
I (75)
Et3SiH (1.1 eq), BF3•OEt2 (2.0 eq), rt
II (minor)
II (69)
M, LiCl (4 eq),
+
II (61)
L, THF, 0°, 2 h
THF, 0°, 2 h
96
II (95)
J, THF, 0°, 2 h
334
207
311
74
96
96
101
II (95)
K, CH2Cl2, rt, 2 h
i-PrOH, DCE, O2, rt
93
II (96)
G, 0°, 2 h
77
315
77
II (25)
(72)
II (96)
+
OH
Et3SiH, CsF, MeCN, 12 h
II
Refs.
II (36)
Ph
Product(s) and Yield(s) (%)
Et3SiH, TBAF, MeCN, 12 h
Et2O, rt, 24 h
PMHS (1 eq), ZnCl2 (1 eq),
Conditions
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)
311
I (93) I (89) I (96) I (93) I (75) I (91) I (96) I (84)
Et3SiH, TFA, CHCl3, rt, 15 min Et3SiH, TFA, CCl4, rt, 15 min Et3SiH, TFA, MeCN, rt, 15 min Et3SiH, Cl2CHCO2H, rt, 30 min Et3SiH, BF3•OEt2, rt, 1 h Et3SiH, EG acid, CH2Cl2, rt PhMe2SiH, EG acid, CH2Cl2, rt Et3SiH, TrClO4,
MeCN, 57-58°, 1 h
Cl3SiH (3 eq), (n-Pr)3N (1 eq),
C6H6, 80°, 20 min
(HMe2Si)2O, TMSOTf,
BnOTMS, CH2Cl2, 0°, 10 min
Et3SiH, TrClO4,
Ph
I (97)
I (72)
I (87)
Et3SiH, TFA, rt, 30 min
CH2Cl2, 0°, 10 min
I (80)
(HMe2Si)2O, TFA, EtOH, 30-40°
SiCl3
(5)
+ Ph
Cl
SiCl3 (42)
711
314
329
329
74
333
333
313
313
313
313
313
313
312
C7
Ph
O H
Aldehyde
V
VI
3h 3h 47 h 21 h 7h
40° rt rt rt rt
Fe-mont Cu-mont Na-mont silica Ca-Y-zeolite
(EtO)3Si Et3Si Et3Si Et3Si Et3Si
(87) (85) (87) (68) (69) (81) (26) (45)
CF3CO2H CCl3CO2H H2SO4 H2SO4 H2SO4 CF3CO2H CF3CO2H H2SO4
Me Me Et n-Pr i-Pr n-C7H15 t-Bu t-Bu
(87)
H2SO4
Me
Et3SiH (1.1 eq), ROH, acid, 28° Acid R
3h
rt
Fe-mont
PhMe2Si
(0)
(0)
(0)
(77)
(—)
(94)
OR
1h
rt
Fe-mont
Et3Si
Ph
Ph H Time
Temp
Catalyst
OSiR3
(86)
OSiMe2Ph
OSiEt3
VI (57)
Ph
V (96)
Ph
R3Si
R3SiH (1.5 eq), catalyst, MeC6H5
18-C-6 (0.05 eq), CH2Cl2, rt, 11 h
PhMe2SiH (1.1 eq), CsF (0.1 eq),
HMPA, rt, 1.5 h
PhMe2SiH (1.2 eq), TBAF (2 eq),
MeCN, rt, 10 h
Et3SiH (1.5 eq), CsF (1.5 eq),
MeCN, rt, 12 h
Et3SiH (1.4 eq), TBAF (1.4 eq),
Conditions
(91)
(36)
Product(s) and Yield(s) (%)
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)
328
324
347
320
76
76
Refs.
313
OTHP, Et3SiH (2.2 eq),
, Et3SiH (2.2 eq),
O
CH2Cl2, 0°, 2 h
TMSH, TMSI, c-C6H11OTMS,
OTMS , Et3SiH (1 eq), TMSOTf (2.0 eq), CH2Cl2, –78° to –30°
AcO BnO
O
OTMS , Et3SiH (1 eq), O TMSOTf (0.1 eq), CH2Cl2, 0° to rt
TMSI (0.3 eq), n-C5H12, –78° to rt, 5-6 h
1-AdOTMS (1.25 eq), TMSH (1.25 eq),
TMSOTf (10 mol%), MeCN, 0°, 1 h
Ph
OTHP
Ar OTHP, Et3SiH (2.2 eq), TMSOTf (10 mol%), MeCN, 0°, 1 h
OTHP , Et3SiH (2.2 eq), AcO TMSOTf (10 mol%), MeCN, 0°, 1 h
OTHP , Et3SiH (2.2 eq), BnO TMSOTf (10 mol%), MeCN, 0°, 1 h
TMSOTf (10 mol%), MeCN, 0°, 1 h
Ph
Ph
AcO
O
Ph
Ar
AcO
BnO
Ph
O
BnO
O
C6H11-c
OBn
O
(98)
(98)
Ar = 4-MeOC6H4
(96)
(89)
(75)
(98)
(95)
(95)
(97)
OBn
OBn
OBn
OBn
OBn
OBn
OBn
334
341
341
338
340
340
340
340
340
314
C7
Ph
O H
Aldehyde
Ph
Ph
Ph
Ph
VII
CH2Cl2, rt,
Et3SiH, EG acid, TMSOCH2C CH,
Ph
Ph
Et3SiH, H2SO4, EtOH, rt, 1 h
O
OEt
VII (85)
Et3SiH, Cl3CCO2H, MeOH, rt, 1 h
(98) OMe
(88)
TMSOTf Ph
(20)
TMSI
Et3SiH, TFA, MeOH, rt, 1 h
(96)
O
O
(87)
(87)
Ph
Ph
Ph
(95)
Ph (63)
(83)
(99)
(—)
(81)
Product(s) and Yield(s) (%)
C6H13-n
C7H15-n
BF3•OEt2
Ph
O
O
O
O
O
Sn(OTf)2
Catalyst
Ph OTHP, Et3SiH (2.2 eq), catalyst (10 mol%), MeCN, 0°, 1 h
PhMe2SiH, EG acid, TMSO(CH2)2OTMS, Ph CH2Cl2, rt,
CH2Cl2, 0°, 10 min
Et3SiH, Ph3CClO4, Ph(CH2)3OTMS,
CH2Cl2, rt,
PhMe2SiH, EG acid, Ph(CH2)3OTMS,
CH2Cl2, 0°, 10 min
n-C6H13CH(Me)OTMS,
Et3SiH, Ph3CClO4,
Et3SiH, TFA, n-C7H15 OH, rt, 1 h
Conditions
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)
333
328
328
328
340
333
329
333
329
328
Refs.
315 + Ph
O
Ph
Et3SiH, H2SO4, t-BuOH, rt, 1 h
, TBAF (6 mol%),
OSiMe2H
2. H3O+
THF, –78°, 3.5 h
1. Ph
PDMS (2.3 eq), K2CO3 (1 eq), 60°, 2.5 h
(EtO)3SiH (2.3 eq), KF (1 eq), rt, 36 h
ROTMS (0.83 eq), CH2Cl2
Et3SiH (1 eq), TMSOTf (0.1 eq),
TFA (4 eq), 50 to 60°
Et3SiH (1 eq), MeOH (2 eq),
2. Et3SiH, Nafion®-H, CH2Cl2, reflux, 3 h
O
O
O
O
O
Ph
OH
R
Temp
+
Ph IX
(0)
Ph
(16) 0° to rt
Ph
OH
(99)
c-C6H11
0° to rt
(92)
(81)
t-Bu
0° to rt
(99)
(96)
–78° to –30°
0° to rt
i-Pr
–30° to 0°
–78° to –30°
i-Bu
OH
H2C=CHCH2
Bn
R
(45)
(69)
(68)
(71)
VIII + IX (91), VIII:IX = 97:3
Ph
Bu-t
Pr-i
Pr-n
VIII
OH
II (100)
II (100)
Ph
VII (83)
VII (94.6)
Ph
Et3SiH, H2SO4, i-PrOH, rt, 1 h
1. HC(OMe)3, CH2Cl2, rt, 2 h
Ph
Ph
Et3SiH, H2SO4, n-PrOH, rt, 1 h
CH2Cl2, rt,
Et3SiH, EG acid, TMSOCH2CH=CH2,
400
83
83
341
327
335
328
328
328
333
316
C7
Ph
O H
Aldehyde
18 h
120° 120° 22°
22° 22°
MeC6H5 MeC6H5
MeCN MeCN MeC6H5 MeC6H5
4-FC6H4 4-MeOC6H4 MeC6H5 MeCN
Ph
PhO BnO t-BuO PhNH BnNH
18 h
18 h
18 h
18 h
18 h
CHCl3, rt, 5.5 h
Me2ClSiH (1.2 eq), InCl3 (5 mol%),
CHCl3, rt, 5.5 h
Me2ClSiH (1.2 eq), In(OH)3 (5 mol%),
22°
22°
18 h
120°
MeC6H5
Bn
18 h
36 h
120°
Solvent
R
Temp Time
RCONH2, PhCHO (x eq), solvent
Et3SiH (3 eq), TFA (2-3 eq),
, TBAF (6 mol%), –78°, 15 h
OSiMe2H
Conditions
XII
Ph
OSiMe2H
+
+
OH
OH
XI
XIII
Ph
OSiMe2H
Ph
OSiMe2H
Product(s) and Yield(s) (%)
XIV
R
Cl
(89)
(92)
(92)
(95)
(90)
(95)
(92)
(91)
(92)
(90)
x = 0.33
N H
O
(88)
(97)
(81)
(92)
(85)
(91)
(93)
(94)
(68)
x=3
X + XI + XII + XIII (75), X:XI:XII:XIII = 27:6:53:14
OH
Ph
OSiMe2H
XIV (60)
Ph
Ph
+
X
OH
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)
331
331
326
400
Refs.
317
Br
Cl
Ar
Ph
R1
Cl
O
O
O
Cl
O
H
D
H
H
O
O
H
H
i-Pr
n-C6H13
(34)
4-ClC6H4
2-ClC6H4
Ar
I
II (55)
I:II = 75:25
I + II (65)
(25)
314
(EtO)3SiH (1.1 eq), KF (1 eq), 100°, 1 h
MeCN, 51-64°, 1 h
Cl3SiH (3 eq), (n-Pr)3N (1 eq),
CHCl3, rt, 2 h
Me2ClSiH (1.2 eq), In(OH)3 (5 mol%),
In(OH)3 (5 mol %), CHCl3, rt, 2 h
Et3SiH (1.2 eq), TMSCl (1.2 eq),
C6H6, 80°, 20 min
(HMe2Si)2O, TMSOTf,
Br
Cl
I (34)
Cl
Cl
I
OH
SiCl3
Cl
II Ar = 4-ClC6H5 (90)
(90)
(61)
79, 80
711
331
331
314
333
Ar
586
II Ar = 4-ClC6H5 (86)
II
O
(86)
(92)
(94)
365
PhMe2SiH, EG acid, CH2Cl2, rt,
Ar
s-Bu
Ph
(74) 95% ee
t-Bu
Ph
(97)
(91)
313
+
D
i-Pr
Ph
R2
Ph
Ph
R1
II Ar = 4-ClC6H5 (80)
I
SR2
OH
ArBn
Ph
R1
Et3SiH, TFA, 0°, 10 h
C6H6, reflux, 3 h
PMHS, TMSOTf (cat.),
(–)-4, THF, rt
MesPhSiH2, [Rh(cod)Cl]2 (2.5 mol%),
2. Et3SiH, 0° to rt, 3 h
1. R SH, BF3•OH2, CH2Cl2, 0°, 1 min
2
318
C7
O 2N
O H
Aldehyde
ROTMS (0.83 eq), CH2Cl2, 0° to rt
Et3SiH (1.0 eq), TMSOTf (0.1 eq),
(Ph3P)CuH (3 mol%), MeC6H5, 2 h
PhMe2SiH (1.3 eq),
B (1 eq), rt, 12 h
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
Et2O, rt, 24 h
PMHS (1 eq), ZnCl2 (1 eq),
KF (1 eq), 100°, 2 h
(EtO)3SiH (2.3 eq),
C (1 eq), rt, 12 h
CH2Cl2, 30°, 2 h
(HMe2Si)2O, TMSOTf,
Et3SiH, TFA, rt, 5 h
Conditions
O2N
O2N
I (100)
I (80)
I (65)
O2N
I (100)
I (55)
O2N
O
R
(89)
NO2
(73) (63)
t-Bu
(88)
(33)
i-Pr
n-C6H13
R
(80)
OSiMe2Ph
I
OH
I
O
Product(s) and Yield(s) (%)
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)
341
317
84
367
315
83, 80, 79
84
314
313
Refs.
319
C7-8
Ar
Ph
R
30° 80° 80° rt –78° 30° 80° rt
C6H6 C6H6 TFA CH2Cl2 CH2Cl2 C6H6 TFA
2-ClC6H4
4-ClC6H4
4-ClC6H4
4-O2NC6H4
4-O2NC6H4
4-HO2CC6H4
4-HO2CC6H4
TMSOTf (cat.), solvent
HMe2SiOSiMe2H (1.0 eq),
MeC6H5, rt
Temp
R
240 min
120 min
120 min
70 min
30 min
20 min
(46)
(97)
(55)
(9)
(94)
(90)
(94)
O
(97)
I
H
OH
OH
N
BnO
20 min
Ar
Ph
R
AcO
20 min
Time
Ph3SiH (1 eq), (C6F5)3B (2 mol%),
C6H6
Ph
O
Solvent
+
Et2O, rt
(MeO)3SiH (1.3 eq), LiOMe (1.2 eq),
18-C-6 (0.5 mol%), CH2Cl2, rt, 1 h
PhMe2SiH (1.1 eq), CsF (10 mol%),
Ph
H
H
H
H
O
Ar
O
O
O
N
, Et3SiH (1 eq), OTMS TMSOTf (2.0 eq), CH2Cl2, –78° to –30°
AcO BnO
O
Arr
(52)
II
R
OEt
>99:1
6:1
I:II
R
Ph
(80)
6h
n-C7H15
Me
(86)
15 h
4-MeOC6H4
OH
(55)
(85)
15 h
20 h
Time
(58)
NO2
2-O2NC6H4
Ph
R
OSiMe2Ph
+
O
O
314
116
91
345
341
320
C7-8
X
Ar
R1
H
PhMe2Si
n-C6H13
O
PhMe2Si
4-ClC6H4
H
PhMe2Si
4-MeC6H4
O
PhMe2Si
Ph
OTHP, Et3SiH (2.2 eq),
Ph3SiH (1 eq), (C6F5)3B (2 mol%)
TMSOTf (10 mol%), MeCN, 0°, 1 h
Ph
n-C5H12, –78° to rt, 5-6 h
t-BuOTMS (1.25 eq),
Me3SiH (1.25 eq), TMSI (0.3 eq),
Et3Si
Ph
LiClO4 (0.1 eq), CH2Cl2, electrolysis
R23SiH (1.2 eq), n-Bu4NClO4 (0.1 eq), R23Si
H
Conditions
X
Ar
Ar
R1
R1
O
OBu-t
(91.8)
(86.3)
(94.5)
(95.7)
(91.0)
O
OSiPh3
Ph
(21) (64)
2-MeOC6H4 Ar
(90) (98)
4-MeOC6H4 4-MeC6H4
(82) (81) (96)
Me Cl NO2
H
(81)
(90) 4-O2NC6H4
X
(95)
(98) 4-ClC6H4
Ph
(87)
2-MeC6H4
(71)
4-MeC6H4 3-MeC6H4
(77)
(67)
4-FC6H4
Ph
Ar
Product(s) and Yield(s) (%)
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)
R1
O
Aldehyde
115
340
338
333
Refs.
321
C7-9
R1
Ar
R
R1
O
O
O
O
10 min 10 min 5 min
4-MeOC6H4 4-NCC6H4 4-O2NC6H4
(n-Bu)4NClO4 (0.1 eq),
PhMe2Si Et3Si Et3Si PhMe2Si Et3Si
Bn(CH2)2 H2C=CHCH2 HC CCH2 (CH2)2OTMS H2C=CHCH2 HC CCH2
Ph Ph Ph Ph (E)-PhCH=CH (E)-PhCH=CH
R33Si
Bn(CH2)2
Et3Si
PhMe2Si
R2
n-C6H13
LiClO4 (0.1 eq), CH2Cl2, electrolysis
R1
H
R33SiH (1.2 eq), R2OTMS,
MeC6H5, rt
Ph3SiH, (C6F5)3B (2 mol%),
Time 11 min
Ph
2. BF3•OEt2, rt
1. Et3SiH, BF3, CH2Cl2
CH2Cl2, rt, 5 h
InCl3 (20 mol%), R2STMS (1.2 eq),
R
H
H
H
Et3SiH (1.2 eq), TMSCl (50 mol%),
R1
Ar
R
R1
O
R2
OH
(100)
(100)
(0)
(—)
I
OH
(49.8)
(51.1)
(63.2)b
(95.0)
(71.2)
(98.8)
(81.9)
I
SR2
(0)
(0)
(100)
(52)
II
+
i-Pr Ph Et
Ph Ph BnCH2
(82) (81) (96)
4-ClC6H4 4-O2NC6H4
(87)
(78)
(81)
(82)
(83)
(87)
4-MeC6H4
Ph
Ar
RMe II
Et
Et
Ph
n-C8H17
R2
R1
333
116
1
426
322
C7-9
R
1
R2 BnCH2CH2 BnCH2CHMe HO2C(CH2)11 Et n-C9H19 Bn BnCH2CH2 BnCH2CHMe BnCH2CH2 BnCH2CH2 BnCH2CHMe BnCH2CH2 BnCH2CHMe
c-C6H11
Ph
Ph
Ph
Ph
Ph
Ph
Bn
BnCH2
BnCH2
n-C7H15
n-C7H15
R OH, CH2Cl2, rt
2
Et3SiH (1.3 eq), BiCl3 (0.11 eq),
c-C6H11
H
Conditions
R1
(64)
(63)
(69)
(73)
(61)
(82)
(93)
(80)
(95)
(74)
(38)
(70)
(77)
O
R2
Product(s) and Yield(s) (%)
TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)
R1
O
Aldehyde
332
Refs.
323
C7-8
Ar
H H H Me Me H H H
(E)-PhCH=CH
BnCH2
Ph
(E)-PhCH=CH
Ph
(E)-PhCH=CH
(E)-PhCH=CH
X, PhSiH3 (2 eq),
H
H
Me
Me
H
H
H
H
H
R3
OMe
OMe
NMe2
NMe2
NMe2
NMe2
NMe2
NMe2
NMe2
X
(10)
50:50
(80)
20 h
20°
Time 20 min 60 min 45 min 180 min 195 min 15 min 150 min 180 min
2-ClC6H4
4-ClC6H4
4-O2NC6H4
3-HOC6H4
4-MeC6H4
4-MeOC6H4
4-MeO2CC6H4
ZnI2 (cat.)
–70°
–70°
70°
–70°
–70°
70°
70°
70°
Temp
Ar
Cl
II (—) (45) (—) (20) (—) (—) (40) (40)
I (55) (85) (80) (40) (87) (60) (60)
O
(91)
+ Ar
Ar II
(14)
—
(70)
4h
20°
I
(31)
—
(50)
5h
20°
(14)
(12)
72:28
(68)
4h
20°
50:50
(10)
70:30
(72)
3h
50°
(62)
(trace)
70:30
(90)
6h
20°
20 h
(3) (trace)
72:28
(96)
4h
20°
20°
III
I:II 80:20
R1
(95)
+
I + II
I
X
OH
2h
R2
R3
O
20°
OH
Temp Time
TMSCl (1.57 eq), SO2Cl2 (1.37 eq),
HMe2SiOSiMe2H (1.0 eq),
Ph
H
Ar
O
H
R2
Ph
2. H3O+
R1
BnCH2
O R1 R3 Co(dpm)2 (0.05 mol%), DCE, temp
1. R2
R2
X II
R3
O + R1 OH III
314
478
324
C7-9
R
Ar
Ar
O
O
O
(70) (66) (75) (75) (83)
10 min 10 min 15 min 45 min 8 min
4-MeC6H4
4-MeOC6H4
4-NCC6H4
4-MeO2CC6H4
2,4-Me2C6H3
H
(87)
5 min
3-HOC6H4
O
(72)
10 min
2-ClC6H4
Et3SiH (1.2 eq), BiBr3, (10-30 mol%), rt
(80)
10 min
Ph
Ar
I2 (0.6 eq), CH2Cl2, –5° Time
R
(84)
15 min
4-MeOC6H4
R
(80)
80 min
4-MeO2CC6H4
R
(97)
20 min
4-MeC6H4
HMe2SiOSiMe2H (1.0 eq),
(77)
45 min
3-HOC6H4
H
(90)
20 min
I
(64)
15 min
2-ClC6H4
4-ClC6H4
I
+
(94)
Ar
Br
30 min
I
Ph
Ar
Ar
TMSCl (1.5 eq), LiBr (1.7 eq),
HMe2SiOSiMe2H (1.0 eq),
Conditions
98)
(>98)
(>98)
(50)
(77)
(84)
OH
R2 Me Ph
Ph Ph
—(CH2)5—
R1
4h Ph
(30)
(40)
(70)
(73)
15 h (53) Me
Time
0.5
(50) Ph R
1.0
0.5
x (80)
(36)
Me
Me
R
78
288
750
378
388
C8-17
C8-13
Ar
R1
Ar
O
O
O
R
R2
R
Me Et ClCH2CH2 Me
p-ClC6H4 Ph Ph PhCH2CH2
p-NO2C6H4
Ph Ph
Ph
p-EtO2CC6H4 Me
R
Ar
Ketone
Et3SiH (x eq), TFA (y eq), solvent, rt
Et3SiH (1.1 eq), H2SO4, H2O, MeCN, 28°
1 h; 60°, 2 h
2h
1 h; 60°, 3 h
2h
1 h; 60°, 3 h
2h
2h
InCl3 (5 mol%), CH2Cl2, rt
Me2ClSiH, TMSCH2CH=CH2,
Conditions
Ar
R1
Ar
R
R2
NHAc
(75)
(99)
(44)
mixture
(70)
(67)
(84)
R
R2 Me Ph
Ph Ph
—(CH2)5—
R1
(85) (63)
48 h
(30) 72 h
72 h
Time
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
73
313
427
Refs.
389
C8-18
R1
O
10.0 5.4 9.5 10.0 6.5 9.9 5.0 7.0 15.0 7.7 6.7
2.5 2.2 2.5 2.6 2.2 2.2 2.2 5.0 2.4 2.2 2.4 3.0 2.2
Et n-Pr i-Pr c-C3H5 n-Bu HO2C(CH2)3 c-C4H7 c-C4H7 HO2C(CH2)4 Ph Ph Ph n-C10H21
Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph 4-O2NC6H4 4-HO2CC6H4 Ph
R2 H H H H Me Ph TMS H
1
Et t-Bu c-C6H11 Ph Ph Ph Ph 2-MeC6H4
R
5.4
4.4
BrCH2
Ph
R2
7.0
2.2
Me
4-ClC6H4
y
Me
Ph
TFA
CCl4-TFA
TFA
TFA
TFA
CCl4-TFA
H2O-TFA
TFA
TFA
H2O-TFA
TFA
TFA
TFA
TFA
TFA
TFA
Solvent
MeC6H5, 0°, 1 h
Et3SiH, (C6F5)3B (2 mol%),
10.0
6.7
10.0
x 2.2
R
Ar
Time
15 min
120 h
47 h
15 min
5.5 h
7.5 h
6h
48 h
15 min
7h
15 min
15 min
15 min
44 h
200 h
15 min
R1
OH
(100)
(100)
(100)
(100)
(100)
(26)
(25)
(100)
(100)
(48)
(100)
(100)
(100)
(93)
(100)
(100)
I
5.0:1 3.0:1 7.7:1 15:1
(100) (100) (94)
7.0:1
5.0:1
>30:1
4.4:1
I:II
R1
(100)
(90)
(93)
(100)
(100)
I + II
R2
+
OH
II
R2
372
390
C9
O
O
Ketone
BF3•OEt2 TFA (6.8 eq) H2SO4 H2SO4 H2SO4 H2SO4
Et3Si Et3Si n-BuH2Si Et2HSi Et3Si (n-Bu)3Si
(t-Bu)2SiH2 (1 eq), TFA (6.6 eq), rt, 20 h
Et3SiH (1.1 eq), acid, rt
BF3•OEt2 BF3•OEt2
n-BuH2Si
Acid Catalyst
Et2HSi
R3Si
2. Aq. OH–
0° to rt, 24 h
1. R3SiH (1.1 eq), acid catalyst (1 eq),
DMSO, 60°, 7 h
PMHS (1.5 eq), KF•2H2O (1 eq),
DMF, 60°, 5.5 h
Me(EtO)2SiH (1.5 eq), KF (1 eq),
(EtO)3SiH (1 eq), CsF, rt, 1 h
Conditions
I:II
I
OH
I
O2CCF3
I + II (100)
11:89
10:90
15:85
26:74
16:84
5:95
9:91
13:87
I (85)
I (75)
I
OH
(11)
+
90:10
TFA H2SO4
+
84:16
BF3•OEt2
II
(89)
I + II (—)
O2CCF3
I:II 95:5
Acid
II
OH
(95)
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
386
74
381, 384
82
82
80
Refs.
391
O
O
O
O
O
O Pr-n
MeC6H5, –20°
Ph2SiH2 (1.0 eq), Cp2Ti(PPh3)2,
MeC6H5, –20°
Ph2SiH2 (1.0 eq), Cp2Ti(PPh3)2,
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
(Ph3P)4RhH (0.4 mol%), CH2Cl2, rt, 7 h
Ph2SiH2 (1.3 eq),
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
TFA (6.6 eq), rt, 20 h
(t-Bu)2MeSiH (1 eq),
HO
I
HO
I
OH +
OH
(85), exo:endo = 36:64
II I + II + III (85)
OH
+
II
HO
Pr-n +
(53), endo:exo = 1:7
+
O
(40)
III
III
OH
OH
II
+
OH
Pr-n
III
OH
I + II (56), (I + II):III = 16:1, I:II = 13:1
+
HO
I + II (64), (I + II):III = 23:1, I:II = 22:1
Pr-n
I
O
OH
I (99:1
NMe2
I + II (94), I:II = 2:98
NEt2
OH
OH
O
Ph O I + II (97), I:II = 6:94 I + II (19), I:II = 68:32
Ph
(81)
TMSOTf
OH
6:1:2 20:1:1.3
(67)
(MeO)3SiH (1.2 eq), LiOMe (0.04 eq),
I:II:III
I + II + III
OH
+
BF3•OEt2
I
O
Pr-i
+
II
OH
(90) + Ph2SiHCl (—)
Product(s) and Yield(s) (%)
OEt
NMe2
NEt2
O
I + II (97), I:II = 98:2
n-Bu
I
OH
NC
OH
Catalyst
CH2Cl2, –78°, 6 h; 0°, 12 h
Ph3SiH (4 eq), catalyst (2.2 eq),
TBAF (5-10 mol%), HMPA, rt, 12 h
Ph2SiH2 (1.1-1.2 eq),
TBAF (5-10 mol%), HMPA, rt, 10 h
PhMe2SiH (1.1-1.2 eq),
PhMe2SiH (1.2 eq), TFA, 0°, 3 h
CH2Cl2, 20°, 19 h
Ph2SiH2 (1.2 eq), AlCl3 (1 eq),
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
366
366
407
320
320
87, 276
373
Refs.
393
O Ph
+ n-C11H23
O OEt
Ph
I
Ph
OH
(0)
354
83
MeC6H5, 22 h
317
n-C11H23
II (78)
+
749
749
749
PMHS (2.5 eq), (Ph3P)CuH (3 mol%),
(86)
(100)
(100)
749
749
80
Ph
Ph
Ph
(95)
366
II (70)
II
HO
I (96)
I (99)
I
t-BuMe2SiO
I (98)
Et3SiO
I + II (96), I:II = 4:96
(EtO)3SiH (1 eq), CsF, rt, 1 h
CH2Cl2, rt, 5-20 min
PMHS (3 eq), (C6F5)3B (5 mol%),
(EtO)2MeSiH (2.3 eq), CsF (1 eq), rt, 5 h
neat, 150°, microwave, 15 min
NaOMe (3 mol%), o-dppb (0.05 mol%),
t-BuMe2SiH (1.2 eq), CuCl (0.5 mol%),
MeC6H5, rt, 90)
Catalyst
R3Si
R3SiH, Triton-B or TBAF
390
316
278
400
C10
t-Bu
O
Ketone
II
23:77 11:89 12:88 19:81 12:88
46:54 57:43
20 h 3h 1.5 h 64 h 24 h 12 h 20 h 18 h 0.25 h 0.25 h
80° 110° rt 80° 80° 80° 80° rt rt
Et3Si Et3Si Ph3Si Ph3Si PhMe2Si (EtO)3Si Cl3Si Et2HSi Ph2HSi
12:88 41:59
20 h 24 h 10 h 12 h 12 h
Et3Si Ph3Si PhMe2Si Et2HSi Ph2HSi
I:II
8h
Et3Si
49:51
7:93
5:95
8:92
Time
R3Si
2. TsOH, aq. MeOH, rt, 1 h
C6H6, 80°
1. R3SiH (1.5 eq), (Ph3P)3RuCl2 (2 mol%), I + II (60-90)
37:63
29:71
29:71
33:67
144 h
rt 45°
I:II
Time
Et3Si
Temp
t-Bu
+
I
(—)
OH (—)
Product(s) and Yield(s) (%)
t-Bu
OH
Et3Si
R3Si
2. TsOH, aq. MeOH, rt, 1 h
(Ph3P)3RhCl (2 mol%), C6H6
1. R3SiH (1.5 eq),
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
391
391
Refs.
401
0° 5°
87 72
4h
1d
4h
Time
I:II
I + II + III (70) +
MeCN, 28°, 65 h
Et3SiH (1.1 eq), H2SO4, H2O,
III
O
(74) 39:61
(92) 33:67
(87) 35:65
I + II
t-Bu
I + II
I + II (98), I:II = 1:14
CH2Cl2, rt, 2 h
Et3SiH (2 eq), TMSOTf (0.1 eq),
rt
Temp
95
Ligand
ligand (2 mol%), AgBF4 (2 mol%), THF
Ph2SiH2 (1.5 eq), (Ph3P)3RhCl (1 mol%),
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
CH2Cl2, rt, 5 h
Ph2SiH2 (1.3 eq), (Ph3P)4RhH (0.3 mol%), I + II (81), I:II = 16:84
t-Bu
(4) +
Bu-t
t-Bu
NHAc
(100)a
(21)
313
334
572
367
374
402
C10
t-Bu
O
Ketone
0.49
(83)
6.8 7.5 7.0 7.0
0.8 1.0
0.83
Et3Si (c-C5H9)3Si 0.75 1.1
PMHS
(i-Bu)3Si (s-Bu)3Si
(t-Bu)2SiH2 (1 eq), TFA (6.6 eq), rt, 2 h
7.0
0.23
(66)
2.1
1.05
n-PrH2Si
1.22
1.08
0.79
0.25
+
IX
t-Bu
(6)
(14)
(11)
(17)
(34)
(50)
(74)
VIII
O
VI
O
Bu-t
Bu-t
3
18
13
25
30
53
67
VI (%)
24
43
35
48
55
40
29
73
39
52
27
15
7
4
Refs.
72, 74
386
VII (%) VIII (%)
trans, trans cis, trans cis, cis
(3)
t-Bu
Bu-t
t-Bu
+
VI + VII + VIII
VII
IV (66) + V (31) +
(94)
(86)
(89)
(50)
0.031
2.5
1.0
n-BuH2Si (26)
y
x IV + V
+ t-Bu
V
IV O
t-Bu
IV:V
+
O2CCF3
Product(s) and Yield(s) (%)
t-Bu
O2CCF3
R3Si
R3SiH (x eq), TFA (y eq)
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
403 (t-Bu)2MeSiH (1.17 eq), TFA (3 eq), rt
(t-Bu)3SiH (1.2 eq), TFA (3 eq), rt
94 97
264 h 720 h
+
I
IV
(—)
(—)
(—)
(10)
(9)
+
IV IX (5.5)
+
IX
(10)
(9.3)
(9)
X (3)
(1.8) (27)
0.6 h (0.7) (70) (27) (6) (41) (18) (8) (28) (10) (8) (27)
21 h 46 h 96 h
(39)
(38)
I + IV
IX XIV XV
Time
(20)
(16)
(7)
(0.5)
II + V
(18)
(50) (6.5) (38)
O2CCF3 386
(3)
(1.2)
(0.8)
(0.6)
(0.5)
(10)
(20)
(51)
(57)
(64)
386
XI XII + XIII
t-Bu XI
(22) (4.2)
OSiMe(Bu-t)2
(8)
+
(9.3) (7.4) (3.7)
(8)
V
t-Bu XIII
t-Bu XV
V
(21)
(13)
(13)
(12)
(10)
+
X t-Bu OSi(Bu-t)3
O2CCF3
t-Bu XIV
+
OSiMe(Bu-t)2
+
85
93 h
II
53
27 h
+
50
I
% Conv.
21 h
t-Bu XII Time
+
OSi(Bu-t)3
I + IV + V + IX +
404
C10
t-Bu
O
Ketone
In(OH)3 (5 mol%), CHCl3, 60°, 2 h
Me2ClSiH (1.2 eq),
Et3SiH (1.1 eq), HCO2H (2.0 eq), rt
TBSOTf (0.01 eq), rt, 2 h
TBSH (3 eq),
t-Bu
Cl
t-Bu
Refs.
(76) cis:trans = 12:88
331
74
XVII + XVIII (81), XVII:XVIII 66:34 392
(100) cis:trans = 38:62
XVIII
XVII OCHO
t-Bu
t-Bu
+
74
III (55) + XVI (55) cis:trans = 60:40
Et3SiH (1.1 eq), AlCl3 (0.1 eq), rt OTBS
74
III (50) + XVI (50) cis:trans = 42:58
Et3SiH (1.1 eq), SnCl2 (0.1 eq), rt
OTBS
74
XVI (100) cis:trans = 61:39
74
74
Et3SiH (1.1 eq), BF3•OEt2 (3.0 eq), rt
XVI
(100) cis:trans = 32:68
Product(s) and Yield(s) (%)
XVI (100) cis:trans = 67:33
t-Bu
OSiEt3
Et3SiH (1.1 eq), ZnCl2 (0.1 eq), rt
Et3SiH (1.1 eq), ZnCl2 (1.0 eq), rt
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
405
O
O
O
O
CH2Cl2, rt, 2 h
Et3SiH (2 eq), TMSOTf (0.1 eq),
CH2Cl2, rt, 1 h
Et3SiH (1.3 eq), BF3•OEt2 (4-6 eq),
CH2Cl2, 0° to rt, 2 h
Et3SiH (1.5 eq), CF3SO3H (4 eq),
2. EtMe2SiH (2.2 eq), 0°, 60 min
1. BF3, CH2Cl2, 0°
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
n-C6H14, rt, 6 h
Et3SiH (1.5 eq), H2SO4/carbon,
PMe3 (60 mol%), MeC6H5, –20°
PhMeSiH2 Cp2Ti(PMe3)2 (10 mol%),
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
H I
I
+ H II
OH
(22)
+
III
OH
(100)
(99)
(95)
II (78)
III
O
I (79)b + II (20)b
OH
OH
(100)a
I + II:III = 6:1, I:II = 70:1, I + III (72)
OH
OH
II
HO
334
217
420
1
367
243
428, 429
367
406
C10
O
O
Ketone
CH2Cl2, 0° to rt
n-C6H13OTMS (0.83 eq),
Et3SiH (1 eq), TMSOTf (1 eq),
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
(EtO)3SiH (1 eq), CsF, rt, 1 min
c-C6H11OTMS, CH2Cl2, 0°, 2 h
Et3SiH, TMSOTf, TMSI,
reflux, 3 h
2. Et3SiH, Nafion®-H, CH2Cl2,
1. HC(OMe)3, CH2Cl2, rt, 2 h
CH2Cl2, rt, 2 h
Ph3CH (0.1 eq), 220 (0.09 eq),
TMSH (xs), TMSCl (cat.),
CH2Cl2, rt, 2 h,
TMSH (xs), 220 (0.09 eq), Ph3CCl (0.1 eq),
Conditions
II
I (trace)
I
+
I + II + III (98), I:II:III = 8:15:75
+
(93)
OC6H13-n
OH
(100)a
(88)
(95)
OC6H11-c
OMe
I + II + III (75), I:II:III = 26:40:29
I
OH
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
III
O
341
367
80
334
335
424
424
Refs.
407 O
Br
O
0.1 0.1 0.1 1.0 0.1
PhMeHSi Ph2HSi Et3Si PhMe2Si none
hexane
none
none
none
none
Solvent
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
(EtO)3SiH (1.1 eq), CsF (1 eq), 70°, 3 h
0.1
Ph3Si
mmol Cat.
Et2HSi
R3Si
R3SiH, (Ph3P)3RhCl, solvent, 0-80°
OH
Br
OH
OSiR3
H
I II (9)
(0)
(trace)
(60)
(0)
(30) (70)
(73) (27)
(75) (25)
(91)
(90) (10)
I
+ H II
OSiR3
367
79, 80
388
408
C10
O
O
O
Ketone
0.1
PhMe2Si none
hexane
none
none
none
none
Acid Catalyst HOAc HOAc BF3•OEt2
R3Si n-BuH2Si Et3Si Et3Si
0° to rt, 24 h
R3SiH (1.1 eq), acid catalyst (1 eq),
P(tm-tp)3 (2 mol%), C6H6, rt, 20 h
[Rh(C2H4)2]2 (0.5 mol%),
PhMe2SiH (1.2 eq),
1.0
Et3Si
0.1
PhMeHSi 0.1
0.1
Et2HSi Ph2HSi
0.1
mol% Cat. Solvent
Ph3Si
R3Si
R3SiH, (Ph3P)3RhCl, solvent, 0-80°
reflux, 3 h
2. Et3SiH, Nafion®-H, CH2Cl2
1. HC(OMe)3, CH2Cl2, rt, 2 h
Conditions
II
(0)
(0)
(64) (36)
(85) (15)
(86) (14)
(83) (17)
(90) (10)
I
+
I
OH
II
64:36
39:61
18:82
I:II
I + II (—)
+
I + II (92), I:II 45:55
I
OH
OMe
(88)
II
HO
OH
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
384
389
387, 388
335
Refs.
409
O
O
O NEt2
NHPh
O
OH
O
O
O Pr-i
OH
O
DMPU, 0°, 22 h
PhMe2SiH (1.2 eq), TASF (10 mol%),
PhMe2SiH (1.2 eq), TFA, 0°, 6 h
(EtO)3SiH (2.3 eq), CsF (1 eq), rt, 10 min
2. SnCl4, CH2Cl2, –80°
1. (i-Pr)2SiClH, Et3N, DMAP, hexane
2. SnCl4, CH2Cl2, –80°
1. (i-Pr)2SiClH, Et3N, DMAP, hexane
I
I
O
NEt2
+
(90)
O
Pr-i
III
Si
II
Si
H
O
Pr-i
OH
Pr-i
OH
II
O NEt2
I + III (75), I:III = 300:1
O
I + II (91), I:II = 2:98
O
NHPh
O
i-Pr
II
O
i-Pr
H
I + II (82), I:II 250:1
O
I + II (93), I:II 23:77
OH
OH
+
O
I
—
Pr-i
(47) i-Pr
>99:1
(81)
+
+
TMSOTf
OH
Pr-i
BF3•OEt2
Si
H I:II
I
O I + II
H
Catalyst
CH2Cl2, –78°, 6 h; 0°, 12 h
Ph3SiH (4 eq), catalyst (2.2 eq),
87, 276
87, 276
80, 83
397
397
407
410
C10
Ph
Ph
O
O
O
O
O
CO2Et
OMe
Ketone
O
CH2Cl2, 20°, 20 h
OMe
Ph
(90)
95:5 73:27
(EtO)3SiH OH
95:5
(MeO)3SiH
Ph2SiH2 (1.2 eq), AlCl3 (1 eq),
95:5
(TMSO)3SiH
I + II (>90)
+
II
II
OH
HO
I:II = 90:1
I (78), I + II:III = 99:1
+ Ph2HSiCl (—)
(39) 93% ee
(67)
CO2Et III
OH
+ EtO2C
PMHS
I
OH
OH
+
I
OH
I:II
Ph
Ph
EtO2C
Product(s) and Yield(s) (%)
Silane
Silane, Triton-B
Li-(R)-BINOL (10 mol%), 0°, 24 h
(MeO)3SiH (1 eq), Et2O:TMEDA (30:1),
CH2Cl2, rt, 6 h
Et3SiH (1.3 eq), BF3•OEt2 (4-6 eq),
MeC6H5, 21°
Ph2SiH2 (1.0 eq), Cp2Ti(PPh3)2,
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
373
278
592
217
428
Refs.
411
Ph
Ph
Ph
Ph
O
O
MeO
Ph
O
O
CF3
O
O
CO2H
NHCOCF3
MeO
O
LiI, CHCl3, rt, 11 h
Me2ClSiH (1.2 eq), In(OH)3 (5 mol%),
CHCl3, 60°, 3 h
Me2ClSiH (1.2 eq), In(OH)3 (5 mol%),
CHCl3, 0°, 0.3 h
Me2ClSiH (1.2 eq), In(OH)3 (5 mol%),
Et3SiH (2.2 eq), TFA, rt
reflux, 2 h; rt, 16 h
Et3SiH (4 eq), BF3•OEt2 (20 eq),
reflux, 2 h; rt, 16 h
Et3SiH (3.42 eq), TFA,
MeC6H5, rt, 4 h
CuCl (0.5 mol%), NaOBu-t (3 mol%),
TBSH (1.2 eq), 123 (0.1 mol%),
CH2Cl2, 20°, 22 h
Ph2SiH2 (1.2 eq), AlCl3 (1 eq),
Ph
Ph
Ph
O
Ph
Ph
O
O
OH
CF3
I
Cl
Cl
Ph
(74)
(92)
(78)
+ Ph
(78)
(50)
CO2H
+ Ph2SiHCl (—)
(90)b 80% ee
(30)
(86)
NHCOCF3
NHCOCF3
MeO
OH
MeO
Ph
OH
(14)
331
331
331
73
376
376
749
373
412
C11
R
C10-23
1
O
O
O
O
R2
97:3
(71)
BzO
Ph
O
26:74
(88)
BnNH
Ph
H
100:0
(80)
N-piperidinyl
Ph
O O OEt
Pr-i
DMF, 30°, 5 h
PMHS (1.2 eq), KF•2H2O (1.3 eq),
CH2Cl2, –78° to 20°, 12 h
Ph3SiH (4 eq), BF3•OEt2 (2.2 eq),
CH2Cl2, 0°, 2 h
O
O
(59)
OH
Pr-i
II
R2
OH
(81) cis:trans > 20:1
(50) trans:cis = 1:1
(95)
Ph O
95:5 100:0
(90)
Bn2N Bn2N
Me
OH
100:0
(87)
BnMeN
Ph
97:3 100:0
(76)
Et2N
(76)
Ph
73:27
(79)
AcO
87:13
(77)
Ph
I:II
I + II
BnO
R1
MeO
+
Me
I
R2
OH
Ph
R
1
Product(s) and Yield(s) (%)
R2
Ph2MeSiH (2 eq), TMSOTf (1 eq),
THF, 0-5°, 2 h
PMHS, (2-2.5 eq), TBAF (1 eq),
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
R1
Ketone
82
407
336
401
Refs.
413
i-PrO
Ph
O
H
Me2Si
O
O
O
O
H
O
O
O
O CF3
O O
O
OMe
OPr-i
+
(53)
H O
OH CF3
(EtO)3SiH (1 eq), CsF, rt, 0.5 h
Me(EtO)2SiH (2.3 eq), CsF, rt, 2.5 h
Me(EtO)2SiH (1 eq), CsF, rt, 2.5 h
TFA (0.2 eq), –80°, 30 min
rt, 15 min
ZnCl2 (0.25 eq), –80°, 30 min;
i-PrO
Ph
Ph
O
O
OH
OH
O
O
O
OMe
I + II (—), I:II = 2:1
I + II (—), I:II = 1:4
OPr-i
(85)
(85)
(70)
I + II (—), I:II = 1:6
79, 80
83
80, 83
399
399
399
399
ZnBr2 (0.12 eq), –80°, 8 h; rt, 16 h
399
399
410
I + II (—), I:II = 23:1
(—)
409
I + II (—), I:II = 14:1
+ O O O Si Si Me2 Me2 I + II (37), I:II = — II I
(58)
CF3
MgBr2•OEt2 (0.1 eq), rt, 24 h
O
H O
O CF3
O O
BF3•OEt2 (0.5 eq), –80°, 2 h
SnCl4 (0.1 eq), –80°, 2 h
PMHS, TFA, rt, 2 d
20°, 20 min
Et3SiH (4 eq), TFA (36 eq),
414
C11
Ph
Ph
Ph
O
O
OMe
NEt2
NEt2
OAc
NMe2
O
O
O
O
O
O
Ketone
TBAF (5-10 mol%), HMPA, 0°, 20 h
PhMe2SiH (1.1-1.2 eq),
TBAF (5-10 mol%), HMPA, rt, 12 h
PhMe2SiH (1.1-1.2 eq),
TASF (10 mol%), DMPU, rt, 12 h
PhMe2SiH (1.2 eq),
PhMe2SiH (1.2 eq), TFA, 0°, 3 h
PhMe2SiH (1.2 eq), TFA, 0°, 16 h
DMPU, 0°, 24 h; rt, 72 h
PhMe2SiH (1.2 eq), TASF (10 mol%),
PhMe2SiH (1.2 eq), TFA, 0°, 20 h
Conditions
Ph
Ph
Ph
Ph
I
I
I
I
OH
Ph
OMe
Ph
+
Ph
I + II (—)
+
OH
OH
OH
I + II (87), I:II 99:1
(95)
S
98:2
(95)
Cl
(46)
Ar
4-ClC6H4
+
(84)
(64)
I:II
NHCO2Me
CO2H
O
OEt
94:6
I
O
OH
O
(97)
Ar
s-Bu
Ph
Cl
MeO2C
OMe
I + II
2. PhMe2SiH, TiCl4, CH2Cl2, –78° to rt
1. TMSCl, Et3N
rt, 4 h
Et3SiH, TFA, LiClO4 (0.01 eq),
In(OH)3 (5 mol %), CHCl3, rt, 2 h
Me2ClSiH (1.2 eq),
In(OH)3 (5 mol%), CHCl3, rt, 3.5 h
Me2ClSiH (1.2 eq),
Cl
CO2H CO2Me II
N
Product(s) and Yield(s) (%)
Ph
NHCO2Me
O
O
OEt
OMe
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
Ar
O
OH
O
O
Ketone
421
423
331
331
Refs.
417
C11-16
Ph
O R1
PhMe2Si
OEE 0°
0°
–50° 18 h
6h
12 h
3h
rt
(i-PrO)Ph2Si
OAc (i-PrO)3Si
14 h
rt
Ph2MeSi
OAc
PhMe2Si
14 h
rt
PhMe2Si
OAc
OBz
4h
(4-MeOC6H4)Me2Si 0°
OAc
OAc
4h
0°
(4-MeC6H4)Me2Si
4h
OAc
4h
0°
(4-CF3C6H4)Me2Si
0°
PhMe2Si
OAc
20 h
OAc
Time
0°
PhMe2Si
OAc
Temp
R3Si
R1
TBAF (5-10 mol%), HMPA
R3SiH (1.1-1.2 eq), Ph I
OH
(55)
(82)
(71)
(91)
(89)
(99)
(88)
(83)
(72)
(93)
(95)
I + II
R1
90:10
96:4
78:22
86:14
92:8
93:7
93:7
93.1:6.9
93.1:6.9
93.3:6.7
95:5
I:II
+ Ph II
OH R1 320
418
C11-16
R
AlCl3 (1 eq) TFA TFA TFA AlCl3 (1 eq)
CO2Me NMe2 NHCO2Me NHCO2Et NHCO2Et
Ph
Ph
Ph
Ph
Ph TFA TFA TFA TFA
NHCO2Et NHCO2Me OBn NHSO2Ph OBz
Ph
2,5-(MeO)2C6H3
n-Bu
Ph
Ph
TMSOTf (1 eq)
TMSOTf (1 eq)
Acid
CO2Me
0°
0°
0°
0°
0°
0°
0°
0°
rt
rt
(72)
(66)
(82)
(84)
(65)
(64)
(87)
(87)
(0)
(66)
(83)
I
R2
I + II
OH
rt
R
1
Temp
PhMe2SiH (1.1-1.2 eq), acid
R2
R2
Ph
O
Conditions
I:II
R1
93:7
98:2
47:53
>99:1
71:29
70:30
>99:1
>99:1
—
78:22
79:21
+
OH
II
R2
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
R1
1
Ketone
276
Refs.
419
C12
O
Ph
Ph
HO
O
OBz
O
O
O
Ph
TBAF (5-10 mol%), HMPA, 0°, 4 h
PhMe2SiH (1.1-1.2 eq),
CH2Cl2:DMF (4:1), 0°, 12 h
Cl3SiH (1.5 eq),
MeC6H5, 0°, 1 h
Et3SiH, B(C6F5)3 (2 mol%),
CH2Cl2, 0°, 2 h
Ph2MeSiH (2 eq), TMSOTf (1 eq),
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
Ph3CH (0.1 eq), CH2Cl2, rt, 2 h
TMSH (xs), 220-TFPB (0.09 eq),
I
+
(79)
Ph
OBz
OH
+ II
OH
(85)
I + II (98), I:II = 1:1.5
Ph
(13)
I + II (76), I:II = 33:67
I
OH
Ph
Ph
OH
O
OH
OBz
II
OH
(91) cis:trans = 40:60
320
318
372
336
367
424
420
C12
t-Bu
Ph
O
HO
HO
O
O
N
O
O
H
O N
NHCO2Et
Ph
H
Ketone
O
O
TASF (10 mol %), DMPU, 0°, 16 h
PhMe2SiH (1.2 eq),
PhMe2SiH (1.2 eq), TFA, 0°, 2.5 h
PMe3 (60 mol%), MeC6H5, –20°
Ph2SiH2, Cp2Ti(PMe3)2 (10 mol%),
Et3SiH (3.2 eq), TFA, rt, 24 h
Et3SiH (3.2 eq), TFA, 0°, 1 h
Conditions
I
H
t-Bu
Ph
HO
OH
OH
Ph I
N
H
OH +
HO
Ph II
N
II
OH
H
III
N
Ph
O
I
O N
+ t-Bu
OH
II
O N
(87) threo:erythro > 99:1
I + II (90), I:II = 91:9
NHCO2Et
I + II + III (75), (I + II):III = 99:1, I:II = 1:1
+
+
HO
I + II (56), I:II = 1:4
O
I + II (77), I:II = 4:1
HO
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
H
OH
320
86
428, 249
394
394
Refs.
421
C12-13
Cl
MeO
MeO
EtO2C
Ph
MeO
Ph
O
O
O
O
O
O
O OEt
NHCOCF3
O
O
n
CO2H
NHCO2Me
NHCOCF3
2. Et3SiH, TiCl4, CH2Cl2, 0°, rt
1. TMSCl, Et3N
TFA, reflux, 2 h, rt, 16 h
Et3SiH (3.42 eq),
CH2Cl2, rt, 10 h
Et3SiH (2.6 eq), BF3•OH2 (4-6 eq),
CH2Cl2, rt, 5-20 min
PMHS (3 eq), (C6F5)3B (5 mol%),
CH2Cl2, rt, 5-20 min
PMHS (3 eq), (C6F5)3B (5 mol%),
CH2Cl2, 20°, 18 h; 40°, 4 h
Ph2SiH2 (1.2 eq), AlCl3 (1 eq),
reflux, 2 h; rt, 16 h
Et3SiH (3.42 eq), TFA,
Cl
MeO
MeO
EtO2C
Ph
MeO
Ph
OH
O
OH
(70)
OEt
n
(82)
CO2H
+ Ph2HSiCl (—)
n = 2 (85)
n = 1 (89)
(74)
(78)
(88)
NHCOCF3
O
(72)
NHCO2Me
NHCOCF3
421, 752
376
217
354
354
373
376
422
C12-15
C12-14
Cl
Fe
Solvent none none none none CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2
TFA TFA BF3•OEt2 BF3•OEt2 TiCl4 TiCl4 TiCl4 AlCl3 SnCl4
Me
H
Me
H
Me
TMS
TMS
TMS
Et3SiH, acid, solvent
Acid
CO2R
NHCO2Me
H
O
rt
rt
rt
rt
rt
rt
70°
reflux
reflux
Temp
Et3SiH (2.5 eq), TFA (5 eq), 20°
Conditions
Cl
Cl
+
Fe
(85)
I
(—)
(45)
(88)
(25)
(67)
(12)
(—)
(25)
(—)
(—)
(—)
(38)
(—)
(—)
(—)
(—)
(—)
II
IV
O
II: X = Cl
Cl
(—)
(23)
(—)
(—)
(—)
(28)
(—)
(—)
(—)
III
O
(—)
(—)
(—)
(—)
(—)
(—)
(65)
(49)
(54)
IV
Cl
+
NHCO2Me
CO2R
+
(65)
CO2Me CN NHCO2Me
(45)
(40)
Cl
H
I: X = H
X
(—)
X
X
(—)
(—)
(—)
(—)
(—)
(—)
(6)
(10)
(7)
V
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
R
X
O
Ketone
V
O
III
O
NHCO2Me
CO2R
NHCO2Me 421
180
Refs.
423
C12-18
R
O
(87) (81) (80) (80) (75) (82) (78) (67)
2 3.0 2 2.67 3.0 2.5 3.0 2.07
2.33 2.67 2.33 2.67 2.5 2.5 2.6 2.4
n-Pr
i-Pr
n-Bu
n-C6H13
c-C6H11
Ph
4-MeC6H4
4-BrC6H4
(84) (90) (73) (75) (80) (81) (81) (52) (87) (70) (84)
1.1 1.06 1.07 1.07 1.0 1.02 1.02 1.02 1.37 1.02 1.02
Me
Et
n-Pr
i-Pr
n-Bu
n-C6H13
c-C6H11
Ph
4-MeC6H4
4-BrC6H4
CCo3(CO)9
Me
x
R
OH
(92)
2
2.33
Et
Et3SiH (x eq), CO, C6H6, reflux, 8 h
(90)
y 2.07
x
CCo3(CO)9
2.4
R
R
Me
THF, reflux, 6 h
Et3SiH (x eq), TFA (y eq),
R
CCo3(CO)9
310
310, 425
424
O
R2 Me i-Pr i-Pr i-Pr i-Pr i-Pr n-Bu
Me
i-Pr
i-Pr
i-Pr
i-Pr
n-Bu
O
i-Pr
O
R2
C6H13-n
R1
H
O
CO2Et
R1
(i-Pr)2Si
EtO2C
n-C6H13
C13-17
C13
Ketone
x
0.1 0.1 0.5 0.5
TiCl4 BF3•OEt2 SnCl4
MgBr2•OEt2 0.1
0.1
SnCl4
0.1
SnCl4
SnCl4
Catalyst
Catalyst (x eq), CH2Cl2
SnCl4 (0.1 eq), –80°, 2 h
24 h
2h
2h
2h
Time
–80°
–80°
2h
2h
–80° 30 min
rt
–80°
–80°
–80°
Temp
PMe3 (60 mol%), MeC6H5, –20°
Ph2SiH2, Cp2Ti(PMe3)2 (10 mol%),
MeC6H5, –20°
Ph2SiH2 (1.0 eq), Cp2Ti(PPh3)2,
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
Conditions
CO2Et I
EtO2C CO2Et II
HO
(43)
O
I + II
R1
I
(44)
(—)
(—)
(—)
(67)
(68)
(61)
I + II
O Si (Pr-i)2
R2
+ EtO2C III
CO2Et
HO
+ O
40:1
320:1
30:1
60:1
120:1
40:1
50:1
I:II
R1
II
O Si (Pr-i)2
R2
(69) 40:1
i-Pr
(67) 50:1
I + II I:II Me
R2 i-Pr Me
R1
I + II (68), I + II:III = 99:1, I:II = 10:1
+
C6H13-n
I (65), I + II:III = 9:1, I:II 99:1
EtO2C
HO
n-C6H13
OH
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
398
399
429
428
367
Refs.
425
O
O
OH
O
Ph
O
O
HO
Ph
Ph
Ph
O
II (59) (50) (63) (55)
–5° 0° 21° 50°
+
(63)
I
Ph
Ph
–20°
OH
I (85)
I (83)
I (90)
I (85)
O I
OTBS
Temp
Cp2Ti(PPh3)2, MeC6H5
Ph2SiH2 (1.0 eq),
CH2Cl2, 0°, 2 h
Ph2MeSiH (2 eq), TMSOTf (1 eq),
CH2Cl2, 0°, 2 h
Ph2MeSiH (2 eq), TMSOTf (1 eq),
CH2Cl2, 0°, 15 min
Et3SiH (10 eq), TMSOTf (1 eq),
CH2Cl2, 0°, 2 h
Ph2MeSiH (2 eq), TMSOTf (1 eq),
CH2Cl2, 0°, 15 min
Et3SiH (10 eq), TMSOTf (1 eq),
Et2O, rt, 99:1
N
C8H17-n
O
+
OH
I + II (86), I:II = 99:1
NEt2
I + II (99), I:II < 1:99
Ar
OH
Ph
OH
I + II (98), I:II > 99:1
N
I + II (99), I:II < 1:99
Ph
OH
+
I + II (98), I:II > 99:1
NEt2
I + II (98), I:II < 1:99
Ph
OH
II
O
II
O
II
O
II
O
I + II (45), (I + II):III = 8.5:1, I:II:III = 4:1.6:1
N
Ar = 4-ClC6H4
Ar = 4-ClC6H4
NEt2
N
NEt2
423
320
87, 276
87
87, 276
87, 320
87, 276
87, 320
428
432
C14
MeO
MeO
MeO
MeO
Ph
Ph
Ph
Ph
O
MeO
(75)
(78)
(85)
NHCOCF3
(22)
(100)
Cl
(83)
NHCOCF3
CO2Et
Ph
OSiEt3
Ph
(90)
OH
MeO
MeO
MeO
O
O
CO2Me Et3SiH (3.0 eq), TFA, 0° to rt, 16 h
reflux, 2 h; rt, 16 h
Et3SiH (4 eq), BF3•OEt2 (20 eq),
Ph
Ph
Et3SiO
O
Ph
Product(s) and Yield(s) (%)
OH
NHCOCF3
rt, 48 h
Et3SiH (3.66 eq), BF3•OEt2 (20 eq),
C6H14, 70°, 4 h
Et3SiH (2.5 eq), (Ph3P)3RhCl (0.5 mol%),
Et3SiH (2.2 eq), TFA, rt
CH2Cl2, rt, 5-20 min
PMHS (3 eq), (C6F5)3B (5 mol%),
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1. SbCl5, TMSCl, SnI2,
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
CO2Me
O
Cl
OTMS
NHCOCF3
CO2Et
O
O
O
O
O
HO2C
Ph
O
Ketone
416
753
753
411
73
354
306
Refs.
433
C15
i-Pr
Fe
Fe
H
Ph
O
O
O
O
O
OEt
H
(i-Pr)2Si
O
N
O
O
Pr-i
I
Fe
Fe
Fe
O
O
H
I
O Si (i-Pr)2
OEt
H
(86)
(80)
+
OEt
H
II
N
i-Pr
H OH
Ph
I + II (—), I:II = 35:1 I + II (—), I:II = 2:1 I + II (—), I:II = 5:1
TFA (0.2 eq), –80°, 30 min TBAF (0.2 eq), –80°, 30 min (Ph3P)3RhCl (0.08 eq), C6H6, reflux, 12 h
I + II (—), I:II = 2:1 I + II (—), I:II = 1:2.5
ZnCl2 (0.25 eq), –80°, 30 min; rt, 15 min
BF3•OEt2 (0.5 eq), –80°, 2 h ZnBr2 (0.12 eq), –80°, 8 h; rt, 16 h
I + II (—), I:II = 30:1 I + II (—), I:II = 320:1
TiCl4 (0.5 eq), –80°, 30 min
O Si (i-Pr)2 II
Pr-i
I+II = (—), I:II = 38:62
O I + II (—), I:II = 60:1
Pr-i
O
(55)
+
I + II (—), I:II = 60:1
i-Pr
O
N
MgBr2•OEt2 (0.1 eq), rt, 24 h
SnCl4 (0.1 eq), –80°, 2 h
Et3SiH (4 eq), TFA, rt, 4 h
Et3SiH (20 eq), TFA, rt, 20 h
Et3SiH (2 eq), TFA, rt, 120 h
Et3SiH, TFA
OH
Ph
399
179
179
179
754
434
C15
O
O
MeO
Ph
Ph
O
O
Ph
O
OSiMe2H
Ph
OSiMe2H
OMe
OTMS
OTMS
Ketone
DCE, reflux, 10 h
Et3SiH (5 eq), CF3SO3H (1 eq),
DCE, reflux, 20 h
Et3SiH (5 eq), Sn-mont,
Et3SiH (2.5 eq), TFA (5 eq), 20°
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1. TrSbCl6 (5-30 mol%),
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1. SbCl5, TMSCl, SnI2,
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1. TrSbCl6 (5-30 mol%),
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1. SbCl5, TMSCl, SnI2,
DMF, 100°, 24 h
DMF, 100°, 24 h
Conditions
I (54)
I (75)
MeO
I (96)
Ph
I (77)
I
O
I
OH
OH
I
O
Ph
OH
OH
Ph
Ph
I
+
II
(92)
OH
OMe
OH
(68)
(67)
Ph
(10)
I + II (26), I:II = 1:4
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
353
353
180
306
306
306
306
400
400
Refs.
435
C15
C15-16
Ph
Ph
Ph
Ph
O
O
O
MeO
MeO
Ph
MeO2C
O
Ph
O
O
O
Ph
TMS
TMS
CF3
N
OR
O
Ph
O
MeC6H5, 0°, 1 h
Et3SiH, (C6F5)3B (2 mol%),
MeC6H5, 0°, 1 h
Et3SiH, (C6F5)3B (2 mol%),
TASF (5-10 mol%), HMPA
PhMe2SiH (1.1-1.2 eq),
TBAF (5-10 mol%), HMPA, 0°
PhMe2SiH (1.2 eq),
reflux, 2 h, rt, 16 h
Et3SiH (4 eq), BF3•OEt2 (20 eq),
CH2Cl2, rt, 5-20 min
PMHS (3 eq), (C6F5)3B (5 mol%),
TFA, 0°, 10 min, rt, 3 h
Et3SiH (2.6 eq), PPHF,
Et3SiH , TFA, CH2Cl2
Ph
Ph
Ph
Ph
I
OH
OH
I
OH
MeO
MeO
Ph
MeO2C
+
OR
CF3
N
Ph
(88)
I
+
II
OH
THP
Ph
Ph
Ph
OH
I + II (100), I:II = 6.5:1
TMS
+
II
OH
16 h (77)
12 h (95)
Time
I + II (100), I:II = 1:1
TMS
(88)
(96)
t-Bu
R
(98)
I + II (90), I:II = 93:7
Ph
OH
O
Ph
Ph
II
TMS
87:13
95:5
TMS
threo:erythro
372
372
320
86
376
354
135
415
436
C16
C15
O
Ph
O
O
O
H
H
O
PMP
PMP
Ph
Ph
O
O
O
O
N
HO O
NEt2
H
N
O
O
OPh
NHSO2Ph
H
H
Ketone
O
PMP
N
N
87, 320
320
CH2Cl2, 0°, 10 min
Ph2MeSiH (10 eq), TMSOTf (1 eq),
CH2Cl2, 0°, 10 min
Et3SiH (10 eq), TMSOTf (1 eq), H
H
H I I (88) trans:cis 4:1
O
O
O
H
H
O (75) trans:cis = 3:1
I + II (93), I:II < 1:99
336
336
375
II
O
II
O
87
II (90) H
Ph
OH
II
NEt2
Et3SiH (1.1 eq), TFA, 0°, 4 h
+
I + II (92), I:II = 99:1
N
+
OH
O
373
87, 276
N
PMP
OH
+ Ph2SiHCl (—)
I + II (92), I:II > 99:1
NEt2
+
(77)
86
I + II (90), I:II = 99:1
O
O
O
OPh
(66) threo:erythro = 2:98
PhMe2SiH (1.2 eq), TASF, 0°
I
I
O
NHSO2Ph
Refs.
Ph
OH
PMP
OH
I
OH
OH
PMP
Ph
Ph
OH
Product(s) and Yield(s) (%)
PhMe2SiH (1.2 eq), TFA, 0°, 5 h
DMPU, 0°, 16 h
PhMe2SiH (1.2 eq), TASF (10 mol%),
DMPU, 0°, 16 h
PhMe2SiH (1.2 eq), TASF (10 mol%),
CH2Cl2, 20°, 24 h
Ph2SiH2 (1.2 eq), AlCl3 (1 eq),
PhMe2SiH (1.1-1.2 eq), TFA, 0°, 20 h
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
437
C17
Bn
O
Ph
O O
O
O
O
Ph
OBz
Mn(CO)3
Fe
O
CN
CN
OTMS
CF3
CH2Cl2, rt, 45 min
Et3SiH (8 eq), TMSOTf (1 eq),
PhMe2SiH (1.2 eq), TFA, 0°, 6 h
HMPA, 0°, 12 h
PhMe2SiH (1.2 eq), TBAF (5-10 mol%),
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1. TrSbCl6 (5-30 mol%),
2. Et3SiH (1.5 eq), –23°, 2.5 h
CH2Cl2, –78°, 30 min
1. SbCl5, TMSCl, SnI2,
Et3SiH, TFA, CHCl3, 50-60°, 15 h
Et3SiH (6 eq), TFA, rt, 5 h
Ph
O
OH
I
O
OH
I (95)
Bn
Ph
OH
Ph
OH
OBz
Mn(CO)3
Fe CN
CN
(98)
(72) threo:erythro = 7:93
(82) threo:erythro = 96:4
(80)
CF3
(95)
(41)
339
86
86
306
306
351
179
438
C18
C17
Ph
Ph
H
O
O
O
O
O
OMe
OMe
H
O
Ph
OSiMe2H
Ph
HO
Bu-n
OSiMe2H
OMe
CO2H O
O
H
H
(i-Pr)2Si
n-Bu
Ketone
O
THF, –78°, 3.5 h
BnOSiMe2H, TBAF (6 mol%),
TBAF (6 mol%), THF, –78°, 3.5 h
I
Ph
+
OH
I (0)
BnOSiMe2H, TBAF (6 mol%),
OH Ph
THF, –78°, 3.5 h
H
H
O
O
I
OH
Ph
OH
I
Bu-n +
n-Bu O
O
II
OH
Ph
Ph
OMe
OMe
H
H
OH Ph
(88)
(76)
(80)
O
I + II (46), I:II = 13:87
(81) trans:cis = 3:1
II
O Si (i-Pr)2
Bu-n
Product(s) and Yield(s) (%)
I + II (60), I:II = 40:1
O Si (i-Pr)2
OMe
I
CO2H
O
n-Bu
TBAF (6 mol%), THF, –78°, 3.5 h
Et3SiH, TFA
CH2Cl2, 0°, 2 h
Ph2MeSiH (2 eq), TMSOTf (1 eq),
SnCl4 (0.1 eq), –80°, 2 h
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
400
400
400
400
417
336
399
Refs.
439
C19
C19-23
C18-23
C18-22
C18-19
Ar
S
(67)
O
Ar = 3-CF3C6H4
O
Et3SiH (5.1 eq), TFA, rt, 48 h
Et3SiH (2.5 eq), TFA, CH2Cl2, rt, 40 h
Ar
O
O
MeO
(58)
n-C5H11
Et3SiH (3 eq), TFA (5 eq), 6 h
(74)
n-Bu
R = Me, n-Pr, n-C5H11
(78)
i-Pr
(76)
(81) (78)
I
n-Pr
CH2Cl2, 0°, 30 min
I (70-90)
Et
Et3SiH (8 eq), TFA (10 eq),
Et3SiH (3 eq), TFA (5 eq), 50°, 6 h
Me
R
Et3SiH (8 eq), TFA (10 eq), 50°
H
R
HO2C
MeO
O
R = H, Et, n-Bu
O
O
O
O
O
O
(22)
I
(87)
H
OH
+
MeO
S
R
R
(11)
H
H
2h
(70-90)
OMe
6h
H
OH
(57)
(62)
(78)
6h
Br
(57)
24 h
Cl
Time
F
R
S
402
696
755
756
755
418
440
C20
C19-26
MeO
MeO
MeO
HO
TBSO
Bn
H
H O
H
H
O
H
H
H
H O
H
H
O
O OH
H
H
CH2Cl2, 0°, 2 h
Ph2MeSiH (2 eq), TMSOTf (1 eq),
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
MeO
MeO
MeO
O H
(93)
BzOCH2
HO
(97)
Ph
i-PrOH, DCE, O2, rt
(96)
Br(CH2)6
O
H
H
H
(91)
>99:1
(97)
EtO2CCH2
BnOCH2
>99:1
H
H
H
H
O
OH
>99:1 OH
>99:1
>99:1
>99:1
>99:1
>99:1
(95)
>99:1
I:II
Bn
H2C=CHCH2
H
+
(82)
I + II
R
HOCH2
I
O
(95)
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
Bn
(90)
O
MeCN, rt
Et3SiH (1.2 eq), BiBr3 (5 mol%),
H
H
II
O
O
(61)
(47)
R
(75) trans:cis = 3:1
Product(s) and Yield(s) (%)
i-Pr
R
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
Me
R
O
Ketone
336
367
367
342
Refs.
441
C21
C20-23
Ph
O
Ph
Fe
O
N
O
O
O
O
O
O
O Ph
O
N
Me
O
Ph
C9H19-n
N
O R O
(CO)9Co3C
Ph
O
2. HCl, acetone
18-C-6 (5 mol%), CH2Cl2, rt
1. PhMe2SiH (4 eq), CsF (5 mol%),
Et3SiH (20 eq), TFA, rt, 240 h
Et3SiH (6 eq), TFA (20 eq), 20°
Et3SiH, TFA
PhMe2SiH (1.2 eq), TFA, 0°, 4 h
I
Ph
HO
Ph
Fe
O
N
O
N
+
Ph
OH
Me
Ph
II (25) (20) (30) (20)
I (41) (47) (43) (43)
Me Et n-Pr n-Bu
(40)
(73)
O
II
R
+
(88)
I + II (98), I:II < 1:99
OH HO I
O
O Ph
O
C9H19-n
N
O R O
(CO)9Co3C
Ph
OH
O
O R
N
II
O Ph
O
369
179
757
183
87, 276
442
C21
O
O
O
O
H
H
N
H H
H
H
O
H
H
H
CO2Me
CO2Me
PMP
Ph
O
Ketone
O
Ph2SiH2, Rh-(–)-diop, C6H6, 22°
Ph2SiH2, Rh-(+)-diop, C6H6, 22°
Ph2SiH2, Rh-(–)-diop, C6H6, 22°
Ph2SiH2, Rh-(+)-diop, C6H6, 22°
2. Et3SiH, CH2Cl2
1. TFA, 2 h
H
H
H
H I
I
H
H
H +
OH
+
HO
+
OH
(17)
N
H
II
H
H
H
II
I + II (—), I:II = 67:33
H
I CO2Me
I + II (—), I:II = 64:36
HO
I:II = 7:3
I (25)
H
CO2Me
I + II (90), I:II = 1:1
Et3SiH, TFA, CH2Cl2, rt, 16 h
+
OH H H
PMP O I + II (50), I:II = 1:4
PhMe2SiH, TFA, THF, 0°, 22 h
I
N
Ph
I + II (90), I:II = 1:8
O
OH H H
H
(18)
OH
I:II 7:3
OH
H
CO2Me
H
II
H
H
Ph
CO2Me
PMP
Product(s) and Yield(s) (%)
PhMe2SiH, TASF, THF, HMPA, rt, 23 h
PhMe2SiH, TASF, THF, rt, 70 h
Conditions
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
573
573
573
573
758
758
371
371
371
Refs.
443
C24-26
C24
C23
Bn
S H
O
O
O
O
OTBS
S
O
Ph
Ph
O
O
O
Ph
O
R
R
Ph Bn
(30)
(33) Et Ph
R (49)
R
Me
R
H
O
Ph
R = H, Me, Et (—)
Ph
CCl4, 50-55°, 8 h
O
O
O
I + II (99), I:II > 99:1
O II
(73)
Et3SiH (5 eq), TFA (10 eq),
Et3SiH (6 eq), TFA (20 eq), 50°, 6 h
MeCN, rt
Et3SiH (1.2 eq), HBr (15 mol%),
MeCN, rt
+
OH
I + II (97) I:II > 99:1 I + II (99), I:II > 99:1
O I
H
Et3SiH (1.2 eq), TMSBr (15 mol%),
S
MeCN, rt
S
Bn
Et3SiH (1.2 eq), BiBr3 (5 mol%),
2. KOH, MeOH, THF, rt
CH2Cl2, 50°, 20 h
1. Et3SiH (10 eq), TFA (50 eq),
O
266
757
342
342
342
368
444
C31
C28
C27
O
O
HO
n-C10H21
O
O
H
C8H17-n
OPMP
CH(PMP)2
OBn
O TBSO
N
H
H
Ketone
2. TBSOTf, 2,6-lutidine, 0°
1. t-BuMe2SiH, BiBr3, MeCN, 0°
MeOC6H5, –25°, 1.5 h
BF3•OEt2 (0.23 eq),
Et3SiH (3 eq), TFA (4 eq),
i-PrOH, DCE, O2, rt
PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),
CH2Cl2, rt, 5-20 min
PMHS (3 eq), (C6F5)3B (5 mol%),
Conditions
I
n-C10H21
TBSO
O
OH
HO
O
OH
III
N
CH(PMP)2
OBn
H
H
O
OBn +
+
OH
(92)
II
O OPMP
(93)
OBn
O IV
N H
CH(PMP)2 OH
N
I + II (71), I:II = 8:1, III + IV (10)
N
H
H
C8H17-n
(—)
Product(s) and Yield(s) (%)
TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)
OBn
404
395
367
354
Refs.
445
C38
C37
H
O
O
H
O
HO H H
H
HO H
O
O
O
c This
CH2Cl2, 0°, 2 h
TMSOTf (1 eq),
Ph2MeSiH (2 eq),
CH2Cl2, 0°, 2 h
TMSOTf (1 eq),
Ph2MeSiH (2 eq),
column gives the amount of acid used in a one mmol reaction.
The yield was determined by gas chromatography.
H
O
H
H
The yield was determined by NMR spectroscopy.
O
H
O
b
H
H
H
O
H
a
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
H
H
H
O
O
H
H
O H
O H
O
H
H
O
O
(62) trans:cis = 6:1)
H
H
(55) trans:cis = 3:1
H
H
H
H
H
O
O
336
336
446
C5
C5-13
H Me Ph
Me
Ph
H
NH2
H
n-C7H15
t-BuO
H
Ph
O
H
Ph
Me
Bn
H
Me
H
H
—(CH2)6—
4-MeC6H4
Me
—(CH2)5—
—(CH2)2O(CH2)2—
Me
—(CH2)4—
Me
Me
—(CH2)2O(CH2)2—
R3
—(CH2)3—
H
—(CH2)5—
R2
H
R2
—(CH2)4—
R3
N
H
R1
R1
O
Amide
none none
Os3(CO)12 Ru3(CO)12
(92) (81)
t-BuO
O
(93.2)
(99.5)
(99.5)
(56.0)
(97.1)
(50.3)
(95.9)
(99.2)
(92.3)
(86.6)
(87.7)
(87.0)
(86.1)
NHBn
R2
(92.9)
R3
N
3
none
Et2NH
Et2NH
Et2NH
Et2NH
Et2NH
none
none
none
none
none
none
none
none
Cat-3
R1
0.33
x
PhCHO (x eq), MeCN, 22°, 18 h
Et3SiH (3 eq), TFA (2-3 eq),
EtI
none
EtI
EtI
none
none
EtI
none
none
EtI
[RuCl2(CO)3]2
Os3(CO)12
[RuCl2(CO)3]2
[RuCl2(CO)3]2
Ru3(CO)12
Ru3(CO)12
(Ph3P)2RuCl2(CO)2
Ru3(CO)12
Ru3(CO)12
(Ph3P)2RuCl2(CO)2
EtI
EtI
(Ph3P)2RuCl2(CO)2 (Ph3P)2RuCl2(CO)2
Cat-2
Cat-1
MeC6H5, 100°
cat-2 (5 mol%), cat-3 (5 mol%),
Et3SiH (3-3.5 eq), cat-1 (1 mol%),
Conditions
Product(s) and Yield(s) (%)
TABLE 13. ORGANOSILANE REDUCTION OF AMIDES
326
432
Refs.
447
C7
O
N
none none none none
IrCl3 K2IrCl6 Pd(OH)2/C PtCl2
none Et2NH
(Ph3P)2RuCl2(CO)2 EtI EtI none
[RuCl2(CO)3]2 Os3(CO)12
t-BuMe2Si i-Pr3Si ClMe2Si
[RuCl2(CO)3]2
EtI
Et2NH
none
Me(EtO)2Si (Ph3P)2RuCl2(CO)2 EtI (EtO)3Si
none
Me2(EtO)Si (Ph3P)2RuCl2(CO)2 EtI
Et2NH
none
Cat-3
16 h
16 h
16 h
16 h
40 h
16 h
16 h
Time
(78.5)
(77.7)
(92.6)
(94.4)
(99.5)
(Ph3P)2RuCl2(CO)2 EtI
Cat-2
I
16 h
40 h
16 h
16 h
(99.3)
PhMe2Si
MeC6H5, 100° Cat-1 R3Si
cat-2 (5 mol%), cat-3 (5 mol%),
R3SiH (3-3.5 eq), cat-1 (1 mol%),
Et2NH
Et2NH
Et2NH
none
16 h
Et2NH
none
(99.8)
(Ph3P)4RhH
16 h
none
Os3(CO)12
pyridine
(88.0)
none
Os3(CO)12 16 h
(94.4)
16 h
Et2NH
EtI
Ru(acac)3 Et2NH
(94.1)
40 h
Et2NH
EtI
(Ph3P)3RuH2(CO)
(98.1)
16 h
none
(Ph3P)2RuCl2(CO)2 I2
(96.1)
16 h
none
16 h
none
none
Ru3(CO)12 (Ph3P)2RuCl2(CO)2 MeI
(88.2)
16 h
Et2NH
none
Re2(CO)10 none
16 h
Et2NH
none
(Ph3P)2RuCl2(CO)2 EtI
(95.6)
16 h
Cat-3
Cat-2 (89.3)
I
Mn2(CO)10
Time
N
Cat-1
MeC6H5, 100°
cat-2 (5 mol%), cat-3 (5 mol%),
Et3SiH (3-3.5 eq), cat-1 (1 mol%),
I
(86.1)
(90.8)
(93.1)
(80.1)
(50.6)
(70.4)
(90.2)
432
432
448
C8
C7
C7-8
O
MeCN MeC6H5 MeC6H5 MeC6H5 MeCN
PhO
PhNH
Bn
4-MeOC6H4
BnO
O NH2
N Bu-n
O
MeC6H5
4-FC6H4
22°
22°
120°
120°
22°
22°
120°
120°
18 h
18 h
18 h
36 h
18 h
18 h
18 h
18 h
Temp Time
THF, rt, 3.5 h
(Ph3P)3RhH(CO) (1 mol%),
Ph2SiH2 (4.3 eq),
THF, rt, 0.5 h
(Ph3P)3RhH(CO) (0.1 mol%),
Ph2SiH2 (2.1 eq),
MeCN, 22°, 18 h
EtCH(OEt)2 (0.33 eq),
Et3SiH (3 eq), TFA (2.9 eq),
MeC6H5
MeC6H5
BnNH
Solvent
Ph
PhCHO (x eq)
Et3SiH (3 eq), TFA (2-3 eq),
Conditions
N H
Ph
N Bu-n
N Bu-n
O N H
(89)
(95)
(95)
(92)
(92)
(90)
(92)
(91)
(70)
(88)
(92)
(91)
(68)
(97)
(85)
(93)
(94)
x = 0.33 x = 3
Ph
R
O
(66)
(65)
Product(s) and Yield(s) (%)
TABLE 13. ORGANOSILANE REDUCTION OF AMIDES (Continued)
R
NH2
O N Bu-n
Ph
R
O
Amide
431
431
326
326
Refs.
449
C9-14
R2 Me Me Et Et Et Et Et Et Et Ph
Me
Me
Et
Et
Et
Et
Et
Et
Et
Me
R2
N
R1
R3
O R1
(88) (93) (90) (91) (96) (94) (77)
Cp2TiMe2 Cp2TiF2 Cp2TiMe2 Cp2TiF2 Cp2TiMe2 Cp2TiF2 Cp2TiF2 Cp2TiMe2 Cp2TiF2
H H H 4-Cl 4-Cl 4-Me 4-CF3 4-MeO H 50:50
56:44
53:47
62:38
53:47
53:47
53:47
52:48
52:48
52:48
(80)
Cp2TiF2 (92)
meso:rac (84)
Catalyst
I
NR1R2
H
R3
R1R2N
R3
MeC6H5, 80°, 1 h
PhMeSiH2 (2 eq), catalyst (1 mol%), R3
430
450
C10
C9-14
Et Et Et Et Ph
Et
Et
Et
Et
Me
N
Et
Et
R1
NEt2
R2 Me
R1
O
N R2
Me
R3
O
(100) (100) (55.9) (14.7)
4-MeO 4-Me 4-CF3 H
MeC6H5, 20°, 30 min
2. PhMeSiH2 (2 mmol), amide (1 mmol),
MeC6H5, 70°, 10 min
Cp2TiF2 (0.1 mol),
1. PhMeSiH2 (3 mmol),
MeC6H5, 80°, 1 h
(44.8)
4-Cl
PhMeSiH2 (2 eq), Cp2TiF2 (1 mol%),
(97.7)
H
+ R3
R3
NEt2
55:45
53:47
50:50
53:47
53:47
60:40
54:46
meso:rac
NR1R2
II
N
(44.2)
(20.6)
(0)
(0)
(29.9)
(0)
(2.0)
R1 +
III
II
N
O
O
(25)
R3 III
NEt2
(41.1)
(23.5)
(0)
(0)
(25.3)
(2.3)
(16.7)
I (43.5) meso:rac = 56:44 + II (34.1) +
+
II
R2
N
Product(s) and Yield(s) (%)
I N N (27) meso:rac = 57:43
Et2N
I
I
(81.3)
R3
R1R2N
R3
MeC6H5, 20°, 30 min
2. PhMeSiH2 (2 mmol), amide (1 mmol),
MeC6H5, 70°, 10 min
Cp2TiF2 (0.1 mol),
1. PhMeSiH2 (3 mmol),
Conditions
TABLE 13. ORGANOSILANE REDUCTION OF AMIDES (Continued)
H
Amide
430
H (22.4) 430
H
430
Refs.
451
C11
C10-19
Ph
Ph
R
1
O
O
NBu2 NBu2 NEt2 NMe(C6H11-c) N(C6H11-c)2
i-Pr t-Bu 4-MeO2CC6H4 Ph Ph
NEt2
NMe2
48 h
NEt2
4-BrC6H4
O
24 h
NEt2
Ph
85:15:0 43:9:48 92:8:0 59:1:49
80° 20° 80°
[—(Me)(H)SiO—]4 80° 80°
n-C6H13SiH3 [—(Me)(H)SiO—]4 20° 20°
n-C6H13SiH3
PMHS PMHS
(—)
51:30:19
92:8:0 100:0:0
20°
PhSiH3
I:II:III
PhSiH3
I
Ph
+
NMe2
NEt2
NEt2
(83)
(91)
(70)
(86)
(90)
(85)
(85)
(98)
NR2
Temp
Ph
Et2N
Ph
Ph
R1
Silane
MeC6H5, 1 h
Silane (1 eq), Cp2TiF2 (0.1 mol),
2. Acid, 0.5 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (2.5 eq), 2 (1 mol%),
2. Add acid, 0.5 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (2.5 eq), 2 (1 mol%),
48 h
4h
4.5 h
20 h
2h
3h
N(CH2)5
Time
NR2
MeO2CCH2CH2
(Ph3P)3RhH(CO) (0.1 mol%), THF, rt
Ph2SiH2 (2.1 eq),
R1
NR2
II
NEt2
(—)
56:44
55:45
52:48
56:44
55:45
57:43
54:46
I meso:rac
Ph
(56)
(75)
Ph
(0)
(37)
(81)
(40)
(90)
(66)
(83)
(86)
+
III
O H
430
280
280
431
452
C14
C12
C11
Br
Ph
O
S
8
O
8
O
8
O
O
NHBu-t
NEt2
O
O
NMe2
NMe2
O
N Bn
NEt2
NEt2
Amide
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
THF, rt, 3 h
(Ph3P)3RhH(CO) (0.1 mol%),
Ph2SiH2 (2.1 eq),
2. Add acid, 2 h
1,4-dioxane, 20°, 0.5 h
1. EtMe2SiH (2.5 eq), 225 (1 mol%),
Conditions
S
8
I
H
H
O
O
8
O
I (90)
Br
Ph
N Bn
H
H
(90)
O
O
(74)
NMe2
(45)
(65)
(80)
(65)
Product(s) and Yield(s) (%)
TABLE 13. ORGANOSILANE REDUCTION OF AMIDES (Continued)
433
433
433
433
433
431
280
Refs.
453
C16
C15
O
O
2-Np
O 8
8
O
NHBu-t
NHBu-t
NEt2
NBn2
O
Catalyst (Ph3P)3RhH(CO) (Ph3P)4RhH [Rh(cod)2]BF4 (Ph3P)3RhCl RhCl3•3H2O (Ph3P)3RhH(CO)
R3Si Ph2HSi Ph2HSi Ph2HSi Ph2HSi Ph2HSi Ph3Si
THF, rt
—
48 h
48 h
42 h
0.5 h
1h
Time
R3SiH (2.1 eq), catalyst (0.1 mol%),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
MeC6H5, 20°, 30 min
2. PhMeSiH2 (2 mmol), amide (1 mmol),
70°, 10 min
Cp2TiF2 (0.1 mol), MeC6H5,
1. PhMeSiH2 (3 mmol),
Cp2TiF2 (1 mol%), MeC6H5, 80°, 1 h
PhMeSiH2 (2 eq), Np-2
NEt2 + 2-Np
O
O
(0)
(95)
(93)
(86)
(93)
(94)
NBn2
8
8
O
H
H
(50)
(90)
O
(9)
2-Np
II
NEt2
I (51.2) meso:rac = 48:52 + II (39.6) +
I (83) meso:rac= 54:46
2-Np
Et2N
H
(9.2)
431
433
433
430
430
454
C20
C18
C17
C16
N
BnO
7
8
O
TBSO
8
O
NHBu-t
O 10
9
O
5
O
8
O NMe2
N(Pr-i)2
N(Pr-i)2
NHBu-t
NMePh
5
O
N(Pr-i)2
Amide
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Ti(OPr-i)4 (1.0 eq), 20°
Ph2SiH2 (1.1 eq),
Conditions
N
BnO
7
8
O
TBSO
8
O
O
O 10
9
O
5
O
H
5
H
H
H
H
O 8
H
H
(80)
(80)
(81)
(83)
(87)
(78)
(83)
Product(s) and Yield(s) (%)
TABLE 13. ORGANOSILANE REDUCTION OF AMIDES (Continued)
433
433
433
433
433
433
433
Refs.
455
C5
C4-12
C4
R
N
O
O
N H
H
H
O
CHO
Aldehyde/Ketone
N
N
N
Ar = 4-TBSOC6H4
Me2SiH(NEt2) (1.2 eq)
Ar
Ph
(CH2)3NMe2
Ph
NH2
3-C5H4N
2-C4H3S
Ph 4h
4h
4h
CH2Cl2, 0° to rt, 36 h
TiCl4 (0.20 eq),
TBAF, 20° or reflux, 24-300 h
(n-Bu)2SnCl2 (0.02 eq), THF,
PhSiH3 (1.1 eq),
THF, 20° or reflux, 24-300 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
4-FC6H4
Ph
CN
NH2
4h
Ph
2-C4H3S
CN
N
4h
Ph
4-MeOC6H4
CN
2h
Ph
n-Pr
CN
Time
R3
R
N H
Et3SiH (2 eq), TFA, CH2Cl2, rt
2
R3
SO2R2
Conditions
R1
R1
Amine
N
N
O
HO
R1
H N R
NEt2
(90)
(93)
(95)
(93)
(94)
(90)
HN
N
N
N
(56) n-C11H23
(57)
(10) n-C11H23
(17) Bn
(41)
(25) Ph
i-Pr
n-Pr
R
(50) Bn
R
(72) Ph
H N
(70)
(63) i-Pr
n-Pr
R
(65)
N
R3
SO2R
2
Product(s) and Yield(s) (%)
TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES
359
362
362
360
Refs.
456
C7
C6
O
Ph
O
c-C6H11
t-Bu
H
O
O H
O
Aldehyde/Ketone
PhNH2
BnNH2
Me2SiH(NEt2) (1.2 eq)
N H
PhNH2
BnNH2
MeCN
MeCN
Amine
2. PMHS (2 eq), THF, 5 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
2. PMHS (2 eq), THF, 5 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
0° to rt, 36 h
ZnI2 (0.10 eq), CH2Cl2,
2. PMHS (2 eq), THF, 5 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
2. PMHS (2 eq), THF, 4.5 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
2. PMHS (2 eq), THF, 4.5 h
THF, rt, 1 h
1. Ti(OPr-i )4, (1.25 eq),
H2O, 28°, 65 h
Et3SiH (1.1 eq), H2SO4,
H2O, 28°, 65 h
Et3SiH (1.1 eq), H2SO4,
Conditions
Ph
Ph
c-C6H11
N
HN
NHPh
NHBn
Ph
O
(92)
(90)
(81)
(85)
(87)
(88)
(78)
(67)
Product(s) and Yield(s) (%)
NEt2
H N
NHBn
N H
O
TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)
363
363
359
363
363
363
313
313
Refs.
457
C7-9
R
I
O
O2N
H
O H
O H
N
N
N
NH2
PMP
NH2
N Ar1 Ar1 = 4-TBSOC6 H4
BnNH2
PhNH2
PhNH2
BnNH2
PhNH2
Ar1
PMP
N H
N
N
H N
PMP
NH
Ph
0°, 4 h
(86)
(85)
(85)
(37)
(74) BnCH2
(93)
(E)-PhCH=CH (81)
c-C6H11
NHPh
NHPh
NHBn
(80)
R NHBn
NHPh
(78)
Ph
(85)
N Ar2 Ar2 = 4-HOC6H4
N
N
1. MgSO4, CH2Cl2, rt, 1 h R
I
O2N
O2N
Ph
Ar2
PMP
Ph
2. Cl3SiH, CH2Cl2/DMF (4:1),
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
2. PMHS (2 eq), THF, 4 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
THF, TBAF, 20°, 24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
THF, 20°, 24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
2. PMHS (2 eq), THF, 5.5 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
318
361
361
363
361
362
362
363
458
C7-10
R
1
R2 H H H H H Me H Me H H H H H Me H H Me
Ph
Ph
4-MeC6H4
4-MeC6H4
4-O2NC6H4
Ph
BnCH2
BnCH2
Ph
BnCH2
Ph
BnCH2
Ph
Ph
BnCH2
BnCH2
BnCH2
R
2
R1
O
Aldehyde/Ketone
R4
Me
Me
Me
Me
Me
Me
Me
Me
H
H
H
H
H
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
—(CH2)2O(CH2)2—
—(CH2)2O(CH2)2—
—(CH2)4—
—(CH2)4—
Me
Me
Me
Me
Me
Me
Me
Me
R3
R3R4NSiHMe2 (1.2 eq)
Amine
Ph3CClO4
Ph3CClO4
Ph3CClO4
Ph3CClO4
Ph3CClO4
ZnI2
TiCl4
ZnI2
TiCl4
TiCl4
ZnI2
TiCl4
TiCl4
TiCl4
TiCl4
(83) (66) (94)
36 h 2h
0.05
(86)
(71)
36 h
(88)
(77)
36 h
1h
(67)
36 h
0.05
(72)
48 h
(40)
(87)
36 h
1h
(94)
36 h
0.05
(85)
48 h
(53)
(67)
36 h
3h
(73)
36 h
0.05
(64)
36 h
R2
36 h
Time
R1
NR3R4
1h
0.05
0.1
0.2
0.1
0.3
0.2
0.1
0.4
0.2
0.4
0.2
0.4
TiCl4 TiCl4
x 0.2
Catalyst
Catalyst (x eq), CH2Cl2, 0° to rt
Conditions
Product(s) and Yield(s) (%)
TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)
359
Refs.
459
C7-13
R1
Me Me Me
Ph
Ph
Ph
H
(E)-PhCH=CH
Me
H
(E)-PhCH=CH
Ph
H
(E)-PhCH=CH
Me
H
(E)-PhCH=CH
Ph
H
Ph
Me
H
Ph
Ph
H
Ph
H
H
Ph
(E)-PhCH=CH
H
Ph
H
H
(E)-PhCH=CH
R2
Ph
R2
R1
O R NH2
3
Activator AlCl3 Pd-C Ti(OPr-i)4 AlCl3 Pd-C Ti(OPr-i)4 AlCl3 Pd-C Ti(OPr-i)4 AlCl3 Pd-C Ti(OPr-i)4 AlCl3 Pd-C Ti(OPr-i)4 AlCl3 Pd-C Ti(OPr-i)4
R3 Bn Bn Bn Ph Ph Ph Bn Bn Bn Ph Ph Ph Bn Bn Bn Ph Ph Ph THF
EtOH
MeC6H5
THF
EtOH
MeC6H5
THF
EtOH
MeC6H5
THF
EtOH
MeC6H5
THF
EtOH
MeC6H5
THF
EtOH
MeC6H5
6h
10 h
13 h
6h
10 h
13 h
4.5 h
9h
12 h
4h
8h
10 h
5h
10 h
12 h
5h
10 h
12 h
Solvent Time (2)
2. PMHS (2 eq), THF
solvent, rt, 1 h
1. Activator (1.25 eq), R1
(90)
(58)
(50)
(90)
(55)
(45)
(88)
(56)
(45)
(85)
(55)
(48)
(92)
(62)
(52)
(90)
(60)
(40)
R2
NHR3 363
460
C7-13
R1
Ar
(86)
H
4-PhC6H4
H Me H Ph
Ph
n-C7H15
Ph
—(CH2)5—
Ph
R1 R2
(46)
Ph
Ph
(85)
72 h 48 h
(63)
(0)
(80)
74 h 72 h
(30)
72 h
Time
N H
(84)
H
4-MeO2CC6H4
R2
(39)
Et
Ph
H2O, 28°
(84)
H
4-NCC6H4
R2
(92)
H
4-MeOC6H4
R1
(91)
H
4-MeC6H4
Et3SiH (1.1 eq), H2SO4,
(65)
Me
Ph
MeCN
(85)
H
4-O2NC6H4
O
(78)
H
(90)
H
R
4-ClC6H4
Ar
NEt2
R
CH2Cl2, 0° to rt, 36 h
TiCl4 (0.20 eq),
Conditions
Ph
R
Me2SiH(NEt2) (1.2 eq)
Amine
O
Product(s) and Yield(s) (%)
TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)
Ar
O
Aldehyde/Ketone
313
359
Refs.
461
C8
C7-23
PMP
Ar
O
1.1 1.1 1.1 1.1 1.1 0.5 0.33 0.20 2.0 1.1
Ph3Si Ph2HSi Ph2HSi PhH2Si PhH2Si PhH2Si PhH2Si PhH2Si PMHS PhH2Si
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
x 1.1
R3Si Et3Si
PhNH2 (1.0 eq), THF, rt, 21 h
PMP
(91)
NHMePh
(46)
4-TBDPSOC6H4
N H
(0) N Me
(82)
(—)
(83)
(83)
(83)
(82)
(—)
(88)
(0)
(0)
(90)
4-TBSOC6H4
(n-Bu)2SnCl2 (0.02 eq),
(75)
4-BnOC6H4
H
(96)
4-AcOC6H4
O
(91)
Ph
Ph
NHCOPh
4-HO2CC6H4
PMP
Ar
(96)
R3SiH (x eq),
MeC6H5, 120°, 18 h
Et3SiH (3 eq), TFA (2.9 eq),
4-MeO2CC6H4
PhNH2
PhCONH2 (3 eq)
4-FC6H4
Ar
H
(83)
361
361
326
462
C8
O
O
PMP
5
O
O
O H
Aldehyde/Ketone
PhNH2
PhNH2
Et2NH
N H
N H Ph N
O
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.1 eq),
PhSiH3 (1.1 eq),
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
THF, rt, 16 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
THF, rt, 16 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
THF, rt, 16 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
PhSiH3 (1.1 eq), THF, rt, 16 h
THF, rt, 16 h
(n-Bu)2SnCl2 (0.02 eq),
O
O
NHPh
PMP
PMP
PMP
I (13)
I
(70)
(49)
(67)
(78)
NHPh
NPh
O
(91)
NEt2
N
N
N
(85)
N H
(85)
PhSiH3 (1.1 eq),
(85)
Product(s) and Yield(s) (%) Ar
4-t-BuC6H4
N H (82)
PMP
PMP
4-O2NC6H4
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
Conditions
4-MeOC6H4
Ar
ArNH2
Amine
TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)
361
361
361
361
361
361
361
361
Refs.
463
C9
Ph
Ph
Ph
O
O
O
H
H
N H
BnNH2
PhNH2
Me2SiH(NEt2) (1.2 eq)
N H
BnNH2
PhNH2
PhNH2
2. PMHS (2 eq), THF, 4.5 h
THF, rt, 1 h
1. Ti(OPr-i)4 (1.25 eq),
2. PMHS (2 eq), THF, 4 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
2. PMHS (2 eq), THF, 4.5 h
THF, rt, 1 h
1. Ti(OPr-i)4 (1.25 eq),
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
0° to rt, 36 h
ZnI2 (0.10 eq), CH2Cl2,
2. PMHS (2 eq), THF, 6 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
2. PMHS (2 eq), THF, 6 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
2. PMHS (2 eq), THF, 6 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.1 eq),
PhSiH3 (1.1 eq),
I
N
Ph
Ph
I (88)
Ph
Ph
Ph
Ph
NHPh
I
NHBn
I (90)
Ph
N
NHBn
NHPh
NEt2
(88)
(90)
(70)
(85)
(85)
(70)
(72)
363
363
363
361
359
363
363
363
361
464
C13
C10
Ph
Ph
O
t-Bu
Ph
O
CO2Bu-t O
N
O
O
Aldehyde/Ketone
ArNH2
N H
Ph
(83)
Ph
NHAr
N
(88)
(80)
NEt2
NHBn
t-Bu
(85)
Ph
Ph
Ph
+
t-Bu
+
(46)
II
O
t-Bu
OH
I
+
Bu-t
t-Bu
(21)
I + II (70)
NHEt
Product(s) and Yield(s) (%)
(86)
(4)
CO2Bu-t
N
NHPh
Bn
2. PMHS (2 eq), THF, 4.5 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
2. PMHS (2 eq), THF, 4.5 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
0° to rt, 36 h
ZnI2 (0.10 eq), CH2Cl2,
2. PMHS (2 eq), THF, 4.5 h
THF, rt, 1 h
1. Ti(OPr-i )4 (1.25 eq),
H2O, 28°, 65 h
Et3SiH (1.1 eq), H2SO4,
THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq),
Conditions
Ph
Ar
Me2SiH(NEt2) (1.2 eq)
BnNH2
MeCN
PhNH2
Amine
TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)
363
363
359
363
313
361
Refs.
465
C14
H OBn
O PhNH2 THF, rt, 2-24 h
(n-Bu)2SnCl2 (0.02 eq),
PhSiH3 (1.1 eq), OBn
NHPh (82) 361
466
C9
C5
C4
C3
Ph
O
O
O
H
O
H
H
H
Unsaturated Aldehyde
Ph
(EtO)3SiH (1.1 eq), KF (1 eq),
(85) (65) (65) (100)
C6H4(CO2K)2-1,2 CsF
I
Ph2SiH2 (0.5 eq), salt Salt KF
I (95)
Me(EtO)2SiH (1.1 eq), CsF (1 eq), rt, 2 h
HCO2K
I (80)
(EtO)3SiH (1.1 eq), CsF (1 eq), rt, 1 h
rt, 24 h
I (98.6)
I (—)
I (—)
Ph
I
I
O
O
O
H
H
(9)
O
OH n-Pr
PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)
0° to rt, 2 h
Ph2SiH2 (1.1 eq), (Ph3P)3RhCl,
C6H6, 45°, 1 h
Et3SiH (1.1 eq), (Ph3P)3RhCl,
rt, 3 min
Ph2SiH2 (2.3 eq), CsF (1 eq),
PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)
PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)
CHCl3, 40°, 6 h
Et3SiH (3 eq), TFA (6 eq),
Conditions
OH
H
Pr-n
(100)
(100)
(100)
+
(10) +
(95)
(—)
O2CCF3 (—)
+ CF3CO2Pr-n
OH (12) +
Product(s) and Yield(s) (%)
TABLE 15. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ALDEHYDES
319
79, 83
79
79, 83
438
435
435
83
438
438
434
Refs.
467
C10
O
H
O
O
H
H
H
I
O + I + II
(Ph3P)4Pd (0.012 eq), CHCl3, rt, 1.5 h
Ph2SiH2 (2.0 eq), ZnCl2 (0.12 eq),
O H
H
0:100
Ph2SiH2 Et3SiD (1.1 eq), (Ph3P)3RhCl
(94) 3:97
Et2HSi
(96)
(100)
(97)
(95)
(97) 49:51
(92) 100:0
I:II
H
(i-Pr)2HSi
D O
(80)
(—)
(100)
Et3Si
O
OSiEt3
OSiMe2Ph
100:0
Ph
Ph
EtMe2Si
R3Si
R3SiH (1.1 eq), (Ph3P)3RhCl
MeC6H5, 5 h
PhSiH3 (1.5 eq), [(Ph3P)CuH]6 (5 mol%),
Et3SiH (0.72 eq), H2PtCl6
HMPA, rt, 0.5 h
PhMe2SiH (1.2 eq), TBAF (2 eq),
II
OH
436
435
435
447
76
320
76
Ph
Et3SiH (1.5 eq), CsF (1.5 eq), (—)
83
I (100)
(EtO)3SiH, CsF, rt, 5 min OSiEt3
83
I (95)
(EtO)3SiH (2.3 eq), KF (1 eq), rt, 24 h
MeCN, rt, 10 h
83
315
I (95)
I (69)
Me(EtO)2SiH (2.3 eq), CsF (1 eq), rt, 2 h
Et2O, rt, 24 h
PMHS (1 eq), ZnCl2 (1 eq),
468
C4
O
Unsaturated Ketone
H , Et2MeSiH,
1h 15 h 3h 3h
20° 20° 0° –15° 20° –15° –15° –15°
none hexane hexane hexane C6H6 toluene CH2Cl2 THF
5h
9h
7h
1h
Time
Temp
Solvent
Rh4(CO)12 (0.5 mol %), solvent
Ph
CH2Cl2, rt, 20 h O
(Ph3P)4RhH (0.3 mol%),
(EtO)3SiH (1.1 eq),
CH2Cl2, rt,1.56 h
(Ph3P)4RhH (0.2 mol%),
ClCH2Me2SiH (1.1 eq),
CH2Cl2, 50°, 24 h
(Ph3P)4RhH (0.5 mol%),
PhMe2SiH (1.1 eq),
C6H6, rt, 5 h
PMHS-Pd nanocomposite,
PMHS, Pd/C, EtOH, 80°
CCl4, 50°, 6 h
Et3SiH (3 eq), TFA (10 eq),
Conditions
(100)
(94)
Ph I
Et2MeSiO
O
OSi(OEt)3
(85), E:Z = 1:2
(73), E:Z = 33:67
(53)
(93)
(98)
(64)
(85)
(95)
(97)
(42)
I + II
+
I:II
78:22
85:15
87:13
81:19
88:12
86:14
77:23
50:50
Ph II
Et2MeSiO
(75), E:Z = 56:44
OSiMe2CH2Cl
OSiMe2Ph
I I (95)
O
OH
O
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES
464
374
374
374
219
316
434, 439
Refs.
469
C5
C4-10
R3
O
O
H H Me Me H H
Me
Me
Me
Me
Ph
Me
O
R2
R1
R1
R2
Ph
H
Me
Me
H
H
R3 30 min 15 min 30 min 15 min 30 min
60° 60° 50° 50° 60° 60°
Ph3Si Et3Si Et3Si Et3Si
none MePh2P MePh2P
n-C5H9 n-C5H9 Ph
0°
15°
0°
Temp
20 h
6h
6.5 h
Time
CH2Cl2, rt, 12 h
(Ph3P)4RhH (0.3 mol%),
PhMe2SiH (1.1 eq),
(Ph3P)4Pd (0.005 eq), CHCl3, rt, 0.5 h
Ph2SiH2 (1.2 eq), ZnCl2 (0.16 eq),
DMI (0.5 eq), 80°, 10 h
PhMe2SiH (2 eq), CoCl2 (0.175 eq),
or CD3CN, DMI (0.5 eq), rt, 5 h
Cl3SiH (2 eq), CoCl2 (0.175 eq), neat;
Ligand
R
ligand, RCHO, hexane
Et2MeSiH, Rh4(CO)12 (0.5 mol%),
PhMe2Si
Time 15 min
Temp
Et3Si
R3Si
R3SiH (1 eq), (Ph3P)3RhCl (0.5 mol%)
(90)
(96)
(98)
(94)
(97)
(95)
I
O
R1
(83)
(92)
OSiMe2Ph
I (99)
I (65)
I
O
R
Et2MeSiO
R3
OSiR3 R2
I:II 73:27 74:26 84:16
(21) (45) (100)
R
Et2MeSiO
I + II
+ II
O
374
436
451
451
464
411
470
C6 O
57:43
(95) (93) (90) (98) (99) (95)
Et3Si (i-Pr)2HSi Et2HSi PhMeHSi Ph2HSi PhH2Si
reflux, 23 h
Mo(CO)6 (3-5 mol%), THF,
PhSiH3 (1.3-1.5 eq),
reflux, 24 h
Mo(CO)6 (3-5 mol%), THF,
II (95)
II (5)
13:87
(98)
99:1
93:7
61:39
1:99
1:99
0:100
(99)
EtMe2Si
Ph2SiH2 (1.3-1.5 eq),
(75)
(90)
Product(s) and Yield(s) (%)
II (10)
PhMe2Si
+
O
I:II
I + II
I (71)
II (99)
II
I
OH
I + II
R3Si
R3SiH (1.1 eq), (Ph3P)3RhCl
HCl, CH2Cl2, rt, 4 h
Et3SiH (3 eq), AlCl3 (1.2 eq),
(Ph3P)4Pd (0.007 eq), CHCl3, rt, 1 h
Ph2SiH2 (2.0 eq), ZnCl2 (0.35 eq),
CH2Cl2, –5°, 1 h
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
CHCl3, 60°, 4 h
Et3SiH (3 eq), TFA (6 eq),
Conditions
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
450
450
435
136
436
449
434
Refs.
471
O
O
O
140°, 1.5 h
Ph2SiH2 (0.5 eq), o-C6H4(CO2K)2,
(0.4 mol%), CH2Cl2, rt, 4 h
Ph2SiH2 (1.3 eq), (Ph3P)4RhH
2. BnOCH2CHO, TiCl4, CH2Cl2, –78°
MeC6H5, rt, 1 h
1/6 [(Ph3P)CuH]6 (5 mol%),
1. HMe2SiOSiMe2H (1.5 eq),
(0.3 mol%), CH2Cl2, rt, 10 h
ClCH2Me2SiH (1.1 eq), (Ph3P)4RhH
(0.2 mol%), CH2Cl2, rt, 6 h
PhMe2SiH (1.1 eq), (Ph3P)4RhH
C6H6, 20°, 7 h
Rh4(CO)12 (0.5 mol%),
PhCHO, Et2MeSiH,
MePh2P, C6H6, 20°, 7 h
Rh4(CO)12 (0.5 mol%),
PhCHO, Et2MeSiH,
I
HO
O
Ph
O
(83)
OBn
II
+
(79)
OH
(83), E:Z = 4:1
(82), E:Z = 77:23
II III I + II + III (70), I:II:III = 65:0:35
+
+
Et2MeSiO
I + II (86), I:II = 80:20
OSiMe2CH2Cl
OH
I
I
O
OSiMe2Ph
I + II (0)
Ph
Et2MeSiO
O
319
374
455
374
374
464
464
472
C6
O +
OH
(Ph3P)4Pd (0.005 eq), rt, 0.5 h
Ph2SiH2 (1.2 eq), ZnCl2 (0.16 eq),
DMA, 0° to rt, 17 h
PPh3 (50 mol%), TBAF (20 mol%),
PhMe2SiH (1.2 eq), CuCl (50 mol%),
DMA, 0° to rt, 2 h
(Ph3P)3CuF•2 EtOH (1.0 eq),
PhMe2SiH (2 eq),
DMA, 0° to rt, 17 h
PPh3 (50 mol%), TBAF (25 mol%),
PhMe2SiH (1.2 eq), CuCl (50 mol%),
2. Add enone, 0° to rt, 2 h
DMA, 0°, 0.5 h
1. PhMe2SiH (2 eq), (Ph3P)3CuF•2 EtOH,
(Ph3P)3CuF•2 EtOH (1 eq)
PhMe2SiH (2 eq), DMA,
II (100)
II (67)a
II (92)
III (67)
III (92)
III (91)
436
444
444
444
444
446
445
III (100)
PhMe2SiH (4 eq), CuCl (2 eq), DMI, rt, 22 h
93
I + II (91), I:II = 97:3
H, 0°, 5 h
319
93
II III I + II + III (65), I:II:III = 60:10:30
+
O
Refs.
I (85)
I
OH
Product(s) and Yield(s) (%)
G, 0°, 2 h
Ph2SiH2 (0.5 eq), CsF, 140°, 1.5 h
Conditions
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
473 CH2Cl2, rt, 12 h
(Ph3P)4RhH (0.3 mol%),
PhMe2SiH (1.1 eq),
CH2Cl2, rt, 0.5 h
(Ph3P)4RhH (0.1 mol%),
ClCH2Me2SiH (1.1 eq),
–78° to –30°
BnOTMS (0.83 eq), CH2Cl2,
Et3SiH (1 eq), TMSOTf (0.1 eq),
L-D, CH2Cl2, rt, 2 h
or CD3CN, DMPU (0.25 eq), rt, 5 h
Cl3SiH (2 eq), CoCl2 (0.05 eq), neat,
CD3CN, DMI (0.5 eq), rt, 5 h
Cl3SiH (2 eq), CoCl2 (0.175 eq),
THF, reflux, 4 h
Mo(CO)6 (3-5 mol%),
PhSiH3 (1.3-1.5 eq),
PPh3 (0.02 eq)
PhSiH3 (1.01 eq), Ni,
MeC6H5, 8 min
[(Ph3P)CuH]6 (5 mol%),
PhSiH3 (1.5 eq),
D
(50)
OSiMe2Ph
OSiMe2CH2Cl
OBn
O
II (88)
II (88)
II (25)
II (93.1)
II (100)
(84)
(83)
374
374
341
101
451
451
450
438
447
474
C6
O
O
O
O
O
O
I
OH
OH
Ph
+
(Ph3P)4Pd (0.10 eq), CHCl3, rt, 1 h
Ph2SiH2 (2.0 eq), ZnCl2 (1.0 eq),
3. TsOH (cat.), C6H6, reflux, 1.5 h
BF3•OEt2, CH2Cl2
2. 2-Br-5-benzyloxybenzaldehyde,
1/6 [CuH(PPh3)]6 (5 mol%), MeC6H5, rt
1. PhMe2SiH (1.5 eq),
MePh2P, MeC6H5, 0°, 5 h
O
O
O
O
(95)
OBn
Br
O
(77)
NO2
II
(73)
OH Ph I + II (57), I:II = 75:25
Product(s) and Yield(s) (%)
Et2MeSiH, PhCHO, Rh 4(CO)12 (0.5 mol%), I + II (75), I:II = 73:27
MeC6H5, 15°, 15 h
Rh4(CO)12 (0.5 mol%),
Et2MeSiH, PhCHO,
2. 4-O2NC6H4CHO, BF3•OEt2, CH2Cl2, –78°
MeC6H5, rt, 1 h
1/6 [CuH(PPh3)]6 (5 mol%),
1. PhMe2SiH, (1.5 eq),
Conditions
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
436
455
464
464
455
Refs.
475
C6-12
O
O
(65) (42)
MeI n-BuI
BnCH2
BnCH2
Temp rt rt rt 50 rt rt rt
Solvent CH2Cl2 THF CH2Cl2:MeC6H5 (1:1) CH2Cl2 CH2Cl2:MeC6H5 (1:1) CH2Cl2:MeC6H5 (1:1) CH2Cl2:MeC6H5 (1:1)
R
Me
Me
Me
BnCH2
BnCH2
BnCH2
BnCH2
2. BnBr, TBAT (1.2 eq), solvent
MeC6H5, 0°, 2-3 h
NaOBu-t (5%), (S)-p-Tol-BINAP,
(69)
(67)
(64)
(60)
(62)
(53)
(62)
R
(64)
Allyl bromide
BnCH2
R
(67)
BnBr
BnCH2
O
(52)
1-Bromo-3-methyl-2-butene
Me
1. Ph2SiH2 (0.53 eq), CuCl (5%),
(52)
BrCH2CO2Et
Me
Bn
85:15
73:27
76:24
94:6
80:20
94:6
dr 92:8
(62)
BnBr
Me
R1
R2
R2X
CH2Cl2/MeC6H5 (1:1), rt, 24 h
O
R1
R1
2. R2X, TBAT (1.2 eq),
MeC6H5, 0°, 2-3 h
NaOBu-t (5%), (S)-p-Tol-BINAP,
1. Ph2SiH2 (0.53 eq), CuCl (5%),
459
459
476
C6-9
C6
R1
O
O
R2 H H H H Me
H
Cl
Me
MeO
Me
R3
R2
R1
O
O
(85) (96) (90) (98) (90)
H H Me
OH
OH
H
R1
I (81)
OH
OH
H
R3
CH2Cl2, reflux, 30 min
NaI (10 mol%), TMSCl (10 mol%),
HMe2SiOSiMe2H (1.5 eq),
EtOH, reflux
(Bu2(AcO)Sn)2O (2 mol%),
PMHS (10% xs),
60-65°, 1 h
Et3SiH (1.5 eq), TFA, (13 eq),
Conditions
I
R3
R2
(98)
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
314, 357
316
393
Refs.
477
C6-15
R1
R2 Me Me Ph Me Me Me Me Me Me Ph Ph
R1
Et
Et
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
O
R2 1.2 eq
(87) (82) (65)
4-MeOC6H4 Ph
(73)
(40)
(78)
(59)
Et2CH
t-Bu
Bn
Ph
4-O2NC6H4
(75)
(46)
4-MeOC6H4 4-MeOC6H4
(40)
Ph
O
(61)
R1
4-MeOC6H4
R3
R3CHO (1 eq), EtCN, –78° to rt, 1h
Et3SiH (1 eq), InBr3 (10 mol%),
R3
78:22
>99:1
90:10
>99:1
>99:1
92:8
>99:1
90:10
>99:1
>99:1
>99:1
syn:anti
OSiEt3
R2 760
478
C7
O
O
I
+
II (74)
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
II (100)
II (100)
CH2Cl2, –5°, 1 h
OH
+
II (97), II:I = 100:0
I
I
OH
I (73)
I (73)
O
PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)
[(Ph3P)CuH]6 (5 mol%), MeC6H5, 18 h
PhSiH3 (1.5 eq),
(Ph3P)3RhCl (10 mol%), 0°, 340 min
Ph2SiH2 (1.1 eq),
(Ph3P)3RhCl (10 mol%), 50°, 30 h
Et3SiH (1.1 eq),
CH2Cl2, rt, 4 h
(Ph3P)4RhH (0.3 mol%),
Ph2SiH2 (1.3 eq),
CH2Cl2, –5°, 1 h
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
CH2Cl2, –5°, 1 h
TMSH (1.2 eq), TiCl4 (2.4 eq),
(Ph3P)3RhCl (10 mol%), 45°, 4 h
Et3SiH (1.1 eq),
Conditions
II
II
OH
II (97), I:II = 0:100
I (90), I:II = 98:2
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
449
438
447
435
435
374
449
449
435
Refs.
479
C8
O
O
O
Cl
Pr-i
CO2H
CF3 OH
MeC6H5, 8 min
[(Ph3P)CuH]6 (5 mol%),
PhSiH3 (1.5 eq),
PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)
NaOBu-t (0.1 mol%), MeC6H5, rt, 1 h
PMHS (1.6 eq), 209 (0.1 mol%),
Et3SiH (3 eq), TFA, rt, 48 h
2. n-C5H11CHO, TiCl4, CH2Cl2, –78°
MeC6H5, rt, 39 h
1/6 [(Ph3P)CuH]6 (5 mol%),
1. HMe2SiOSiMe2H (1.5 eq),
(0.5 mol%), CH2Cl2, 50°, 24 h
PhMe2SiH (1.1 eq), (Ph3P)4RhH
MeC6H5, rt, 24 h
1/6 [(Ph3P)CuH]6 (5 mol%),
HMe2SiOSiMe2H (1.5 eq),
I
O
O
Cl
I (85)
O
O
(98)
(81)
CO2H
CF3 OH
Pr-i
(89)
C5H11-n
OH
OSiMe2Ph
(72)
(82)
(85)
OSi(Me)2OSiMe2H
447
438
454
453
455
374
455
480
C8
O
O
MeC6H5, 46 h
[(Ph3P)CuH]6 (5 mol %),
PhSiH3 (1.5 eq),
CD3CN, DMI (0.5 eq), rt, 12 h
Cl3SiH (2 eq), CoCl2 (0.175 eq),
DMI, rt, 22 h
PhMe2SiH (4 eq), CuCl (2 eq),
–78°, 1 h
2. Aldehyde, BF3•OEt2, CH2Cl2,
MeC6H5, rt, 4 h
[(Ph3P)CuH]6 (18 mol%),
1. PhMe2SiH, (1.5 eq),
CHO
MeC6H5, rt, 4 h Ts N 2. , TiCl4, CH2Cl2, –78°
1/6 [(Ph3P)CuH]6 (5 mol%),
1. PhMe2SiH (1.5 eq),
CH2Cl2, rt, 4 h
(Ph3P)4RhH (0.3 mol%),
ClCH2Me2SiH (1.1 eq),
CH2Cl2, rt, 12 h
(Ph3P)4RhH (0.4 mol%),
PhMe2SiH (1.1 eq),
Conditions
O
I
R
OH
OH (82)
(100) cis:trans = 97:3
(68)
cyclohex-3-enyl (80)
R
4-O2NC6H4CHO 4-O2NC6H4
carbaldehyde
cyclohex-3-ene-
Aldehyde
N Ts
I (100), single isomer
I (50)
O
O
Product(s) and Yield(s) (%)
(96)
(80)
OSiMe2CH2Cl
OSiMe2Ph
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
447
451
445
455
455
374
374
Refs.
481
O
MePh2P, C6H6, 20°, 15 h,
Rh4(CO)12 (0.5 mol%),
PhCHO, Et2MeSiH,
(Ph3P)3RhCl (10 mol%), C6H6, rt, 1 h
Ph2SiH2 (1.1 eq),
C6H6, rt, 6 h
PMHS-Pd nanocomposite,
CHCl3, rt, 4 h
(Ph3P)4Pd (0.013 eq),
Ph2SiH2 (1.8 eq), ZnCl2 (0.38 eq),
(Ph3P)4Pd (0.013 eq), rt, 4 h
Ph2SiH2 (1.8 eq), ZnCl2 (0.38 eq),
THF, reflux, 4.5 h
Mo(CO)6 (3-5 mol%),
PhSiH3 (1.3-1.5 eq),
CD3CN, DMI (0.5 eq), rt, 2 h
Cl3SiH (2 eq), CoCl2 (0.175 eq),
C6H6, 50°, 5 h
(Ph3P)3RhCl (10 mol%),
Et3SiH (1.1 eq),
CH2Cl2, 50°, 24 h
(Ph3P)4RhH (0.5 mol%),
PhMe2SiH (1.1 eq),
O
III
(75)
+
O
Ph
OH
(69)
II
OH
(87) cis:trans = 92:8
I + II (96), I:II = 97:3
III (97)
III (85)
III (—)
III (100)
I
OSiEt3
OSiMe2Ph
I (95), I:II = 87:13
464
435
219
436
436
450
451
435
374
482
C9
C8-17
R
CH2Cl2, –78°
2. Me2CHCH2CHO, BF3•OEt2,
MeC6H5, rt, 3 h
1/6 [(Ph3P)CuH]6 (5 mol%),
1. PhMe2SiH (2.5 eq),
MeC6H5, 6 h
[(Ph3P)CuH]6 (0.5mol%),
PhSiH3 (1.5 eq),
DMI, rt, 20 h
PhMe2SiH (4 eq), CuCl (2 eq),
CH2Cl2, –5°, 1 h
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
Pr-i
Pr-i O
O
I
OH
(73)
I (13)
(75)
2-C4H3S
CH2Cl2, –5°, 1 h
(68)
2-C4H3O O
(72)
2-C10H7
O
(87)
OH
4-CF3C6H5
I (53)
R
O
(38)
TMSH (1.2 eq), TiCl4 (2.4 eq),
Co(dpm)2 (5 mol%), rt
PhSiH3 (1.2 eq),
Ph
CHO
Me
R
Pr-i
O
O
Conditions
(99)
(66)
(89)
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
455
447
445
449
449
461
Refs.
483
n-C5H11
O
CH2Cl2, –78°
CHO, BF3•OEt2,
DMA, 0° to rt, 2 h
PPh3 (25 mol%), TBAF (20 mol%),
PhMe2SiH, CuCl (25 mol%),
2. Add enone, 0° to rt, 2.5 h
DMA, 0°, 0.5 h
(Ph3P)3CuF•2 EtOH,
1. PhMe2SiD (2 eq),
DMA, 0° to rt, 2 h
PPh3 (25 mol%), TBAF (20 mol%),
PhMe2SiH (1.2 eq), CuCl (25 mol%),
2. Add enone, 0° to rt, 2.5 h
0°, 0.5 h
(Ph3P)3CuF• 2 EtOH, DMA,
1. PhMe2SiH (2 eq),
(Ph3P)3CuF•2 EtOH (1 eq)
PhMe2SiH (2 eq), DMA,
2.
Bu3Sn
MeC6H5, rt, 2 h
1/6 [(Ph3P)CuH]6 (5 mol%),
1. PhMe2SiH (1.5 eq),
CH2Cl2, –78°
2. ClCH2CH2OCH2CHO, BF3•OEt2,
MeC6H5, rt, 2 h
1/6 [(Ph3P)CuH]6 (5 mol%),
1. PhMe2SiH (1.5 eq),
II (77)
n-C5H11
I (77)
I (91)
n-C5H11
Pr-i
O
Pr-i
O
D
OH
OH
II
I
O
O
O
(76)
(87)
(62) >99% D
(91)
SnBu3
Cl
444
444
444
444
446
455
455
484
C10
C9
O
O
n-C5H11
O
O
rt, 20 min
Ph2SiH2 (1.1 eq), (Ph3P)3RhCl (10 mol%),
C6H6, rt, 2 h
(Ph3P)3RhCl (10 mol%),
EtMe2SiH (1.1 eq),
Et2SiH2, (Ph3P)3RhCl
i-PrOH, DCE
PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),
PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)
3. Allyl bromide
2. Add enone, 0°, 45 min
DMA, 0°, 0.5 h
1. PhMe2SiH (2 eq), (Ph3P)3CuF•2 EtOH,
3. D2O
2. Add enone, 0°, 45 min
DMA, 0°, 0.5 h
1. PhMe2SiH (2 eq), (Ph3P)3CuF•2 EtOH,
Conditions
O
I
I
EtMe2SiO
OH
O
n-C5H11
n-C5H11 D O
O
+
+
(—)
O
(81.9)
(45)
II
II OH
OH
(67) 85% D
(74)
I (98), I:II = 0:100
I (97), I:II = 78:22
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
435
435
435
448
438
444
444
Refs.
485
O
50:50 50:50 0:100 0:100 I + II (—)
Et3Si (n-Pr)3Si Et2HSi Ph2HSi R3SiH (1.1 eq),
0:100 0:100
Ph2HSi
Mo(CO)6 (3-5 mol%), THF, reflux, 3 h
PhSiH3 (1.3-1.5 eq),
Mo(CO)6 (3-5 mol%), THF, reflux, 15 h
Ph2SiH2 (1.3-1.5 eq),
I + II (100)
+
II
O
(90) cis:trans = 1:1
I + II (90), I:II = 4.5:1
I
II (—) O
75:25
Et2HSi
Et2SiH2, (Ph3P)3RhCl
50:50
(n-Pr)3Si
50:50
PhMe2Si
Et3Si
R3Si
I:II
75:25
PhMe2Si
(Ph3P)3RhCl (0.5 mol%), 50°, 2 h
I:II
I + II (—)
O
R3Si
R3SiH, (Ph3P)3RhCl
(Ph3P)4Pd (0.018 eq), CHCl3, rt, 3 h
Ph2SiH2 (1.55 eq), ZnCl2 (0.4 eq),
I:II = 4.5:1 450
450
435
437
452
436
486
C10
O
O
O
O
CH2Cl2, rt, 12 h
(Ph3P)4RhH (0.4 mol%),
Ph2SiH2 (1.3 eq),
THF, reflux, 11.5 h
Mo(CO)6 (3-5 mol%),
PhSiH3 (1.3-1.5 eq),
i-PrOH
PhSiH3 (2 eq), Mn(dpm)3 (3 mol%),
(Ph3P)4Pd (0.013 eq), CHCl3, rt, 2 h
Ph2SiH2 (1.7 eq), ZnCl2 (0.52 eq),
DMI, rt, 22 h
PhMe2SiH (4 eq), CuCl (2 eq),
DMA, 0° to rt, 4.5 h
PPh3 (160 mol%), TBAF (150 mol%),
PhMe2SiH, CuCl (160 mol%),
2. Add enone, 0° to rt, 24 h
(Ph3P)3CuF•2 EtOH, DMA, 0°, 0.5 h
1. PhMe2SiH (2 eq),
(Ph3P)3CuF•2 EtOH (1 eq)
PhMe2SiH (4 eq), DMA,
Conditions
O
I
I (0)
I (50)
O
(83)
(84) cis:trans = 65:35
(85)
(85) dr = 8:1
Product(s) and Yield(s) (%)
I (89) cis:trans = 1:4
I (87)
I
O
O
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
374
450
448
436
445
444
444
446
Refs.
487
Ph
O
(69) (95) (49) (—)
(—) (36) (—)
1 0.05 1 1 1
1 2 2 2 2
PhMe2Si PhMe2Si Et3Si Ph2HSi PhCl2Si
(58) (49) (0)
(34) (36) (0)
1.5 h 3.5 h 18 h —
Et3Si (EtO)3Si Ph2HSi PhCl2Si
0° to rt, 6 h
Ph2SiH2 (1.1 eq), (Ph3P)3RhCl,
45°, 15 h I:II = 60:40
I:II = 37:63
(96)
(—)
2h
PhMe2Si
Et3SiH (1.1 eq), (Ph3P)3RhCl,
II (>99)
I (—)
Time
R3Si
DMA, 0° to rt, 0.5 h
(Ph3P)3CuF•2 EtOH (1.0 eq), I + II
(63)
(—) (trace)
1
2
R3SiH (2 eq),
II (>99)
I (—)
y
x
II
R3Si
Ph
I
OH
PhMe2Si
+
I
R3SiH (x eq), DMA, (Ph3P)3CuF•2 EtOH (y eq)
I (100)
Ph Ph2SiH2 (0.5 eq), CsF, rt, 30 min
(EtO)3SiH, CsF, rt, 30 min
O
(100)
435
435
444
446
319
83
488
C10
Ph
O
12 h 21 h 12 h
(CuOTf)2•C6H6 Cu2O CuCN
Temp
0° to rt
60°
0° to rt
0° to rt
0° to rt
0° to rt
Mo(CO)6 (3-5 mol%), THF, reflux, 7 h
Ph2SiH2 (1.3-1.5 eq),
rt, 30 min
Ph2SiH2 (2.3 eq), CsF (1 eq),
(Ph3P)4Pd (0.0009 eq), CHCl3, rt, 2 h
Ph2SiH2 (1.3 eq), ZnCl2 (0.3 eq),
2. TBAF, MeOH, rt, 30 min
MeC6H5, rt, 3 h
1/6 [(Ph3P)CuH)]6 (5 mol%),
1. HMe2SiOSiMe2H,
CH2Cl2, 0°, 1 h
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
solvent, 0° to rt
(Ph3P)3CuF•2 EtOH (1.0 eq),
PhMe2SiH (2 eq),
4h 21 h
CuF(PPh3)3 CuCl
2h
Time CuF(PPh3)3•2 EtOH
PhMe2SiH (3 eq), DMA
Conditions
II (95)
II (100)
II (100)
II (82)
II (36)
II
II
(64)
(48)
(27)
(55)
(>99)
II
(42)
12.5
MeC6H5
(80)
(57)
6h 2.5 h
(40)
(92)
THF
2.5 h
2h
Time
NMP
DMF
DMA
Solvent
(trace) (trace)
(—)
(trace)
(—)
(—)
(—)
I
I + II
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
450
83
436
455
449
444
444
Refs.
489 O Ph
O
(Ph3P)3RhCl (10 mol%), 0°, 30 min
Et2SiH2 (1.1 eq),
(Ph3P)3RhCl (10 mol%), 80°, 25 h
Et3SiH (1.1 eq),
0° to rt, 6 h
Ph2SiH2 (1.1 eq), (Ph3P)3RhCl,
45°, 15 h
Et3SiH (1.1 eq), (Ph3P)3RhCl,
MePh2P, C6H6, 20°, 3.5 h
Rh4(CO)12 (0.5 mol%),
PhCHO, Et2MeSiH,
2. BnOCH2CHO, TiCl4, CH2Cl2, –78°
MeC6H5, rt
1/6 [(PPh3)CuH]6 (2 mol%),
1. PMHS (1.25 eq),
2. 4-O2NC6H4CH2Br, CH2Cl2, rt, 3 h
MeC6H5, rt, 2 h
OH
I
I
O
I
O
OBn
+
NO2
Ph
Ph
O + II
II
Et2MeSiO
(83)
(57)
I + II (88), I:II = 80:20
Bn
O
O
I (98), I:II = 3:97
I (—)
Ph
Et2MeSiO
Ph
Ph
1. HMe2SiOSiMe2H (0.55 eq), 1/6 [(Ph3P)CuH]6 (2 mol%),
II (96.9)
II (100)
PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)
Mo(CO)6 (3-5 mol%), THF, reflux, 1.5 h
PhSiH3 (1.3-1.5 eq),
OH
Bn
O
I (96), I:II = 94:6
435
435
435
435
464
455
455
438
450
490
C11
O
TBSO
O
O
Ph O
O
O
O
CH2Cl2, 1 h
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
MeC6H5, 10 min
PhSiH3 (1.5 eq), [(Ph3P)CuH]6 (5 mol%),
MeC6H5, rt, 1 h
NaOBu-t (0.1 mol%),
PMHS (1.6 eq), 209 (0.1 mol%),
NaOBu-t (0.1 mol%), MeC6H5, rt, 1 h
PMHS (1.6 eq), 209,
CH2Cl2, reflux, 30 min
NaI (10 mol%), TMSCl (10 mol%),
HMe2SiOSiMe2H (1.5 eq),
Et3SiH (5 eq), TFA (26 eq), 60-65°, 10 h
Et3SiH (4 eq), TFA (20 eq), 60-65°, 8 h
50°, 60 min
Et3SiH (1 eq), (Ph3P)3RhCl (0.5 mol%),
Conditions
O
TBSO
O
O
I (75)
Ph O
OH
OH
I
(70)
(95)
(92)
–78°
0°
Temp (50)
(53) cis:trans = 9:1
(85) dr = 4:1
(60)
(50)
OSiEt3
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
449
447
454
454
314
393
393
411
Refs.
491
C12
O
Ph
O
O
O
Ph
O
O
CHO
Cl
O
CO2Et
CO2Me
O
O
NaOBu-t (3 mol%), MeC6H5, rt, 3 h
PMHS (1.6 eq), 209 (0.1 mol%),
PhSiH3 (1.2 eq), Co(dpm)2 (5 mol%), rt
BF3•OEt2 (2 mol%), TFA, rt, 0.5 h
Et3SiH or EtMe2SiH (4 eq),
Et3SiH (xs), BF3•OEt2, 80-95°
Et3SiH (6 eq), BF3 (xs), 20°, 6 h
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),
CH2Cl2, –78°
Et3SiH (2 eq), SnCl4 (0.1 eq),
CH2Cl2, –78°
Et3SiH (2 eq), BF3•OEt2 (1.1 eq),
DMI, rt, 21 h
PhMe2SiH (4 eq), CuCl (2 eq),
H
O
Ph
O
Ph
O
(71)
OH (70)
(94) dr = 5:1
Cl
OH (96)
(91)
+
O
(81) cis:trans = 98:2
(64)
CO2Me
OSiEt3
H
CO2Et
H H I
O
I (66-74)
I
I (61)
O
O
(14)
454
461
396
442
442
471
463
463
445
492
C13
C12
O
O
Bn
O
O
O
O
CH2Cl2, 0°, 1 h
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
(95)
Et3Si
78:22
98:2 85:15 (95)
+
(94)
O
(60)
(87)
EtMe2Si
I
O
PhMe2Si
Bn
OH
(99)
I:II
I (78)
O
I (59)
I
O
II
Product(s) and Yield(s) (%)
I + II
R3Si
R3SiH (1.1 eq), (Ph3P)3RhCl
2. Allyl bromide, TBAT (1.2 eq)
MeC6H5, 0°, 2-3 h
NaOBu-t (5%), (S)-p-Tol-BINAP,
1. PMHS (0.53 eq), CuCl (10%),
2. P(OEt)3 (1.1 eq)
i-PrOH, DCE, O2
1. PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),
2. P(OEt)3 (1.1 eq)
i-PrOH, DCE, O2
1. PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),
i-PrOH, DCE
PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),
Conditions
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
OH
449
435
459
465
465
448
Refs.
493
78:22 86:14
3h 12 h
none C6H6 (0.2 M)
0:100
Et2HSi Ph2HSi
2. P(OEt)3 (1.1 eq)
Mn(dpm)3 (3 mol%), i-PrOH, DCE, O2
1. PhSiH3 (1.3 eq),
i-PrOH, DCE
PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),
(Ph3P)3RhCl (10 mol%), 50°, 2 h
Et3SiH (1.1 eq),
(Ph3P)3RhCl (10 mol%), C6H6, rt, 15 h
EtMe2SiH (1.1 eq),
[(Ph3P)CuH]6 (5 mol%), MeC6H5, 47 h
PhSiH3 (1.5 eq),
(Ph3P)3RhCl (10 mol%), rt, 30 min
Ph2SiH2 (1.1 eq),
(Ph3P)4Pd (0.019 eq), CHCl3, rt, 2 h
I (25)
OH
O
I (96), I:II = 100:0
I (94), I:II = 98:2
I (96)
I (98), I:II = 100:0
I (96)
0:100
Et3Si
Ph2SiH2 (2.5 eq), ZnCl2 (0.35 eq),
91:9 44:56
PhMe2Si
I:II
R3Si
I + II (—)
64:36
3h
none
R3SiH, (Ph3P)3RhCl
I:III
Time
I (—) +
Solvent
(10-20 mol%), solvent, 50°
Et3SiH (1.2 eq), (Ph3P)3RhCl,
(51)
III
OSiEt3 (—)
465
448
435
435
447
435
436
437, 452
435
494
C13
Ph
Ph
Ph
i-Pr
O
O
O
O
O
Pr-i
O
H
i-Pr
DCE, rt, 30 min
Co(dpm)2 (5 mol%),
PhSiD3 (120 mol%),
DCE, rt, 30 min
Co(dpm)2 (5 mol%),
PhSiH3 (120 mol%),
CH2Cl2, –78°
Et3SiH (2 eq), SnCl4 (0.1 eq),
CH2Cl2, –78°
Et3SiH (10 eq), BF3•OEt2 (1.1 eq),
CH2Cl2, –78°
Et3SiH (10 eq), BF3•OEt2 (1.1 eq), I
(18)
Pr-i
Ph
Ph
D
O
O
OH
OH
I (53) + II (9) +
I (19) + II (62)
Ph
O
(—)
(—)
Ph
+
+
O
Ph
Ph
II
O
5.7:1 epimer ratio
+
(24)
(96)
CH2Cl2, –78°
OSiEt3
O
D
O
i-Pr
Pr-i
OH
(12)
(59)
O
Product(s) and Yield(s) (%)
Et3SiH (10 eq), BF3•OEt2 (1.1 eq),
Et3SiH, (Ph3P)3RhCl
Conditions
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
463
(—)
460
460
463
463
463
2.6:1 epimer ratio
(69)
452
Refs.
495
C13-15
Ph
Cl
O
Ph
0.1 0.1 0.1 0.005
Ph2SiH2 MeC6H5 THF
PMHS Ph2SiH2 THF PMHS
6h
1h
1h
1h
1h
Time
12 h 10 h 18 h
OBu-t OTHP
TBAF (5-10 mol%), HMPA, 0°
PhMe2SiH (1.1-1.2 eq),
[(Ph3P)CuH]6 (5 mol%), MeC6H5, 6 h
PhSiH3 (1.5 eq),
i-PrOH, DCE
PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),
OAc
R
O
0.1
MeC6H5
PMHS
MeC6H5
x
Solvent
R3SiH
NaOBu-t (0.1 mol%), solvent, rt
R3SiH (1.3 eq), 209 (x mol%),
Ph2MeSiH, TBAF
Time
O
Ph
OAc
PhMe2SiH, TBAF
R
O
Bn
O
I
OAc
Ph
Cl
(86)
(88)
(86)
(87)
(88)
O
I
O
OH
Ph
Bn
(77)
(86)
(95)
I + II
R
I (—) 87% selectivity
Ph
OH
I:II
87:13
91:9
84:16
+
O
(50)
Ph
(97)
II
OH
(95) 84% selectivity
R
320
447
448
454
440
440
496
C14
O
Ph
O
Bn
CO2Me
Cl
CHO
NaOBu-t (6 mol%), MeC6H5, rt, 1 h
CuCl2•2H2O (1 mol%),
PMHS (3 eq), 209,
NaOBu-t (0.1 mol%), MeC6H5, rt, 1 h
PMHS (1.6 eq), 209 (0.1 mol%),
Co(dpm)2 (5 mol%), DCE, 35°
PhSiH3 (1.2 eq),
BF3•OEt2 (2 mol%), TFA, rt, 0.5 h
Et3SiH or EtMe2SiH (4 eq),
Ph
Bn
OH
I (87) dr = 4:1
I
O
O
CO2Me
Cl
(35)
(96)
(97)
(98)
Product(s) and Yield(s) (%)
(90) dr = 5:1
OH
CO2Me
O
O
NH2
CO2Me
BF3•OEt2 (2 mol%), TFA, rt, 12 h
O
NH2
Et3SiH or EtMe2SiH (4 eq),
CO2Me
O
O
O
CO2Me
BF3•OEt2 (2 mol%), TFA, rt, 12 h
Et3SiH or EtMe2SiH (4 eq),
NH2
O
O
NH2 O
Conditions
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
454
454
461
396
396
396
Refs.
497
C15
O
O
MeHN
CO2Me
R
O
BF3•OEt2 (2 mol%), TFA, rt, 24 h
Et3SiH or EtMe2SiH (4 eq), CO2Me
R
O
O
O
BF3•OEt2 (2 mol%), TFA, rt, 24 h
Et3SiH or EtMe2SiH (4 eq),
O
CO2Me
O
O
60-65°, 0.5 h
CO2Me
MeHN
O
O Et3SiH (10 eq), TFA (20 eq),
OH
OH
O
60-65°, 20 h
Et3SiH (5 eq), TFA (20 eq),
Bn
OSiEt3
O
O
NaOBu-t (0.1 mol%), MeC6H5, rt, 1 h
PMHS (1.6 eq), 209 (0.1 mol%),
O
Bn
TIPSO
O
Et3SiH, Pt[(vinylMe2Si)2O]2
TIPSO
O
OH
OH
(93)
(96)
Time OMe
8h
NHMe 24 h
R
(98)
(99)
(54)
(98)
(98)
396
396
393
393
454
456
498
C15
Ph
O Ph
Ph2SiH2 (2.3 eq), CsF (1 eq), 0°, 1 h
DMA, 0° to rt, 2 h
PPh3 (110 mol%), TBAF (100 mol%),
PhMe2SiH (1.2 eq), CuCl (110 mol%),
DMA, 0° to rt, 1 h
PPh3 (20 mol%), TBAF (10 mol%),
PhMe2SiH (1.2 eq), CuCl (20 mol%),
(1.0 eq), DMA, 0° to rt, 3 h
PhMe2SiH (2 eq), (Ph3P)3CuF•2 EtOH
(Ph3P)3CuF•2 EtOH (1 eq)
PhMe2SiH (2 eq), DMA,
0° to rt, 6 h
PhSiH3 (1.1 eq), (Ph3P)3RhCl,
0° to rt, 6 h
Ph2SiH2 (1.1 eq), (Ph3P)3RhCl,
C6H6, rt, 15 h
Et3SiH (1.1 eq), (Ph3P)3RhCl,
CHCl3, 60°, 7 h
Et3SiH (3 eq), TFA (6 eq),
Ph2SiH2 (0.5 eq), CsF, rt, 30 min
Conditions
I
(80)
+ Ph
Ph
+ Ph
I + II (95), I:II = 95:5
Ph
I (95) + II (5)
II (94)
II (25)
II (98)
II (98)
II (—)
II (—)
II (—)
Ph
Ph
OH
(17)
Ph
II
O Ph
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
Ph
83
444
444
444
446
435
435
435
434
319
Refs.
499
C16
C15-23
C15-16
Ph
Ph
Ph
O
OMe
O
n
O
OMe
Ar
Ar
O
O
O
H
Ar = 4-BrC6H4
60-65°, 20 h
Et3SiH (4 eq), TFA (10 eq),
CCl4, 50°, 6 h
Et3SiH (1 eq), TFA (10 eq),
rt, 30 min
Co(dpm)2 (5 mol%), DCE,
PhSiH3 (120 mol%),
(Ph3P)4Pd (0.014 eq), CHCl3, rt, 3 h
Ph2SiH2 (2.4 eq), ZnCl2 (0.77 eq),
CH2Cl2, –78°
2. Me2CHCH2CHO, BF3•OEt2,
MeC6H5, rt, 0.5 h
1/6 [(Ph3P)CuH]6 (5 mol%),
1. PhSiH3 (1.5 eq),
PMHS-Pd nanocomposite, C6H6, rt, 6 h
MeC6H5, 108 min
[(Ph3P)CuH]6 (5 mol%),
PhSiH3 (1.5 eq),
Ph
Ph
Ph O
i-Bu
Ph
O
II (95)
II (96)
OH
OH
O
n
OMe
OMe
Ar
Ar OH
O
OH
Ph
(75) (75) (75) (76) (79) (79) (77)
4-MeC6H4 4-EtC6H4 4-t-BuC6H4 4-n-C6H13C6H4 4-PhC6H4 4-BnCH2C6H4
(50)
(80) 4-FC6H4
(36)
(87)
Ph
Ar
2
1
n
(98)
(73)
393
439
460
436
455
219
447
500
C16-18
C16-17
C16
t-Bu
Ph
O
O
O
O
N
O
Ar
O
Time 7h 8h 7h 20 h 9h 9h
Ph 4-MeC6H4 4-EtC6H4 2-MeC6H4 4-MeOC6H4 4-ClC6H4
Et3SiH (5 eq), TFA (10 eq), CCl4, 50-55°
TFA, rt, 24 h
Et3SiH, BF3•OEt2,
CH2Cl2, –78°
Et3SiH (10 eq), BF3•OEt2 (1.1 eq),
Co(dpm)2 (5 mol%), 70°
PhSiH3 (2.4 eq),
Ar
n
O
Conditions
t-Bu
Ph
(78)
(67)
(68)
(53)
(74)
O
N
O
H
O
O
(54)
H
O
O
Ar
H
n
(47)
(81)
+
1
0
n (62)
(93)
O
O
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
Ph (15)
266
441
463
461
Refs.
501
C17
C16-23
C16-19
O
Ph
R1
R2
R2
O
O
O Ph
O O
4-MeOC6H4
4-MeOC6H4
Ph
Me
4-MeOC6H4
R1
Ph
R2
n
R1
R2
O
O
R1
N
O
Co(dpm)2 (5 mol%), 50°
PhSiH3 (2.4 eq),
DMA, 0° to rt, 1.5 h
PPh3 (25 mol%), TBAF (20 mol%),
PhMe2SiH, CuCl (25 mol%),
2. Enone, 0° to rt, 2 h
(Ph3P)3CuF•2 EtOH, DMA, 0°, 0.5 h
1. PhMe2SiH (2 eq),
CCl4, 50°, 6 h
Et3SiH (6 eq), TFA (10 eq),
DCE, rt, 30 min
Co(dpm)2 (5 mol%),
PhSiH3 (120 mol%),
TFA, rt, 24 h
Et3SiH, BF3•OEt2,
O
I (64)
Ph
Ph
R1 or R2
R2
R2
O
O
I
O
OH
O
(46)
Ph
Ph
O
(40)
(0)
(65)
I
(5) (50)
R1
R1
+
(52)
(85)
R1 or R2
II
O
n
I
N
O
(52)
O
H
O
H
R2
II
(90)
OMe 1
Me
R1
(92)
(92)
1
1
H
(94)
0
n
Me
H
H
H H
R2
R1
461
444
444
393
460
441
502
C18
C17
O
O
Et3SiH or EtMe2SiH (4 eq),
CO2Me
NEt2
CO2Me O O
N
Et3SiH, TFA, CH2Cl2, 42 h
BF3•OEt2 (2 mol%), TFA, rt, 12 h
Et3SiH or EtMe2SiH (4 eq),
BF3•OEt2 (2 mol%), TFA, rt, 12 h
O
H
H
CO2Me
NEt2
CO2Me O
N
O
O
O
OH
O
+
H
OH
O
O
R
O
(65)
O
(60) +
(98)
(99)
H
H
NEt2
O
BF3•OEt2 (2 mol%), TFA, rt
R
H
O
1-pyrrolidinyl
O
24 h
8h
Time
O
Product(s) and Yield(s) (%)
Et3SiH or EtMe2SiH (4 eq),
DCE, rt, 30 min
Co(dpm)2 (5 mol%),
PhSiH3 (240 mol%),
CO2Me
O
O
O
CO2Me
R
O
O
Conditions
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
O
OH
(94)
(98)
(40)
(2)
242
396
396
396
460
Refs.
503
C19
O
Ph
Me N
Ph
O
O
O
O
Ph
O
O
O
O
OH
Me N
CH2Cl2, –78°
Et3SiH (2 eq), BF3•OEt2 (1.1 eq),
CH2Cl2, –78°
Et3SiH (10 eq), Et2AlCl (1.1 eq),
DCE, rt, 30 min
Co(dpm)2 (10 mol%),
PhMeSiH2 (400 mol%),
Co(dpm)2 (5 mol%), 50°
PhSiH3 (2.4 eq),
Et3SiH, TFA, CH2Cl2, 60 h
Et3SiH, TFA, CH2Cl2, 44 h
Ph I (49)
O
+
O
II (88) + III (10)
Ph
O
H
H
OSiEt3
O
Me N
Ph
O
O
Ph
O
O
(83) +
O
(86) +
O
(75)
Ph II (36)
O
Me N
Ph (27) +
O
OH
+ Ph
H
H
O
Ph III (8)
O
O
463
463
460
461
242
(14) 242
(17)
(27)
O
OH
504
C20-21
C20
C19
Ph
Ph
Ph
H
O
O
O
O
O
O
O
Y
O
O
OTr
OTBS
SPh
O
O
Ph
Ph
Ph
DDCE, 50°
R3SiH (x eq), Co(dpm)2 (y eq),
Co(dpm)2 (5 mol%), 50°
PhSiH3 (2.4 eq),
Co(dpm)2 (5 mol%), 50°
PhSiH3 (2.4 eq),
Mn(dpm)3 (3 mol%), i-PrOH, DCE
PhSiH3 (1.3 eq),
CH2Cl2, rt, 12 h
(Ph3P)4RhH (0.5 mol%),
Ph2SiH2 (1.3 eq),
Conditions
Ph
Ph
Ph
H
O
O
O
O
O
H
OH
SPh
I
O
H
O
O
O
Ph
Ph
Ph
OTr
OTBS
Y
O
+ Ph
(63)
(62)
(100)
(56)
O
II
Y
O Ph
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
462
461
461
448
374
Refs.
505
C21
Ph
Ph
O
O
O
O
Ph
O
H
Ph
PhMeHSi
CH2
H
4.0
PhH2Si
CH2 0.10
DCE rt, 30 min
Co(dpm)2 (5 mol%),
PhSiH3 (120 mol%),
DCE, rt, 30 min
Co(dpm)2 (10 mol%),
PhMeSiH2 (400 mol%),
DCE, rt, 30 min
Co(dpm)2 (5 mol%),
PhSiH3 (240 mol%),
2. P(OEt)3 (1.1 eq)
Mn(dpm)3 (3 mol%), i-PrOH, DCE, O2
1. PhSiH3 (1.3 eq),
Mn(dpm)3 (3 mol%), i-PrOH, DCE
PhSiH3 (1.3 eq),
2.4
PhH2Si
CH2
H
0.05
1.2
PhMeHSi
O
O
0.10
4.0
PhH2Si
O
0.05
0.05
2.4
PhH2Si
O
y 0.05
x 1.2
R3Si
Y
I
O
II (—)
I (11)
Ph
O
O
+
Ph
O
H
H
H
II
(9)
H
O
O
H
(70)
O OH
O
(72) (11)
(—) (73)
(38) (41)
(69)
(—) (63)
H
Ph
H
H
I (16) (31)
II
Ph (72)
(85)
(99)
460
460
460
465
448
506
C23
AcO
AcO
O
AcO
H
H
O
O
O
O
O
CH2Cl2, rt, 1 h
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
CH2Cl2, rt, 1 h
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
Et3SiH, TFA, 30 h
Et3SiH, TFA, CH2Cl2, 48 h
CH2Cl2, rt, 0.5 h
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
Conditions
H
H
AcO
AcO
H
I (96) + II (4)
O
AcO
I
I
O
O
O
O
O
(86)
O
H
(76)
(70-80)
+
(80)
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
II
O (14)
O
449
449
242
242
449
Refs.
507
C27
C26
O
H
OMe
OMe
t-BuPh2SiO
MeO
MeO
H
O
O
CF3
OEt
OEt
O
N
(50) (45) (75) (40) (75) (50)
0.5 h 0.5 h 0.6 h 0.4 h 0.5 h —
60° 60° 60° rt rt
MeCl2Si Me2ClSi Et2(EtO)Si Me(EtO)2Si HMe2SiOSiMe2
CH2Cl2, rt, 12 h
(Ph3P)4RhH (0.4 mol%),
Ph2SiH2 (1.3 eq),
Et3SiH, (Ph3P)3RhCl
CH2Cl2, rt, 48 h
Et3SiH (3.95 eq), BF3•OEt2 (19.8 eq),
OMe
OMe
H
t-BuPh2SiO
MeO
MeO
(70)
7h
160°
(n-Pr)3Si
[—(H)(Me)SiO—]4 60°
(80)
5h
150°
Et3Si
I
Temp Time
R3Si
R3SiH, H2PtCl6, MeC6H5
H
OSiEt3
CHO
O
N CF3
(32)
(64)
(76)
374
761
443
458
508
C29
C27
a
H
O
O
C8H17-n
3
NAc Co(dpm)2 (5 mol%), 50°
PhSiH3 (2.4 eq),
CH2Cl2, rt, 10 min
Et3SiH (1.2 eq), TiCl4 (2.4 eq),
(Ph3P)4Pd (0.067 eq), CHCl3, rt, 1 h
Ph2SiH2 (1.6 eq), ZnCl2 (0.90 eq),
(Ph3P)4Pd (7.2 mol%), CHCl3, rt, 1 h
Ph2SiD2 (4 eq), ZnCl2 (4 eq),
(Ph3P)4Pd (0.03 eq), CHCl3, rt, 1 h
Ph2SiH2 (1.6 eq), ZnCl2 (0.5 eq),
The yield was determined by NMR analysis.
AcN
O
O
O
3
Conditions
AcN
O
O
O
O D
H
H
H
O
O
(92)
(71)
(100)
NAc (68)
(81) 5α:5β = 3:1
C8H17-n
3
3
Product(s) and Yield(s) (%)
TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone
461
449
436
436
436, 457
Refs.
509
C4
O OMe
Unsaturated Ester
CH2Cl2, 45°, 3 h
[Rh(cod){P(OPh)3}2]OTf (1 mol%),
Et2MeSiH (1 eq), PhNCO (0.5 eq),
C6H6, 80°, 1 h
EtMe2SiH, (Ph3P)3RhCl (0.1 mol%),
C6H6, 60°, 12 h
PhMe2SiH, (Ph3P)3RhCl (0.1 mol%),
C6H6, 60°, 1 h
Et3SiH, (Ph3P)3RhCl (0.1 mol%),
100°, 1 min
(n-Pr)3SiH, (Ph3P)3RhCl (0.5 mol%),
N H
+
(90)
O
OMe
OMe
OMe
O
O
Et3Si
(31.6)
II
OMe
(78)
(80)
OMe
OSiEt3
(n-Pr)3Si
(90)
+
O
TMS
(23)
(26)
O
O
Product(s) and Yield(s) (%)
OMe (33) +
Et3Si
OMe
O
EtMe2Si
PhMe2Si
II (54)
Ph
+
O
TMS
OMe
OSi(Pr-n)3
I (42)
Et3SiH, H2PtCl6 (0.5 mol%)
I
I (22) +
I (96)
O
TMSH, H2PtCl6 (0.5 mol%)
C6H6, rt, 4 h
PMHS-Pd nanocomposite,
CD3CN, DMI (0.5 eq), 70°, 5 h
Cl3SiH (2 eq), CoCl2 (0.175 eq),
Conditions
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS
OMe
OMe
(38.9)
(4)
475
466
466
466
467
467
467
219
451
Refs.
510
C4
O OMe
Unsaturated Ester
(89) (68) (79) (0)
10 h 47 h 47 h 68 h
[Rh(cod)(PPh2Me)2]OTf [Rh(cod)(dppb)]OTf Rh4(CO)12 None
O
(90) (93) (96) (73) (96) (96) (86) (94) (99) (85) (82) (82) (45) (43) (0)
Time 3h 3h 13 h 5h 15 h 13 h 13 h 12 h 6h 4h 12 h 14 h 15 h 61 h 24 h
Ph 4-ClC6H4 4-BrC6H4 4-MeOC6H4 4-MeC6H4 3-MeC6H4 2-MeC6H4 2-ClC6H4 1-C10H7 2-C4H3O p-Ts Bz Bn c-C3H5 c-C6H11
O
R
CH2Cl2, 45°
[Rh(cod){P(OPh)3}2]OTf (1 mol%), N H
(95)
14 h
[Rh(cod)(PPh3)2]OTf
O
(90)
3h
Et2MeSiH (1 eq), RNCO (0.5 eq),
(86)
21 h
N H
[Rh(cod){P(OPh)3}2]OTf
R
Ph
O
[Rh(cod){P(OPh)3}2]OTf
PhNCO (0.5 eq), CH2Cl2, rt Time Catalyst
Et2MeSiH (1 eq), catalyst (1 mol%),
Conditions
OMe
OMe
Product(s) and Yield(s) (%)
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)
475
475
Refs.
511 (68) (49) (47) (20:1
(69) syn:anti = 23:1
(15) syn:anti = 15:1
6.6:1
O
O
OMe
BnOCH2
I
O
OH
Ph
OH
OMe
OMe
OH
O
O
I + II
R
Ph
Ph
OH
OH
R
RCHO, 97 (7.5 mol%), rt, 24 h
Et2MeSiH, [Ir(cod)Cl]2 (2.5 mol%),
1-naphthaldehyde, CH2Cl2, rt, 16 h
Me-DuPHOS (5.5 mol%),
Cl2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),
(E)-PhCH=CHCHO, CH2Cl2, rt, 16 h
Me-DuPHOS (5.5 mol%),
Cl2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),
CH2Cl2, rt, 16 h
Me-DuPHOS (5.5 mol%), PhCHO,
Cl2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),
CH2Cl2, rt, 16 h
Me-DuPHOS (5.5 mol%), i-PrCHO,
Cl2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),
601
762
762
762
762
512
C5
C4
O
O
OEt
OMe
Unsaturated Ester
70°, 12 h
ClMe2SiH, (Ph3P)3RhCl,
reflux, 12 h
EtMe2SiH, (Ph3P)3RhCl,
80°, 2 h
PhMe2SiH, (Ph3P)3RhCl,
CD3CN, DMI (0.5 eq), 70°, 5 h
Cl3SiH (2 eq), CoCl2 (0.175 eq),
CD3CN, DMI (0.5 eq), 80°, 10 h
PhMe2SiH (2 eq), CoCl2 (0.175 eq),
RhCl3•3H2O (0.009 mol%), acetone, rt
TMSH (1.3 eq), (24)
I
OEt
OEt
SiMe2Cl
O
EtMe2Si
Me2PhSi
I (70)
O
OTMS
O
O
(65)
OEt
OEt
(85)
O
III
OMe
50:50 (14)
50:50 (10)
II I:II
(83)
(85)
(62)
20 h
BnCH2
R
OH
(80)
OMe
OMe
+
(E)-PhCH=CH 20 h
O
I
O
I + II
R
OH +
Product(s) and Yield(s) (%)
Time
R
2. H3O+
RCHO, DCE, 20°
1. PhSiH3 (2 eq), Co(dpm)2 (0.05 mol%),
Conditions
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)
R III
OH
466
466
466
451
451
473
475
Refs.
513
O OMe
acetone, rt
RhCl3•3 H2O (0.009 mol%),
TMSH (1.3 eq),
2. MeOH, rt
1. TMSH, H2PtCl6 (0.5 mol%), 60°, 3 h
rt, 72 h
(Ph3P)4Pd (0.02 eq), PPh3 (0.09 eq),
Ph2SiD2 (1.2 eq), ZnCl2 (1.74 eq), D
OMe
+
OMe
OMe
OTMS
O
O
O
+
O OMe
(54)
TMS
CO2Me
CO2Me
(89)
(28)
(90)
(17)
473
467
436
514
C5
O
OMe
OMe
O
Unsaturated Ester
TMSH (1.3 eq), RhCl3•3 H2O O (0.009 mol%), , rt R1 R2
THF, reflux, 20 h
Mo(CO)6 (3-5 mol%),
PhSiH3 (1.3-1.5 eq),
CH2Cl2, 80°, 24 h
[Rh(cod){P(OPh)3}2]OTf (1 mol%),
Et2MeSiH (1 eq), PhNCO (0.5 eq), N H
R2
R1
O
O
OMe
OMe
OTMS
O
O
O
(61)
5h
2-ClC6H4 (53)
(95)
14 h
2-MeC6H4
12 h
(84)
14 h
3-MeC6H4
p-Ts
(95)
12 h
4-MeC6H4
(83)
(92)
14 h
4-MeOC6H4
4h
(91)
13 h
4-BrC6H4
2-C4H3O
(80)
4h
15 h
(87)
13 h
4-ClC6H4
1-C10H7
(88)
Time
N H
O
Ph
Ph
Ar
Ar
CH2Cl2, 45°
[Rh(cod){P(OPh)3}2]OTf (1 mol%),
Et2MeSiH (1 eq), ArNCO (0.5 eq),
Conditions
(78) H
(66)
(91)
(95) —CH2CH(Me)(CH2)3—
Me Me
Et
R2 Me
Me
(26)
R1
(90)
OMe
OMe
Product(s) and Yield(s) (%)
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)
473
450
475
475
Refs.
515
O
O
O
OMe
EtMe2SiH, (Ph3P)3RhCl, C6H6, 70°, 12 h
PhMe2SiH, (Ph3P)3RhCl, 60°, 2 h
100°, 1 min
(n-Pr)3SiH, (Ph3P)3RhCl (0.5 mol%),
Et3SiH, (Ph3P)3RhCl, C6H6, 70°, 2 h
(P h3P)4RhH (0.3 mol%), CH2Cl2, rt, 1.5 h
(EtO)3SiH (1.1 eq),
CH 2Cl2, rt, 12 h
(P h3P)4RhH (0.3 mol%),
(EtO)3SiH (1.1 eq),
RhCl 3•3H2O (0.009 mol%), acetone, rt
TMSH (1.3 eq),
O
OMe
OSiMe2Et
OMe
OSiMe2Ph
OMe
OSi(Pr-n)3
OMe
OSiEt3
OMe
(86)
(71)
(70)
+
+
+
(34)
(91)
(74)
(85)
O
OSi(OEt)3
O
OSi(OEt)3
TMSO
OMe
OSiMe2Et
OMe
(6)
(24)
(6)
OSiMe2Ph
OMe
OSiEt3
466
466
467
466
374
374
473
516
C6
C5
O
O
O OMe
OMe
OEt
Unsaturated Ester
100°, 1 min
n-Pr3SiH, (Ph3P)3RhCl (0.5 mol%),
TMSH, H2PtCl6 (0.5 mol%)
2. MeOH, rt
100°, 1 min
1. (n-Pr)3SiH, (Ph3P)3RhCl (0.5 mol%),
2. MeOH, rt
100°, 1 min
1. Et3SiH, (Ph3P)3RhCl (0.5 mol%),
2. MeOH, rt
60°, 10 min
1. TMSH, (Ph3P)3RhCl (0.5 mol%),
Et3SiH, (Ph3P)3RhCl, C6H6, 70°, 3 h
Conditions
Et3Si
OEt
OMe
OMe
OSi(Pr-n)3
+
O
OMe
OSi(Pr-n)3
OMe
OSiEt3
OMe
OTMS
O +
O
O
(25)
OMe
(28)
(3)
(8.6)
OEt
OSiEt3
OMe
TMS
TMS
Et3Si
CO2Me
CO2Me
+
+
(75.4)
(56)
(73.5)
(85.6)
(77)
(52)
Product(s) and Yield(s) (%)
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)
467
467
467
467
467
466
Refs.
517
O
CN
O
OEt
OMe
OEt
OEt
O
O
Et3SiH (1 eq), TFA (3 eq), 0°, 25:1
21:1
—
4.3:1
11:1
dr
OH
CO2Me
(47)
2h
(EtO)3Si
OSiEt3
(0)
6h
Et3SiH (2.1 eq), (Ph3P)4RhCl (1 mol%),
(8)
15 h
Ph2ClSi
O
OH
CO2Me
O
PhMeClSi
H
(74)
O
1h
Time
N
S
MeCl2Si
R3Si
Me-DuPHOS (5 mol %), C6H6, rt
R3SiH, [Rh(cod)Cl]2 (2.5 mol%),
Me-DuPHOS (5 mol%), C6H6, rt, 4 h
MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),
CH2Cl2, rt, 1.5 h
Et3SiH (3.15 eq), TFA (19.5 eq),
R
471
471
474
474
468
522
C9
O
O
H
OPh
O
OMe
Unsaturated Ester
RCHO (0.2 eq), rt, 12 h R
Et2MeSiH (0.35 eq), [Rh(cod){(R)-BINAP}] BF4 (5 mol%),
1. R3SiH (0.5 eq), [Rh(cod){(R)-BINAP}] BF4 (5 mol%), CH3CH2CHO (2.0 eq) 2. H3O+ R3Si Et2MeSi PhMe2Si (EtO)Me2Si
1. EtMe2SiH (1.0 eq), [Rh(cod)Cl]2 (2.5 mol%), CH3CH2CHO (0.83 eq), (R)-BINAP (6.5 mol%), rt, 24 h 2. H3O+
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),
Conditions
I
OH
PhO
(0)
I (23) (18) O
I + II
er I
O
O II
O
(6) dr = 4.6:1, er = 94:6
PhO
er II 91:9 90:10 89:11
+
II
(73) syn:anti = 7:1, ee syn = 81%
(90) syn:anti = 3:1, ee syn = 75%
(54) syn:anti = 6:1, ee syn = 71%
(86) syn:anti = 6:1, ee syn = 83%
—
91:9 90:10
R
OH
II (42) (48) (29)
(46) dr = 4.6:1, er = 94:6
PhO
O
+
OSiEt3 CO2Me
I + II (68), I:II = 2.5:1
I
OSiEt3 CO2Me
Product(s) and Yield(s) (%)
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)
470
470
470
471
Refs.
523
C10
O
O
O
O
O
OMe
H
O OPh
OC6H11-c
O
O
OMe
CH3CH2CHO (0.83 eq), rt, 48 h
(S)-BINAP (6.5 mol%),
Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),
Mo(CO)6 (3-5 mol%), THF, reflux, 35 h
PhSiH3 (1.3-1.5 eq),
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),
I
O
O
III
+
+
O
O
O
O
II
I:II:III:IV = 2:5.4:2:1
I + II + III + IV (65)
CO2Me
OSiEt3
CO2Me
OSiEt3
PhO
O
O
I (60)
I O
OMe
OH
OC6H11-c
O
IV
CO2Me
OSiEt3
CO2Me
OSiEt3
(76) syn:anti = 4.3:1, ee syn = 88%
(100)
(68)
I + II + III + IV (81), I:II:III:IV = 5.4:4:2:1
+
O
O
470
450
471
471
471
471
524
C11
C10
n-Pr
Ph
O
O
O
O
O
O
O
H
H
O
OPh
O
O
O
OMe
OMe
O
OMe
Unsaturated Ester
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),
Me-DuPHOS (5 mol%), C6H6, rt, 15 h
MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),
Me-DuPHOS (5 mol%), C6H6, rt, 4 h
MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),
MeC6H5, 20 min
PhSiH3 (1.5 eq), [(Ph3P)CuH]6 (5 mol%),
rt, 48 h
(Ph3P)4Pd (0.02 eq), PPh3 (0.05 eq),
Ph2SiH2 (1.7 eq), ZnCl2 (0.76 eq),
CH3CH2CHO (0.83 eq), rt, 48 h
(S)-BINAP (6.5 mol%),
Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),
Conditions
O
I
O
OH
OMe
OH
(91) dr > 25:1
(88)
(81)
(50) dr = 23:1
O
(80)
(52) syn:anti = 3.9:1, ee syn = 88%
CO2Me
OSiEt3
O
OMe
OH
O
O
Et3SiO
n-Pr
I (95)
Ph
PhO
O
Product(s) and Yield(s) (%)
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)
471
471
474
474
447
436
470
Refs.
525
C12
Ph
O
O
O
O
O
O
O
O OEt
OPh
H OMe
Me-DuPHOS (5 mol%), C6H6, rt, 15 h
MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),
Me-DuPHOS (5 mol%), C6H6, rt, 15 h
MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),
CD3CN, DMI (0.5 eq), 70°, 5 h
Cl3SiH (2 eq), CoCl2 (0.175 eq),
DMA, 0° to rt, 4.5 h
PPh3 (20 mol%), TBAF (10 mol%),
PhMe2SiH (1.2 eq), CuCl (20 mol%),
DMI, rt, 5 h
PhMe2SiH (2 eq), CuCl (x eq),
CH3CH2CHO (0.83 eq), rt, 48 h
(S)-BINAP (6.5 mol%),
Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%), I
I (50)
I (54)
Ph
PhO
O
I
O OEt
OH
I (69) dr = 1:20
CO2Me
OSiEt3
O OH
(74)
(76) dr > 25:1
(0)
0.1
OH
(86)
0.2
O
(90)
(96)
0.5
1
x
(0)
(61) dr = 1.5:1
474
474
451
444
445
470
471
471
526
C13
C12
Ph
Ph
Ph
Ph
Et
O
O
O
OMe
O
OMe
OEt
OEt
OEt
OPr-i
O
O
H
O
CN
O
Unsaturated Ester Conditions
MeC6H5, rt, 4 h
NaOBu-t (0.1 mol%), t-BuOH (12 eq),
PMHS (12 eq), 209 (2 mol%),
MeC6H5, rt, 1 h
NaOBu-t (0.1 mol%), t-BuOH (4 eq),
PMHS (4 eq), 209 (0.3 mol%),
MeC6H5, rt, 1 h
NaOBu-t (1.8 mol%), t-BuOH (4 eq),
PMHS (4 eq), 209 (0.3 mol%),
MeC6H5, rt, 1 h
NaOBu-t (0.1 mol%), t-BuOH (4 eq),
PMHS (4 eq), 209 (0.3 mol%),
reflux, 24 h
Mo(CO)6 (3-5 mol%), THF,
PhSiH3 (1.3-1.5 eq),
50°, 16 h
(Ph3P)3RhCl (1 mol%), MeC6H5,
Et3SiH (2.1 eq),
50°, 16 h
(Ph3P)3RhCl (1 mol%), MeC6H5,
Et3SiH (2.1 eq),
Ph
Ph
Et
I (88)
Ph
Ph
O
O
O
O
CN
I
I
CO2Me
OEt
OEt
OEt
OPr-i
OMe
OSiEt3
O
+
(93) dr = 1.5:1
(97)
(91)
(90)
(91)
I + II (54), I:II = 2:1
OSiEt3
II
OSiEt3
Product(s) and Yield(s) (%)
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)
CO2Me
454
454
454
454
450
471
471
Refs.
527
C15
C14
Ph
n-C6H13
BnO
O H
O
O
O
OPh
O
OPr-i
OMe
OC6H11-c
H
O
O
OPh
THF, reflux, 30 h
Mo(CO)6 (3-5 mol%),
PhSiH3 (1.3-1.5 eq),
CH3CH2CHO (0.83 eq), rt, 48 h
(S)-BINAP (6.5 mol%),
Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),
CH3CH2CHO (0.83 eq), rt, 48 h
(S)-BINAP (6.5 mol%),
Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),
MePh, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),
MePh, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),
MePh, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),
+ BnO
I BnO
CO2Me
+
+
II
I:II:III:IV = 1.7:1.5:1:1
Ph
n-C6H13
PhO
O
PhO
I
O
+
CO2Pr-i
OC6H11-c
471
471
471
(75)
450
470
(30) syn:anti = 4.4:1, —% ee syn 470
II
OSiEt3
CO2Me
(54) syn:anti = 4.2:1, 88% ee syn
OH
I + II (59), I:II = 1:2
CO2Pr-i
OH
O
OSiEt3
IV
OSiEt3
CO2Me
BnO
OSiEt3
I + II + III + IV (81),
III
OSiEt3
CO2Me
I + II + III + IV (72), I:II:III:IV = 1.2:1:1.2:1.7
BnO
OSiEt3
528
C19
C18
C16
EtO
Ph
TBSO
O
O
OEt Sn(Bu3-n)3
O
CO2Me
Ph
OC12H25-n
O
CH2Cl2, –78°, 1 h
Et3SiH (10 eq), TMSOTf (2 eq),
CH3CH2CHO (0.83 eq), rt, 48 h
(S)-BINAP (6.5 mol%),
[Rh(cod)Cl]2 (5 mol%),
Et2MeSiH (5 eq),
CH3CH2CHO (0.83 eq), rt, 48 h
(S)-BINAP (6.5 mol%),
[Rh(cod)Cl]2 (5 mol%),
Et2MeSiH (5 eq),
MeC6H5, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),
DMI, rt, 6 h
PhMe2SiH (4 eq), CuCl (2 eq),
Conditions
EtO
Ph
OEt
OH
OH
Sn(Bu3-n)3
O
O
PhO
O
CO2Me
Ph
OC12H25-n
PhO
TBSO
O
O
(72)
(74)
(95)
93% ee syn
(49) syn:anti = 3.9:1,
88% ee syn
(53) syn:anti = 3.8:1,
Product(s) and Yield(s) (%)
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)
OPh
OPh
O
Unsaturated Ester
469
470
470
471
445
Refs.
529
C22
C21
PhS
Ph
Ph
O
O
O
OMe
H OPr-i
Sn(Bu3-n)3
O
O
Sn(Bu-n)3
OMe
(54)
TMSOTf TFA
Ph3Si Ph3Si
CH2Cl2, –78°, 1 h; 0° 1 h; rt, 4 h
Et3SiH (10 eq), TFA (2 eq),
CH2Cl2, –78°, 1 h; 0°, 5 h; rt, 5 d
Et3SiH (10 eq), TMSOTf (2 eq),
CH2Cl2, –78°, 1 h; rt, 5 d
Et3SiH (10 eq), BF3•OEt2 (2 eq),
MePh, 50°, 16 h
Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),
CH2Cl2, –78°, 1 h; 0°, 1 h
I (24)
I (24)
PhS
Ph
Ph
O
I
+ Ph
Ph
OMe
(42)
I + II (68), I:II = 1:2.5
Sn(Bu3-n)3 I
O
(—)
CO2Pr-i
Sn(Bu-n)3
OMe
Sn(Bu-n)3
OMe
OSiEt3
(0) (74)
HOAc
Et3Si
O
(98)
TMSOTf
Et3Si
D
(96)
TFA
Et3SiH (10 eq), DOAc (2 eq),
(71)
BF3•OEt2
O
Et3Si
Acid
Et3Si
R3Si
CH2Cl2, –78°, rt, 4 h
R3SiH (10 eq), acid (2 eq),
O
II
OSiEt3 CO2Pr-i
469
469
469
471
469
469
530
C25
C24
O
O
O
OBn Sn(Bu3-n)3
O
Sn(Bu-n)3
OBn
Unsaturated Ester
CH2Cl2, –78°, 1 h
Et3SiH (10 eq), TFA (2 eq),
CH2Cl2, –78° to rt, 1 h; 0° 1 h
Et3SiH (10 eq), TMSOTf (2 eq),
Conditions
O
O
O
OBn Sn(Bu3-n)3
O
Sn(Bu-n)3
OBn
(64)
(61)
Product(s) and Yield(s) (%)
TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)
469
469
Refs.
531
C5
C4-10
C3-9
i-Pr
i-Pr
n-Pr i-Pr
H
n-Pr
i-Pr
NMe2
n-Pr
H
O
R2 H
R1
R2
N
n-Pr
n-Pr
R1
n-Pr
H
O
R2 H
H
R2
N
R1
R1
O
Unsaturated Amide
R
(80)
24:76 31:69
(78) (72) (93) (68) (75)
1-C10H7 4-MeC6H4 2-C10H7 4-O2NC6H4 4-ClC6H4
36:64
28:72
30:70
I:II
Ph
R
32:68
NMe2
+
(87)
O
R1
R1
R
OH
II
O NMe2
Product(s) and Yield(s) (%)
I + II
RCHO, CH2Cl2, rt, 45 h I
(70)
15 h
Cl3SiH (1.3 eq), (Ph3P)4Pd, (5 mol%),
(100)
4h OH
(100)
1.3 h
R2
1.7 h
Time
Mo(CO)6 (3-5 mol%), THF, reflux
N
(95)
0.2 h
PhSiH3 (1.3-1.5 eq),
(100)
0.2 h
O
(80) (100)
R2
N
1h
O
0.3 h
Time
Mo(CO)6 (3-5 mol%), THF, reflux
PhSiH3 (1.3-1.5 eq),
Conditions
TABLE 18. ORGANOSILANE REDUCTION OF α,β−UNSATURATED AMIDES
763
450
450
Refs.
532
C25
C11
C10
C5-6
Ph
Ph
R1
O
H H H Me Me
H
Me
Me
H
H
NMe2
NHTs
O
Sn(Bu-n)3
O
H
H
NHMe
H
H
O
R2
NMe2
R1
R2
O
Unsaturated Amide
2h 4h 6h 3h 4h 5h 4h
Ph (E)-PhCH=CH BnCH2 Ph (E)-PhCH=CH Ph (E)-PhCH=CH
CH2Cl2, –78°, 1.5 h
Et3SiH (10 eq), TMSOTf (2 eq),
PPh3 (0.019 eq), CHCl3, rt, 10 h
(Ph3P)4Pd (0.011 eq),
Ph2SiH2 (3 eq), ZnCl2 (1.1 eq),
Mo(CO)6 (3-5 mol%), THF, reflux, 4 h
PhSiH3 (1.3-1.5 eq),
PPh3 (0.019 eq), rt, 10 h
(Ph3P)4Pd (0.011 eq),
Ph2SiH2 (1.5 eq), ZnCl2 (1.0 eq),
Time
R3
R3CHO, ClCH2CH2Cl, 20°
PhSiH3 (2 eq), CoX2 (0.05 mol%),
Conditions OH
Ph
O
I (80)
Ph
R3
I
I
NHTs
NMe2
NHMe
—
—
72:28
70:30
70:30
72:28
80:20
Sn(Bu-n)3
O
O
O
(70)
(50)
(68)
(72)
(90)
(96)
(95)
I:II
NMe2 +
I + II
R1
R2
O
(41)
(78)
+
(14)
(31)
(12)
(10)
(trace)
O R2 R1
(trace)
(3)
III
OH
(78)
R3
O
II
NHTs
R3
Sn(Bu-n)3
O
NMe2 +
Product(s) and Yield(s) (%)
TABLE 18. ORGANOSILANE REDUCTION OF α,β−UNSATURATED AMIDES (Continued)
III
(0.5)
OH
469
436
450
436
478
Refs.
533
C16
C9
C8
C6
C5
C3-4
H H H Me
H
Me
Me
H
Fe
H
H
Ph
H
H
CN
CN
CN
CN
E:Z = 1:1
CN
R2
R2
CN
R1
R1
CN
Unsaturated Nitrile
12 h 5h 12 h
20° 70° 20° 20°
dpm acac dpm acac
Et3SiH (2 eq), TFA, rt, 3 h
PMHS-Pd nanocomposite, C6H6, rt, 5 h
Mo(CO)6 (3-5 mol%), THF, reflux, 12 h
PhSiH3 (1.3-1.5 eq),
rt, 72 h
(Ph3P)4Pd (0.013 eq), PPh3 (0.05 eq),
Ph2SiH2 (1.25 eq), ZnCl2 (0.66 eq),
Mo(CO)6 (3-5 mol%), THF, reflux, 4.5 h
PhSiH3 (1.3-1.5 eq),
Mo(CO)6 (3-5 mol%), THF, reflux, 9 h
PhSiH3 (1.3-1.5 eq),
Mo(CO)6 (3-5 mol%), THF, reflux, 12 h
PhSiH3 (1.3-1.5 eq),
24 h
20°
acac
24 h
3h
70°
acac
PhCHO, ClCH2CH2Cl Temp Time X
PhSiH3 (2 eq), CoX2 (0.05 mol%),
Conditions
I
Fe
I (90)
I (90)
Ph
Ph
I
OH CN
CN
CN
CN
R1
R2
(5) (31)
(92) (60)
CN
(83)
CN
(49)
CN
(100)
(0)
(2) (25)
(72)
(3)
(93)
(42)
II (5)
I
Ph
(70)
+ OH
(100)
II
Product(s) and Yield(s) (%)
TABLE 19. ORGANOSILANE REDUCTION OF α,β−UNSATURATED NITRILES
179
219
450
436
450
450
450
478
Refs.
534
C7
C6-8
C6
C5
O
O R1
OMe
OMe
O
O
OMe
Et3SiH, TFA, 55°, 15 h
TMSOTf (0.01 eq), CH2Cl2, 0°, 30 min
TMSH (1.1 eq),
Et3SiH, TFA, rt
I2SiH2 (3 eq), CHCl3, 22°, 12 h
CH2Cl2, 0°, 30 min
TMSH (1.1 eq), TMSOTf (0.01 eq),
2. I2
1. I2SiH2 (2 eq), CHCl3, 22°, 30 min
I2SiH2 (2 eq), CHCl3, 22°, 30 min
I2SiH2 (2 eq), CHCl3, 22°, 30 min
Conditions
I
(—)
S
OMe
I
OSiEt3
(100)a
(—)
CF3O2C (—)
(45)
OCHR1R2 + R1R2CHO
+
(100)
(100)
OCHR1R2
OMe
(100)
(100)
+ CF3O2C
HO
I
I (99)
I
I
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS
2 O R R1,R2 = H, H; H, Me; Me,Me
O
OMe
S
OMe
OEt
OEt
MeO
O
MeO
Acetal/Ketal
(—)
764
260
480
OCHR1R2
O2CCF3
358
480
358
358
358
Refs.
535
C8
O
O
O
MeO
HO
O
OH
O OH HO
OH
OMe
O
OMe
OH
O
O
MeO OMe
HO HO
HO
CH2Cl2, –78°, 15 min
Ph2SiH2 (1.5 eq), TiCl4 (1.2 eq),
I2SiH2 (3 eq), CHCl3, 22°, 24 h
CH2Cl2, reflux, 4 h
Et3SiH (1.1 eq), Nafion®-H,
I2SiH2 (2 eq), CHCl3, 22°, 2 h
BF3•OEt2 (1.1 eq), 0°, 10 min
2. Et3SiH (1.5 eq),
1. i-Bu2AlH, hexanes, MeC6H5, –78°
TFA (12 eq), 0° to rt, 16 h
Et3SiH (30 eq), BF3•OEt2 (30 eq),
Et3SiH, TMSOTf, MeCN
I
O HO
O
OH
OH
O
(98)
(70)
(50)
OH
(91.7)
(90)
(50)
O
O
MeO OMe
OMe
I
HO
HO HO
HO
(82)
492
358
335
358
510
483
518
536
C8
O
O
O
O
O
O O
O
O Et3SiH, HOTf
CH2Cl2, –78°
Et3SiH (1.2 eq), SnCl4 (1.2 eq),
CH2Cl2, –78°, 15 min
Et3SiH (1.2 eq), TiCl4 (1.2 eq),
CH2Cl2, –78°
Et3SiH (1.5 eq), TiCl4 (1.2 eq),
CH2Cl2, –78°, 15 min
Ph2SiH2 (1.5 eq), TiCl4 (1.2 eq),
CH2Cl2, –78°
Et3SiH (1.5 eq), TiCl4 (1.2 eq),
Conditions
I
O +
O
IV
O
II
O
II
O
OH
OH
OH
OH
(51) single diastereomer
I + II (71), I:II = 63:36
OH
+
I + II (76), I:II = 7:93
OH
I + II (72), I:II = 76:24
I
O
+
II
O
I + II + III + IV (61),
OH
+
I:II:III:IV = 42.6:0.8:48.7:7.9
III
O
OH
I + II (82), I:II = 1:99
+
I
O
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
499
495
495
495
495
495
Refs.
537
C8-12
R2
R1
H H H H H Me H H H H Me
Ph
Ph
Ph
Ph
4-ClC6H4
Ph
3-MeOC6H4
3-MeOC6H4
4-MeC6H4
BnCH2
BnCH2
R2 H
—(CH2)5—
c-C6H11
R1
O
O
(93)
(81)
(70)
Bn
(80)
(93)
Bn
Bn
(86)
Bn
(86)
(80)
c-C6H11
Bn
(86)
allyl
(83)
(87)
n-C5H11
Bn
(82)
Bn
allyl
(87)
R2
Bn
R1
OR3
Bn
R3
Sn(OTf)2, MeCN, –20°, 3-6 h
TBSH (1.4 eq), R3OTMS (3 eq), 501
538
C9
C8
Ph
O
O
OMe
OMe
endo:exo = 40:60
OEt
OEt
OMe
OMe
O
O
CH2Cl2, reflux, 2 h
Et3SiH (1.1 eq), Nafion®-H,
CH2Cl2, 0°, 30 min; 29°, 16 h
Et3SiH (1.1 eq), TMSOTf (0.01 eq),
CH2Cl2, 0°, 30 min
TMSH (1.1 eq), TMSOTf (0.01 eq),
CH2Cl2, reflux, 2 h
Et3SiH (1.1 eq), Nafion®-H,
Et3SiH (1.2 eq), TFA (30 eq), 50°, 8-10 h
CH2Cl2, 0° to rt, 24 h
Et3SiH (10 eq), BF3•OEt2 (10 eq),
CH2Cl2, 0° to rt, 24 h
Et3SiH (10 eq), BF3•OEt2 (10 eq),
Conditions
I (96)
I (90)
Ph
+
(96)
(99)
(21)
(75)
+
I + II (85), I:II = 40:60
OEt
OH
OH
OMe
OMe I
O
I
O
O
II
O OH
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
(45)
335
480
480
335
327
485
485
Refs.
539
C9-12
C9-10
C9
Ph
R
Ph
R
NEt2
(91)
(89)
Br
Ac
Ac
O MeO
(77)
(82)
AcBr (2.2 eq), CH2Cl2, rt, 3 h
Et3SiH (1.56 eq), SnBr2 (0.056 mol%),
CH2Cl2, 0° to rt, 36 h
Et2NSiHMe2 (1.2 eq), TiCl4 (0.2 eq),
O
MeO OMe
(96)
Et
6
2. Ac2O (12 eq), rt, 24 h
AcO MeO
MeO
MeO
—(CH2)5—
Me
Et
O
TFA (12 eq), 0°
1. Et3SiH (30 eq), BF3•OEt2 (30 eq),
TFA (12 eq), 0° to rt, 16 h
Et3SiH (30 eq), BF3•OEt2 (30 eq),
I (97)
Et3SiH, FSO3H, TMSNHCONHTMS
—(CH2)4—
R2
Me
MeO
R1
OR2
OR1
OMe
MeO
MeO O
OMe
MeO OMe
OMe
O
MeO
O
I (76)
I (46)
I (93)
Et3SiH, FSO3H, MeC(OTMS)=NHTMS
MeCN, reflux
Et3SiH (4 eq), TCNE (0.3 eq),
CH2Cl2, rt, 10 min
Et3SiH (5 eq), Sn-mont,
Bn
Ph
R (31)
(79)
(81)
(95)
506
359
483
483
487
487
500
353
540
C9-20
C9-13
Cl Br Cl Br Cl Br Cl
Ph
3-MeOC6H4
3-MeOC6H4
4-MeC6H4
4-MeC6H4
4-ClC6H4
Cl Br
2-C10H7
2-C10H7
R
Br
1-C10H7
CO2Me
0
0
0
0
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
3h
5h
1h
2h
7h
5h
2h
12 h
3h
3h
2h
3h
3h
3h
Time
CH2Cl2, –78° to rt, 4 h
Et3SiH, BF3•OEt2,
Cl
1-C10H7
R4
Br
4-BrC6H4
2
Cl
4-BrC6H4
O
Br
4-ClC6H4
R3
X
Temp
SnX2 (0.056 mol%), AcBr (2.2 eq), CH2Cl2
Ph
OMe
Et3SiH (1.56 eq),
Ar
R1
HO
Ar
OMe
Conditions
R1 R
Ar
2
O
R4
R3
CO2Me
(94)
(91)
(96)
(92)
(97)
(92)
(87)
(79)
(86)
(89)
(99)
(97)
(89)
(76)
Br
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
512
506
Refs.
541
C9-16
R
1
Me
Me
Ph3SiH (1 eq), TiCl4 (1.2 eq), R1
7:1 13:1 63:1 16:1 9:1
Ph Me Ph Ph
Me Ph Et i-Pr
10:1
Et
Me
trans:cis
H
Me
O
Me
CH2Cl2, –78°, 5 min
S
(40)
Ph
R2
OH
S R2
(48)
—(CH2)5— Ph
(79)
Ph
(51)
(43)
(61)
R1
O
S
Me
—(CH2)5—
Me
H
Me
H
—(CH2)5—
Me
Me
Me
Me
Me
H
Me
Me
R4
R3
R2
R1
(82)
(81)
(72)
(83)
(63)
(70)
S R2
520
542
C10
Ph
Ph
Ph
O
O
HO
O
O
O
O
O
O
O
OEt
EtO
O
OH
OH
OMe
O O
CHO
Et3SiH, BF3•OEt2, –45°, 5 min
THF, 60°, 48 h
(Ph3P)3RhCl (0.025 mol%),
PhSiH3 (4 eq),
THF, rt, 48 h
(Ph3P)3RhCl (0.025 mol%),
PhSiH3 (3 eq),
Et3SiH, HOTf
I2SiH2 (1.2 eq), CH2Cl2, rt, 4 h
I2SiH2 (1.2 eq), CH2Cl2, rt, 4 h
HCl, CH2Cl2, rt, 1 h
Et3SiH (2 eq), AlCl3 (1 eq),
CH2Cl2, rt, 1 h
Et3SiH (2 eq), AlCl3 (1 eq),
HCl, 20°, 1 h
Et3SiH (2 eq), AlCl3 (1 eq),
50°, 8-10 h
Et3SiH (1.2 eq), TFA (30 eq),
Conditions
Ph
Ph
Ph
O
I
I (50)
I (93)
I (93)
OEt
O
O
O
O
I
O
OH
(89)
(75)
OH
OH
(39)b
I
CHO
(86)
(91)
(81)
(94)
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
510
493
493
499
505
505
136
136
146
327
Refs.
543
Bn
O
Br
Ph
O
O
OMe
MeO
MeO
O
O
OMe
OMe
O
O O
OMe
OMe
I2SiH2 (2 eq), CHCl3, 22°, 2 min
I2SiH2 (1 eq), CHCl3, 0°, 60 min
THF, rt, 48 h
(Ph3P)3RhCl (0.025 mol%),
PhSiH3 (3 eq),
2. LiAlH4, THF, rt, 2.5 h
CH2Cl2, rt, 2.5 h
1. Et3SiH, SnBr2-AcBr,
C6H6, reflux, 0.5 h
2. (n-Bu)3SnH, AIBN,
CH2Cl2, rt, 2.5 h
1. Et3SiH, SnBr2-AcBr,
I2SiH2 (2 eq), CHCl3, 0°, 99:1
R (92)
+
(100)
R
CH2OBn R3O
H
Ph
O I I:II
H
99:1
R1
HO
(91.2)
(59)
CH2Cl2, –78°, 3 min
Et3SiH (4 eq), TiCl4 (1.2 eq),
Ph
OMe
I + II
R
CH2Cl2, reflux, 2 h
Et3SiH (1.1 eq), Nafion®-H,
(13)
O
H
Product(s) and Yield(s) (%)
CO2Et
O
OMe
O
O
R3O R 3O
R3O
H
Ph
MeO
Conditions
H
O II
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
Pr-i
R H
(11)
485
483
489
335
Refs.
545
MeO
Ph
H
MeO
HO
O
O H
HO
MeO MeO
O I
OMe
OMe
O
OMe
OH
OMe
H
O O
H
H
O
OMe
OMe O
MeCN, reflux
Et3SiH (4 eq), TCNE (0.3 eq),
Et3SiH, HOTf
Et3SiH, HOTf
Et3SiH, TFA, 70°, 8 h
TFA (12 eq), 0° to rt, 16 h
Et3SiH (30 eq), BF3•OEt2 (30 eq),
MeO
Ph
O
O H H
H
O
MeO MeO
O O
O O
I
OMe
OMe
H
OMe O
(65)
(70)
(59)
(82)
(100)
500
499
499
515
483
546
C11
O
Br
Ph
Ph
O
O
O
O
OH
Ph
O
O
O
Ph
OEt
OEt
Ph
Ph
O
OMe
OMe
CH2Cl2, –78° to 0°
Et3SiH (3 eq), TFA (3 eq),
I2SiH2 (2 eq), CHCl3, 0°, 99:1
cis:trans
HO
(98)
(94)
(97)
(65)
(67)
(91)
(92)
(9)
510
479
295
295
496
556
C18-20
C18
C17
O
MeO
Ph
O
H
O
H
O
O
O
OR
9
R
O
O
N
O
OBn
H
H OMe
OMe
R = TMS
H
OH Cl
O
OR
O OMe H
H
O
O
OMe OH
O
RO
RO
Et2O:CH2Cl2 (1:1), rt, 12 h
PMHS, AlCl3 (1 eq),
CH2Cl2, –70°, 45 min
Et3SiH (8 eq), TMSOTf (2 eq),
Et3SiH (1.1 eq), TFA, rt, 18 h
Et3SiH, TMSOTf, CH2Cl2, 0°
CH2Cl2, –78°, 15 h
Et3SiH (4 eq), TiCl4 (1.2 eq),
MeCN, rt, 16 h
Et3SiH (5 eq), TMSOTf (5 eq),
Conditions
H
H
HO
OMe
OMe
O
HO
HO
O H
H
Cl
R
O
9
H
N
OH
O
OH
O (70)
O
OBn
HO
(69)
+ HO
(70)
(69)
O (1)
(82)
CO2Me
N3
R
OMe
OMe
(65)
H
(89)
O
H
OBn
(94)
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
OBn
496
339
486
481
488
503
Refs.
557
C18-28
C18-19
Ph
Ph
Ph
H
O
O
O
O
O
O
O
H
TBSO
TBSO
Ph
O
O
O
OR
O
OR
O
OR
O
OAc
O
R
OR
OMe
OR
OMe
OR
OMe
OH
CN
OH
NHAc
OMe
CH2Cl2, rt, 2-4 h
Et3SiH (5 eq), TFA (5 eq),
CH2Cl2, rt, 2-4 h
Et3SiH (5 eq), TFA (5 eq),
CH2Cl2, rt, 2-4 h
Et3SiH (5 eq), TFA (5 eq),
Et3SiH, BF3•OEt2, –78°, 30 min
–78°, 30 min
2. Et3SiH (1.5 eq), BF3•OEt2 (1.1 eq),
MeC6H5, –78°
1. (i-Bu)2AlH, hexanes,
CH2Cl2, rt, 2-4 h
Et3SiH (5 eq), TFA (5 eq),
TBSO
HO
BnO
HO
BnO
HO
BnO
H
H
TBSO
HO
BnO
OR
O
OR
O
OR
O
O
O
OAc
O
OR
OMe
OR
OMe
OR
OMe
R
CN
NHAc
OMe
SPh
CN
H
R
Bn
Ac
R
Bn
Ac
R
Bn
Ac
R
(60)
(75)
(81)
(75)
(94)
(81)
(98)
(80)
(95)
(—)
(—)
494
494
494
510
510
494
558
C19
OR
OMe
RO RO
RO
RO
O
OR OMe
R = TMS
R = TMS
Et3SiH (5 eq), TMSOTf (5 eq),
MeCN, rt, 16 h
Et3SiH (5 eq), TMSOTf (5 eq),
MeCN, rt, 16 h
HO
HO
HO
O
RO
OR
HO
R = TMS
MeCN, rt, 16 h
RO
OR
OMe
Et3SiH (5 eq), TMSOTf (5 eq),
OH
OH
O
OH
O
(72)
OH O
OH
OH
OH
HO O
OH
HO O
O HO HO OH HO
O
MeCN, rt, 16 h
Et3SiH (5 eq), TMSOTf (5 eq),
HO
RO
R = TMS
R = TMS
MeCN, rt, 16 h
Et3SiH (5 eq), TMSOTf (5 eq),
HO
HO
HO
OMe
OR
R = TMS
MeCN, rt, 16 h
Et3SiH (5 eq), TMSOTf (5 eq),
Conditions
RO
OR
OMe
OR
RO OMe O
OR
RO O
O RO RO
OR
RO
RO
RO
(19)
(78)
+ HO
HO
(100)
(97)
(97)
OH
OH
(9)
OH
+
+
OH
O
+
O OH HO HO HO
HO
Product(s) and Yield(s) (%)
HO
HO
OH O
OH
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
(19)
OH
OH
OH
O OMe
(3)
(19)
503
503
503
503
503
503
Refs.
559
C19-21
Ph
Ph
Ph Ph
Ph
H
R4
H
H
—(CH2)4—
Me
H
R3
Me
R2
Ph
O
Ph
O
CO2Me
Ph
R1
O
O
O
OH
S
R4 R3 R2
R1
O
S
(73) (76) (88)
EtAlCl2 AlCl3 TMSOTf
Ph3Si Ph3Si Ph3Si
Ph
(82)
Et2AlCl
Ph3Si
TiCl4
CH2Cl2, –70°, 45 min
Et3SiH (8 eq), TMSOTf (2 eq),
Et2O:CH2Cl2 (1:1), rt, 12 h
PMHS, AlCl3 (1 eq),
Et3Si
H
S Ph
R1
(53)
(42)
R3
O
CO2Me
R4
OH
OBn
7:1
30:1
34:1
17:1
11:1
18:1
28:1
10:1
82:1
16:1
15:1
trans:cis
(57)
R2
(75)
(79)
(86)
BF3•OEt2
Ph3Si
PhMe2Si TiCl4
(88)
TiCl4
Ph3Si
(70)
(87)
TiCl4
Ph2MeSi TiCl4
(76)
TiCl4
O
Ph3Si
Lewis acid
Ph
S
Ph3Si
R3Si
CH2Cl2, –78°, 5 min
R3SiH (1 eq), Lewis acid (1.2 eq),
(68)
339
496
520
560
C20
Ar
H
O
HO
O
O
O
O
O
O
O
Cl N
Ar = 3-MeO-4-HOC6H3
OH
H
Ar
CO2Me
Ph
Ph
O
OH
Ph
Et3SiH, BF3, Et2O
CH2Cl2, –78°, 45 min; rt, 3 h
Et3SiH (1.1 eq), BF3•OEt2 (1.1 eq),
Et3SiH (1.1 eq), TFA, rt, 18 h
CH2Cl2, –70°, 45 min
Et3SiH (8 eq), TMSOTf (2 eq),
Conditions
Ar
H
O
O
Ph
O H
Ar
CO2Me
Ph
Ph
O (47)
O
+
N
+
H
O
Ar
H
O
Ar
(88)
Cl
(97)
O
O
O (14)
O
(37)
(20)
H
H
H
Ar +
OH
OMe
H
O
Ar
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
O (19)
O
Ar H
766
765
468
339
Refs.
561
C21
H
O
O
OR
O
Ph
OR
O
OBn
Et3SiH, BF3•OEt2, –20°, 24 h O
(48)
MeO
H
O
H
CO2Et
OTBS
R = TMS
OBn
O
I2SiH2 (2 eq), CH2Cl2, rt, 2 h
CH2Cl2, –23°
Et3SiH (5 eq), TiCl4 (3.0 eq),
MeCN, rt, 16 h
Et3SiH (5 eq), TMSOTf (5 eq),
I
Ph
HO
O
EtO2C
EtO2C
H
O
CCl3
OH
H
O
(71)
+
O HO
OMe
+
MeO
(94) α:β = 3:1
OH
OH OH
(65)
OMe
(40)
O
+ Ph
(—)
OBn
MeO
(95)
+
MeO
CO2Et
O OH
O
AcO
O PhMe2SiH, BF3•OEt2
OH OPr-i
O
OH
H
MeO MeO
O
OH
TFA (12 eq), 0° to rt, 16 h
Et3SiH (30 eq), BF3•OEt2 (30 eq),
O
OMe
OMe
MeO
OH
O
OMe OMe O
OH
MeO
CCl3
O RO
EtO2C
EtO2C
AcO
O
MeO MeO
MeO
(5)
(10)
CO2Et
MeO
MeO O
(23)
OMe
505
306
503
767
510
482
562
C23
C22
HO
O
O
O
O
O
Ph
Ph
SPh
OH
CO2Me
O
H
N
H
O
OMe
OMe
S
MeO2C
H
H
O HO H
N
HO
H
TBSO
Me
H
MeO
OH
HN
O
O
H O
OMe 2
CH2Cl2, –78°, 45 min; rt, 3 h
Et3SiH (1.1 eq), BF3•OEt2 (1.1 eq),
–78°, 30 min
2. Et3SiH (1.5 eq), BF3•OEt2 (1.1 eq),
MeC6H5, –78°
1. (i-Bu)2AlH, hexanes,
Et3SiH, TFA
CH2Cl2, MeCN, 0°
Et3SiH, BF3•OEt2,
Et3SiH (2.5 eq), TFA, 0°, 2 h
Conditions
O
O
H
N
O
O
Ph
Ph
O
O
HN
H
SPh
+
H O
OMe
(60)
(70)
N
H
O
H
(58)
OMe O
MeO2C
H
H
O
S
CO2Me
HO
H
TBSO
Me
H
MeO
OH
O
HN
(—)
(83)
HS
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
O (56)
O OMe
765
510
770
769
768
Refs.
563
C27
C24
O
MeO
MeO
OH
H
O
MeO
MeO
H
OAc
HO
MeS
OAc
O Et3SiH, BF3•OEt2, rt, 3 h
–78°; rt, 48 h
BF3•OEt2 (1.5 eq), CH2Cl2,
O
O
O
Et3SiH (4.5 eq),
OH
OH
OAc
OBn
OMe
H
O
BF3•OEt2 (12 eq), CH2Cl2
Et3SiH (13 eq),
BnO
OAc
O
O
OH
OAc
MeS
MeO
O O
O O O
Ph
Ph
O
O H
OBn
OH
OBn
(88)
O
O
(64)
(89)
510
484
495
564
C29
C28
C27
Ph
BnO
OBn
Ph
Ph
BnO
OBn
BnO
OBn
O O BnO
O
O O BnO
O O BnO
O
O
O OMe
O PhthN OMe
OBn
OH
OMe
OBn O
BnO
OBn
OH
OBn
OH
CH2Cl2, rt, 4 h
Et3SiH (12 eq), BF3•OEt2 (2 eq),
–78° 1 h; –10°, 12 h
Et3SiH, BF3•OEt2, CH2Cl2,
CH2Cl2, rt, 4 h
Et3SiH (12 eq), BF3•OEt2 (2 eq),
CH2Cl2, rt, 4 h
Et3SiH (12 eq), BF3•OEt2 (2 eq),
–78° 1 h; –10°, 12 h
Et3SiH, BF3•OEt2, CH2Cl2,
–78° 1 h; –10°, 12 h
Et3SiH, BF3•OEt2, CH2Cl2,
Conditions
HO BnO
BnO
OBn
HO BnO
BnO
HO BnO
BnO
OBn
BnO
OBn
I
OMe
O
OBn
OMe
OBn
OMe
OBn O
BnO
O
OBn
OBn
OBn
PhthN
O
I
O
O
+
+
(85)
BnO
OBn
(59)
(83)
BnO
OBn
(53)
II
O
II
O
OBn
OBn
I + II (81), I:II = 5:1
I + II (76), I:II = 5:1
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
497
508
497
497
508
508
Refs.
565
C35
C34
C32
BnO BnO
BnO BnO
BnO BnO
BzO
O
O O
Ar
OH
O
O
OMe
OBn OBn O
BnO OMe
OBn
BnO
O
OH
OBz Ph
OBn
OBz
O
Ar = 2,6-dichloro-3-pyridinyl
TBDPSO
–5° rt
1 2
ZnBr2 ZnCl2•OEt2
3h
1.5 h
1.5 h
1.5 h
Time
CH2Cl2, 0° to rt, 16 h
Et3SiH (3 eq), TMSOTf (2.25 eq),
CH2Cl2, 0° to rt, 16 h
Et3SiH (3 eq), TMSOTf (2.25 eq),
–78°, 1 h; rt, 3 h
2. Et3SiH, BF3•OEt2, CH2Cl2,
1. PhMgCl (1.5 eq), THF, –78°
Et3SiH, BF3•OEt2, MeCN, –40° to rt
–5°
1
SnCl4
–5°
Temp
2
x
BF3•OEt2
Catalyst
Et3SiH (x eq), catalyst
BnO BnO
BnO BnO
O
O
Ph
O
O
OBn OBn O
BnO
OBn
BnO
O
OBn
O OBz OBz
BnO BnO
BzO
TBDPSO
(80)
(77)
(88)
— 2:1
(68)
(—)
1:5
(—)
2.6:1
α-D:β-D
+
TBDPSO
(30)
(57)
β-D
Ph
Ar
O
O O
Ar
α−D
504
504
771
509
511
566
C37
C36 O
OBn
Et3SiH, TMSOTf
HO
BnO
HO
BnO
HO
BnO
O
OBn
O
OBn
O
OBn
OH OBn
OBn
OBn
OBn
OBn
OBn
Et3SiH, BF3•OEt2, MeCN, 0° to rt
Et3SiH, BF3•OEt2, MeCN, 0° to rt
Et3SiH, BF3•OEt2, MeCN, 0° to rt
BnO
BnO
O
I
O
OBn
I
O
OBn
O
OBn
OBn
OBn
BnO
BnO
O
BnO
O
OBn
OBn OBn BnO
OBn
Et3SiH, TMSOTf
BnO
BnO
OH OBn
OBn
OBn
BnO
Conditions
+
(85)
BnO
+
BnO
I + II (67), I:II = ca. 1:1
OBn
OBn
I + II (76), I:II > 10:1
OBn
OBn
OBn
OBn
(65)
(35)
II
O
OBn
II
O
OBn
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
OBn
OBn
OBn
OBn
507
507
507
519
519
Refs.
567
C38
C37-39
H
O
OBn
OAc
OBz
O
CO2Et
HO
BnO
OH
OAc OAc
OH
OBn
OH
OBn
OBn
OAc
Et3SiH, BF3•OEt2, MeCN, 0° to rt
Et3SiH, BF3•OEt2, MeCN, 0° to rt
BnO
EtO2C
BnO
EtO2C
AcO OAc
O I
OBn
O
OBn
+
BnO EtO2C
(72)
OAc
O II
OBn
(—)
OBn I + II (66), I:II = 3:1
OBn
OBn
OBn
OAc OAc
OH
(80)
(30)
(77)
CO2Me
O
Ph
3-C4H3O
CO2Me H
(87)
2-C4H3O
Ar
OH
O
O
N
O Et3SiH, BF3•OEt2, CH2Cl2, rt, 1 h
OBz
Ar
BnO OBn
O
O OBz BzO
BnO
OBz Et3SiH, BF3•OEt2, MeCN, –40° to rt
CH2Cl2, –78°, 1 h; 10°, 16 h
Et3SiH (2 eq), BF3•OEt2 (2 eq),
O OBz Ar
O
OBz
OH
OBn CO2Et OBn
HO
BnO
O
BnO OBn
AcO
O
HO
BzO
BnO
N
OBn
OBn 507
507
773
509
772
568
C42
C40
C39
O
BnO
O
OAc
O
BnO H
O
OH OBn
O
Ph
OAc
O
OAc
O
H
O H
O
OAc
O
OAc
O
H MeO
AcO
OAc
O
OH OBn
OBn
OBn
BnO
O
O
OBn
OBn
BnO
Ph
Ph
O
AcO
H
O
OAc
H
(CF3CO)2O (3 eq), CH2Cl2, rt, 2-4 h
Et3SiH (5 eq), TFA (5 eq),
H
H O
H O
H OH
Et3SiH, TMSOTf
Et3SiH, TMSOTf
OH
CH2Cl2, 0°
Et3SiH, TMSOTf
(CF3CO)2O (3 eq), CH2Cl2, rt, 2-4 h
Et3SiH (5 eq), TFA (5 eq),
OC10H21-n
OAc
OC10H21-n
Conditions
BnO
O
BnO
H
OBn
OBn OBn
BnO
O
O
OAc
O
AcO
OAc
O
OBn
OBn OBn
BnO
HO
BnO
HO
BnO
AcO
H
H
O
Ph
OAc
O
OAc
O
H
H
O
(83)
H (70)
H
O
OAc
H
H
O
H
(78)
OC10H21-n
OAc
OC10H21-n
(—)
(—)
OAc
O
OAc
O
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
O
H OH OH
482
519
519
494
494
Refs.
569
C57
C56
C44
MPMO
BnO
BnO
MPMO
BnO
BnO
BnO
BnO
OH
O
OBz
OH
O
O
O
OBn
OBn
O
O
O
OBn
OMe
OBn
H
OMe O HO
dr = 1:1
OBz
O
OBn
O
O
H
CH2Cl2, –20°, 20 min
PhMe2SiH (10 eq), TMSOTf,
MeCN, –20°, 20 min
R3SiH (10 eq), BF3•OEt2 (0.1 eq),
Et3SiH, TFA, CH2Cl2, –10°, 72 h
BnO
BnO
+
BnO
BnO
BnO
BnO
O
O
O
OBn
II
OBz
I
O
OBn
O
O
OMe O
OH
OBz
OH
BnO
BnO
OH
O
OBz
O
OBn
O
OBn
OMe
OBn
O
O
OBn
H
3:2
(80)
3:1 (—) PhMe2Si
7:1
I:II (—)
(82) Et3Si
n-Pr3Si
I + II
(86) dr = 1:1
R3Si
O
H
OBn
O
517
517, 774
513
570
C57
BnO OH
O
CH2Cl2, rt, 4 h
The product is a single isomer of undetermined configuration.
O BnO
Et3SiH (12 eq), BF3•OEt2 (2 eq),
The yield was determined by NMR spectroscopy.
BnO
O
OBn
b
O
a
BnO
O
Ph
Conditions
BnO
HO O BnO
OBn O BnO BnO
O
OBn (73)
Product(s) and Yield(s) (%)
TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal
497
Refs.
571
C8
C7
C6
C5
HO
O
N H
AcHN
O 2N
Ph
Ph
N
Et2N
O
N H
N H
O
OH
N H
OH
OH
N H
OH O
OMe
N H
N H
O
O
O
N
Aminal
OH
OH
I (75)
CH2Cl2, 5° to rt, 2 h
Et3SiH (1.2 eq), TFA (3 eq),
O
N H
AcHN
O2N
Ph
Ph
N
Et2N
O
CH2Cl2, 5°, 2 h
Et3SiH (1.2 eq), BF3•OEt2 (1.2 eq),
CHCl3, rt, 1-4 h
Et3SiH (1.5 eq), TFA (10 eq),
CHCl3, rt, 1-4 h
Et3SiH (1.5 eq), TFA (10 eq),
CHCl3, rt, 1-4 h
Et3SiH (1.5 eq), TFA (10 eq),
CHCl3, reflux, 2 h
Et3SiH (1.5 eq), TFA (10 eq),
CHCl3, rt, 1-4 h
Et3SiH (1.5 eq), TFA (10 eq),
CHCl3, rt, 1-4 h
Et3SiH (1.5 eq), TFA (10 eq),
CHCl3, rt, 1-4 h
Et3SiH (1.5 eq), TFA (10 eq),
Conditions
I
NHMe O
NHMe
NHMe
O
NHMe
(94)
(85)
(88)
NHMe
(57)
(84)
NHMe
O
O
O
N Me
(84)
(92)
(86)
Product(s) and Yield(s) (%)
TABLE 21. ORGANOSILANE REDUCTION OF AMINALS AND HEMIAMINALS
521
521
526
526
526
526
526
526
526
Refs.
572
C11
C10
C9-15
C9
Ph
(90) (88)
Bn
N O
Et3SiH, HCO2H, CH2Cl2, rt, 10 h
HCO2
(96)
Ph
OH
(91)
n-C7H15
CHCl3, rt, 1-4 h
(55)
n-C5H11
O
(97)
i-Bu
Ph
(75)
n-Bu
Et3SiH (1.5 eq), TFA (10 eq),
(96)
OH
MeO
n-Pr
H N
CH2Cl2, –15° to rt, 16 h
Et3SiH (10 eq), BF3•OEt2 (3 eq),
CHCl3, rt, 1-4 h
Et3SiH (1.5 eq), TFA (10 eq),
(65)
OH
Et
R
NH
O
N H
Conditions
N
H
O
N Pr-n I
(85)
(91)
O
+
I + II (42), I:II = 3:5
+
NHMe
NHMe
Pr-n (29)
H
O
R
NH
O
O
Product(s) and Yield(s) (%)
TABLE 21. ORGANOSILANE REDUCTION OF AMINALS AND HEMIAMINALS (Continued)
Me
R
HO
Pr-n
MeO
O
Aminal
n-Bu
N
II
O
775
526
527
526
Refs.
573
C16
C13
C12
MeO
BocHN
TBSO
AcHN
N
O
OMe
OMe
OBn
Ac
N
OMe
OTBS
2. Et3SiH, 0°, 30 min
1. TiCl4, CH2Cl2, –78°, 30 min
2. Et3SiH, 0°, 30 min
1. TFA, CH2Cl2, 30 min
Et3SiH, TFA, CH2Cl2, 15 min
CH2Cl2, –40°, 1-2 h
Et3SiH (2 eq), BF3•OEt2 (2 eq),
CH2Cl2, –40°, 1-2 h
Et3SiH (2 eq), BF3•OEt2 (2 eq),
CH2Cl2, 5° to rt, 2 h
Et3SiH (1.2 eq), TFA (3 eq),
CH2Cl2, –40°, 1-2 h
Et3SiH (2 eq), BF3•OEt2 (2 eq),
N
BocHN
TBSO
I (42)
AcHN
H
N
N
O
O
O
(93)
(98)
(97)
(88)
AcHN
OBn
Ac
N
+
I
OTBS
(—)
(—)
OH (51)
524
524
524
521
521
521
521
574
C19-28
C18
C17
C16-17
O
N
R2
O
R1
OTMS
Fmoc N
CF3
Bn
N
MeO2C
AcHN
Rf
OTMS
Ph
Ph
O
O
OH
N
N H
NBn
OMe
Aminal
Et3SiH (3 eq), TFA, CHCl3, rt, 22 h
CH2Cl2, 50°, 24 h
Et3SiH (1 eq), BF3•OEt2 (1 eq),
CHCl3, rt, 20 h
Et3SiH (3 eq), TFA (xs),
CH2Cl2, 5° to rt, 2 h
Et3SiH (1.2 eq), TFA (3 eq),
CH2Cl2, 5°, 2 h
Et3SiH (1.2 eq), BF3•OEt2 (1.2 eq),
CH2Cl2, rt, 5 h
Et3SiH (1 eq), BF3•OEt2 (1 eq),
Conditions
N
R2
Fmoc N
CF3
Bn
N
O
Ph
Ph
N
N H I
O
O
NBn
OH
R1
Me
MeO2C
I (87)
AcHN
Rf
R1 Me Me Me Me i-Pr MeSCH2CH2 Bn BnOCH2 Ph(CH2)4 DNP N N CH2
(61)
(63)
(89)
(84)
(80)
CClF2 CF3CF2
(85)
CF3
Rf
(98) (91) (74) (95) (100) (22) (70) (96) (70) (67)
R2 H c-C6H11 Me Bn H H H H H H
Product(s) and Yield(s) (%)
TABLE 21. ORGANOSILANE REDUCTION OF AMINALS AND HEMIAMINALS (Continued)
528
522
525
521
521
522
Refs.
575
C30
C23
C22
C20 N
O HO
MeO2C
O
O
Cl
NH O OH O
Fmoc N
O
N
Me
MeO2C
MeO
+
O
N H
HO
N
O O
NH O
O
1. TiCl4, CH2Cl2, –78° to 0°
Et3SiH, TFA
Et3SiH (3 eq), TFA, CHCl3, rt, 22 h
O
Et3SiH, TFA
2. Et3SiH
I
NH
H
N
O
O
N
+
O
Cl
N H
O O
II
NH O
(—)
(22) + Cl
O
(15)
MeO2C
I + II (95), I:II = —
O
O
MeO2C
Me OH
Fmoc N
O
N
Me
MeO2C
O
N
(37)
528
776
770
524
576
C12
C11
C10
C8
MeO
Cl
Ph
O
N
H N
N H
N H
CO2Et H N
H N CO2Et
Et3SiH (1.5 eq), TFA, –10°, 0.5 h
Et3SiH (1.5 eq), TFA, –10°, 0.5 h
Et3SiH (1.5 eq), TFA, –10°, 0.5 h
(i-Pr)3SiH (5 eq), TFA, CH2Cl2, rt, 2 h
MeO
Cl
Ph
I (4%)a
H N
CO2Et H N
H N
CO2Et
CO2Et
(92)
(85%)a
(99)
(94)
(80) cis:trans = 42:58
NH2 N I H
N H
(67)
NH2
O
N
Product(s) and Yield(s) (%)
CO2H Et3SiH (5 eq), TFA, CH2Cl2, rt, 2 h
Et3SiH (1.4 eq), TFA, 60°, 48 h
Et3SiH (5 eq), TFA (10 eq), 65°, 25 h
Conditions
TABLE 22. ORGANOSILANE REDUCTION OF ENAMINES
CO2H
CO2Et
Enamine
535
535
535
532
532
533
235
Refs.
577
C14-21
C14
C13
C12
R3
R2
Cl
O
OMe H H OBn
OMe
OMe
H
R
O R
OMe
H
H
4
CO2Et
CO2Et
OMe H
H
H
H
3
NH
R
2
H N
H N
CO2Me
N
OMe
R4
R1
O
1
R
MeO
Br
(95) (80) (80) (33)
5h 20 h
R4 H
R1
O
9h
R3
R2
Cl
O
MeO
Br
MeO
Br
6.5 h
Time
Et3SiH (3 eq), TFA, CH2Cl2, rt
CH2Cl2, 0°, 6 h; rt, 6 h
Et3SiH (1.05 eq), TFA (1 eq),
Et3SiH (1.5 eq), TFA, –10°, 0.5 h
Et3SiD (1.5 eq), TFA-d1, –10°, 0.5 h
Et3SiH (1.5 eq), TFA, –10°, 0.5 h
D H N
H N
O
NH
H
CO2Me
N
D
H N
(56)
CO2Et
CO2Et
CO2Et
(97)
(98)
(99)
538
536
535
535
535
578
C16-19
C16-17
C15
R1
R
1
Cl
N H
R2
N H
R2
R3
R3
i-Pr
N
O
CO2Bu-t
N
Cl
Enamine
Et3SiH (3 eq), TFA, 50°
Et3SiH (1 eq), TFA, 20°
Et3SiH, TFA, CH2Cl2, –42°
Et3SiH, TFA, CH2Cl2, 15 min
Conditions
R1
R1
Cl
N H
R2
N H
R2
R3
R3
i-Pr
N
O
2-CF3C6H4 3-O2NC6H4
CO2Me Ac
CN CO2Me CO2Me CO2Me Ac EtO2C
3-O2NC6H4 Ph 2-O2NC6H4 2-CF3C6H4 3-O2NC6H4 3-O2NC6H4
CO2Me CO2Me CO2Me Ac EtO2C
R3
Ac
CO2Me
CO2Me
CO2Me
CN
R3
CO2Me
R2
2-O2NC6H4
CO2Me
R1
Ph
3-O2NC6H4
R2
(70)
CO2Me
CO2Me
R1
CO2Bu-t
N
Cl
(74) dr = 1:1
Product(s) and Yield(s) (%)
TABLE 22. ORGANOSILANE REDUCTION OF ENAMINES (Continued)
(72)
(60)
(56)
(94)
(55)
(89)
(64)
(69)
(66)
(58)
(63)
529
529
777
524
Refs.
579
C21
C20
C18
C17
BnO
Br
OCO2Et
NHBn
O
O
OH
N
O
O
N
O
N
H N
O
CO2Et
O
Acid TFA TFA-d1 TFA
R1 D H H
Et3SiR (1.5 eq), acid, –10°, 0.5 h
1
Et3SiH, TFA, CHCl3, 20°, 24 h
Et3SiH, TFA, CHCl3, 20°, 24 h
Et3SiH (9 eq), TFA, CHCl3, 20°, 24 h
BnO
Br
H
D
H
R2
R3
O
O
O
H (94)
H (77)
D (63)
R3
OCO2Et
R2
NHBn
N
O
N
O
N
H N
O
CO2Et
(—)
(—)
O (75)
535
537
537
537
580
C27
C22
C21-23
R
2
R1
H N
C11H23-n
N H EtO2C
H N
N H EtO2C
Boc
N
Cl
N H
Ph
Ph
N
Enamine
CO2Et
CO2Et
N
Ph
R3SiH (x eq), TFA, 20°
Et3SiH (2 eq), TFA, rt, 1 h
CH2Cl2, –42°, 4 h
(i-Pr)3SiH (6 eq), TFA (10 eq),
CH2Cl2, –42°, 4 h
Et3SiH (6 eq), TFA (10 eq),
Et3SiH (2 eq), TFA, 50°, 64 h
Conditions
Boc I
N
Cl + N
Cl
H N
N H EtO2C I
+
H N
N H EtO2C
Cl OMe
Cl OMe
C11H23-n
+
H
H
Br F
R2
R1
Ph
Ph
H N N H EtO2C III
CO2Et
+
CO2Et
(81)
Ph
II
CO2Et
N H EtO2C
Ph
Boc III
N
Cl
(80)
(14)
(32)
(25)
H N
Boc II I + II + III (79) I:II:III = 75:10:15
C11H23-n
N H
N
I + II + III (95), I:II:III = 78:9:13
R
2
R1
N
Ph
Product(s) and Yield(s) (%)
TABLE 22. ORGANOSILANE REDUCTION OF ENAMINES (Continued)
CO2Et
530
530
531
C11H23-n
531
534
Refs.
581
C31
a
N H
N
H N
Ph
18 h 1h 18 h 18 h
2 2
Et3Si PhMe2Si 3 3
Et3Si
Et3SiH (2 eq), TFA, 50°, 64 h
N
The yield was determined by NMR spectroscopy.
MeO
MeO
N
O
1.5 h
2
Ph3Si
Time
x
R3Si Et3Si
MeO
MeO
(—)
(—)
(—)
(—)
(—)
N H
—
N
46:44:10
—
—
19:17:64
I + II + III I:II:III
N
O
H N N
(52)
Ph 534
582
C8-20
C8-14
C8-13
C8
Ar
Ph
R
Ph
R1
R1
N
R2
N
N
N
Me Me Me n-Bu n-Bu Ph Ph Ph
H H H H H H H H Me
R2
R2 Me
R1
Me
Imine
55° 55° 50°
PdCl2 (Ph3P)3RhCl
Et3Si Et2HSi PhMeHSi (Ph3P)3RhCl Et2HSi
(C6F5)3B (5-10 mol%), MeC6H5
PhMe2SiH (1.05 eq),
(Ph3P)3RhCl
Et2HSi 55°
(Ph3P)3RhCl 100°
55°
Et3Si
(Ph3P)3RhCl
(Ph3P)3RhCl 100°
Et3Si
0°
(Ph3P)3RhCl
Ph2HSi
30°
Temp
(Ph3P)3RhCl
Catalyst
Et2HSi
R33Si
C6H6, rt, 1 h
R3SiH (1.1 eq), catalyst (0.5 mol%),
Cl3SiH, MeCN, reflux, 4 h
THF, rt, 20 h
PhSiH3 (1 eq), catalyst (10 mol%),
Conditions
72 h
15 h
2h
0.5 h
1.5 h
24 h
20 h
3h
0.5 h
Time
Ar
Ph
R
Bn
R1
(85)
(91)
(96)
(93)
(96)
(90)
(65)
(92)
(95)
N H
R2
NH
R2
SiH2Ph
N H
R1
N
Me (2) +
N
(53)
Ph
(47)
Si
Ph
H
Me
n-Pr
R
Bn
N
Me Bn
Product(s) and Yield(s) (%)
TABLE 23. ORGANOSILANE REDUCTION OF IMINES
(95)
120
546
542
544
Refs.
583
C10
C9
H H H H H Me
Ph
Ph
Ph
Ph
Ph
4-MeOC6H4
Ph
Ph
O
N
Pr-n
N
H
Ph
N
H
Ph
R2
Boc
H
Ph
Ph
R1
t-Bu
H
Ph
rt
Bn
OMe
96 h
23 h
4h
17.5 h
2h
1.5 h
3h
1h
0.5 h
0.5 h
0.5 h
26 h
48 h
Time
C6H6, reflux, 4 h
Cl3SiH (1.2 eq), BF3•OEt2,
C6H6, reflux, 4 h
Cl3SiH (1.2 eq), BF3•OEt2,
THF, rt, 20 h
PhSiH3 (1 eq), catalyst (10 mol%),
rt
rt
Bn
Bn
70°
rt
70°
70°
rt
rt
rt
rt
70°
70°
Temp
Bn
2-MeOC6H4
4-MeOC6H4
Bn
Ph
SO2Ph
allyl
Me
H
Ph
R2
R1
Ar
Ph
O
PhH2Si
(0)
NHPr-n
(89)
R2 Si
R2 N
(89)
H Ph II
N
(82)
(28) (43)
(21) (64)
OMe
n-C5H11
n-Pr H N
n-C5H11
i-Pr
I
R1
(3)
+ R2
R
1
n-C7H15 Me
N I R1
R2
(96)
(95)
(95)
(97)
(86)
(>95)
(91)
(95)
(93)
(60)
(80)
(57)
II
R1
545
545
544
584
C11-14
C11
C10-22
R1
Ph
Ph
S
(97) (88) (86)
Ph Ts Ph 4-MeOC6H4 Bn
2-C4H3O
Ph
Ph
Ph
(86)
(99)
(99)
Ph
R2
2-C4H3S
N H
2-C4H3O
CH2Cl2:DMF (4:1), 0°, 4 h
R1
H N Ph
NHBu-t
I
(77)
(54)
(56)
(22)
Product(s) and Yield(s) (%)
C5H11-n
SiH2Ph
N
NHPh
R2
Cl3SiH (1.5 eq),
Et3SiH (1 eq), TFA (3 eq), 70°, 30 h Ph
I (37)
C6H6, reflux, 4 h
Cl3SiH (1.2 eq), BF3•OEt2,
S I (93)
Ph
Et3SiH (1 eq), TFA, (3 eq), 70°, 6 h
HOAc, KU-1, 55°, 5 h
Et3SiH (1.1-1.2 eq), HCO2H,
THF, rt, 20 h
PhSiH3 (1 eq), 230 (10 mol%),
PhMe2SiH (1.1-1.2 eq), TFA, rt, 16 h
Conditions
TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)
R1
N
Bu-t
N Ph
C5H11-n
R2
N
Ph
N
N
Imine
318
541
545
541
208
544
276
Refs.
585
C12
t-Bu
Ph
N
N
Ph
O
R R = Ph, c-C6H11
Bn
C5H11-n
N
N
PMP N
N
PMP
Cl3SiH, MeCN, reflux, 4 h
PMHS, EtOH, n-butyltris(EH)tin, rt
THF, rt, 20 h
PhSiH3 (1 eq), 230 (10 mol%),
C6H6, reflux, 4 h
Cl3SiH (1.2 eq), BF3•OEt2,
P(OPh)3 (10 mol%), CH2Cl2, 18 h
[Ir(cod)Cl]2 (2.5 mol%),
OC6F5 (2.5 eq), Et2MeSiH, (2.5 eq),
O
P(OPh)3 (10 mol%), CH2Cl2, 18 h
[Ir(cod)Cl]2 (2.5 mol%),
OC6F5 (2.5 eq), Et2MeSiH, (2.5 eq),
O
t-Bu
PhH2Si
O
N
N
PMP
O
Ph
O
N H
N H
N
R
Bn
Bn
C5H11-n
N H
PMP
(48)
(75)
(52) +
Bn
Ph
N
n-C5H11
(81)
Si
H
N
Bn
C5H11-n
(78) trans:cis > 20:1
(60) trans:cis > 20:1
(35)
542
543
544
545
476
476
586
C13
C12-15
N
N
N
Ph
Ph
Ph
C6H11-c
C5H11-n
Bn
Ph
I (40)
Cl3SiH (1.2 eq), BF3•OEt2,
SiH2Ph
Bn
H
Ph Ph C5H11-n
N
(17)
545
545
542
544
541
Si
I (80)
n-C5H11
N
Et3SiH (1 eq), TFA (3 eq), 70°, 1.5 h
(17)
(60)
Ph
543
543
Ph
C6H11-c
(3) +
(84)
543
Refs.
I (82)
N H I
N H
C5H11-n
N
N H
R3
Product(s) and Yield(s) (%)
PMHS, EtOH, rt, n-butyltris(EH)tin
C6H6, reflux, 4 h
Ph
Ph
Cl3SiH (1.2 eq), C6H6, reflux, 4 h
Cl3SiH, MeCN, reflux, 4 h
THF, rt, 20 h
PhSiH3 (1 eq), 230 (10 mol%),
rt, 9 h
n-butyltris(EH)tin (0.1 eq),
PMHS, EtOH, rt,
(81)
N
(76)
6h
n-C6H13 Me Bn
Ph
(82)
H
Ph
(75)
20 h
Time
N H
10 h
H
Ph
Bn
R1
R2
Bn
H
t-Bu
R3
EtOH, rt
n-BuSn[O2CCH(Et)Bu-n]3 (0.1 eq),
PMHS (3 eq),
Conditions
TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)
7h
R2
R3
R1
N
Ph
R1
R2
Imine
587 P(OPh)3 P(OPh)3 P(OPh)3 P(OPh)3 none P(OPh)3 P(OPh)3
[Ir(cod)Cl]2 [Ir(cod)Cl]2
[Ir(cod)Cl]2 none [Ir(cod)Cl]2
Ph 4-O2NC6H4 [Ir(cod)Cl]2 [Ir(cod)Cl]2
1-C10H7
C6F5 C6F5 C6F5 C6F5
dppe (5 mol%), 80°
OPh (2.5 eq), Et2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),
O
Ligand
Catalyst
R
ligand (x mol%), CH2Cl2, 18 h
OR (2.5 eq), Et2MeSiH, (1 eq) 230 (2.5 mol%),
O
THF, rt, 20 h
PhSiH3 (1 eq), 230 (10 mol%),
Et2O, rt, 10 h
PMHS (5 eq), ZnCl2 (2 eq),
Et2O, rt, 10 h
PMHS (5 eq), ZnCl2 (2 eq),
HOAc, KU-1, 55°, 5 h
Et3SiH (1.1-1.2 eq), HCO2H,
I
Ph
Ph
rt
rt
rt
rt
rt
rt
50°
Temp
N
(15) + Ph
(58)
(0)
(28)
(68)
(56)
(13)
(14)
(20) dr > 20:1
Ph N SiPhH2
I (20) dr > 20:1
5
10
—
10
10
10
10
x
O
Ph
I (67)
I (67)
I (71)
N Ph
Ph Si N Ph
H Ph
(47)
476
476
544
539
539
208
588
C13-15
C13-14
C13
R2
Ph
R1
H H Et Me H H
Ph
3-O2NC6H4
n-C5H11
Ph
4-MeC6H4
4-MeOC6H4
R2
N
Ph
H
—(CH2)5—
NTs
N
R2
N
c-C6H11
R1
R1
O 2N
Ph
Ph
Imine
OC6F5 (2.5 eq),
Conditions
50 h
59 h
59 h
50 h
56 h
42 h
67 h
48 h
Time
LiOMe (4 mol%), THF, rt, 0.5 h
(MeO)3SiH (1.2 eq),
60-70°, 30-60 min
Et3SiH (1 eq), TFA (3 eq),
Et2O, rt, 12 h
PMHS (5 eq), ZnCl2 (2 eq),
P(OPh)3 (10 mol%), CH2Cl2, 18 h
[Ir(cod)Cl]2 (2.5 mol%),
Et2MeSiH, (2.5 eq),
O
R2
R1
Ph
Ph
NHTs
N
(80)
(97)
(63)
(80)
(92)
(100)
(84)
(62)
R1
O2N
O
R2
NHBn
N H
Ph
Me (95) H
(86)
(78)
H
H
R2
Me
H
R1
(75)
(68) trans:cis = —
Product(s) and Yield(s) (%)
TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)
294
540
539
476
Refs.
589
C14
C13-16
S
OMe
n-C5H11
N
Bn
N
Ph
reflux, 4 h
Cl2SiH2 (1.2 eq), C6H6,
C6H6, reflux, 4 h
Cl3SiH (1.2 eq), BF3•OEt2,
P(OPh)3 (10 mol%), CH2Cl2, 18 h
[Ir(cod)Cl]2 (2.5 mol%),
OC6F5 (2.5 eq), Et2MeSiH (2.5 eq),
O
Et2O, rt, 10 h
PMHS (5 eq), ZnCl2 (2 eq),
EtOH, rt,
PMHS, n-butyltris(EH)tin,
S
I (90)
O
I (73)
Ph
N H
I
H N
Ph
Bn
Ph
Ar
OMe
N
N H I
(73)
N
(76)
4-(i-Pr)C6H4
Ph
(88)
3-MeOC6H4
Et2O, rt, 15 h
(78)
2-MeOC6H4
Ph
(62)
4-MeOC6H4
N
(69)
H N
2-ClC6H4
Ph
Ph (79)
PMHS (5 eq), ZnCl2 (2 eq),
Cl3SiH, MeCN, reflux, 4 h
4-ClC6H4
Ar
Ph
Ar
N
Ph
Ph
C5H11-n
(61)
(50) trans:cis > 20:1
(76)
(60)
545
545
476
539
543
539
542
590
C17
C16
C15
Ph
N
CO2Me
NHTs
N
N
Ph
n-C6H13
N
Ph
Ph
Bn
Ph
Ph
Imine
20° 20° 20° 40°
AlCl3 TiCl4 BF3•OEt2 ZnCl2
P(OPh)3 (10 mol%), CH2Cl2, 18 h
[Ir(cod)Cl]2 (2.5 mol%),
OC6F5 (2.5 eq), Et2MeSiH (2.5 eq),
O
Temp
Catalyst
Ph2SiH2 (1.2 eq), catalyst (1 eq), CH2Cl2
EtOH, rt
PMHS, n-butyltris(EH)tin,
Et2O, rt, 20 h
PMHS (5 eq), ZnCl2 (2 eq),
P(OPh)3 (10 mol%), CH2Cl2, 18 h
[Ir(cod)Cl]2 (2.5 mol%),
OC6F5 (2.5 eq), Et2MeSiH (2.5 eq),
O
Conditions
N
O
Ph
Ph
N H
N
Ph
(48)
(63)
(90)
(90)
(55)
(70) trans:cis = 5.2:1
(80) trans:cis > 20:1
Bn (81)
Ph
Ph
N H
CO2Me
NHTs
n-C6H13
Ph
O
Product(s) and Yield(s) (%)
TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)
476
373
543
539
476
Refs.
591
C19
C18
Ph
Ph
Ph
O
Ph
N
N
N
Bn
O
Bn
•
C5H11-n
N
N
Ph
Ph
Et3SiH, Cl3CCO2H
THF, rt, 20 h
PhSiH3 (1 eq), 230 (10 mol%),
Et2O, rt, 12 h
PMHS (5 eq), ZnCl2 (2 eq),
Et2O, rt, 24 h
PMHS (5 eq), ZnCl2 (2 eq),
EtOH, rt, 10 h
n-butyltris(EH)tin (0.1 eq),
PMHS (3 eq),
Ph
Ph
Ph
O
Ph
N H
Bn
SiH2Ph
N H
O
Bn
•
C5H11-n
N
H N
N H
(0)
Ph
N
Ph H
n-C5H11
(50)
(63)
(0) +
Ph
Ph
(82)
Si
Ph C5H11-n
N
Ph Ph (0)
778
544
539
539
543
592
C23-26
R1
Ph 3-O2NC6H4 PhCH(OH)CHMe PhCH(OH)CHMe
Cl(CH2)4
Cl(CH2)4
Cl(CH2)4
allyl
R2
N
N
R1
R2
N
O
R1
R2
N
N
O
Imine
CH2Cl2, rt, 16 h
Et2SiH2 (2.2 eq), (Ph3P)3RhCl,
Conditions
N
R2
HN
R1
O
(69)
(78)
(82)
(81)
N
O R1
R2
NH
N
Product(s) and Yield(s) (%)
TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)
547
Refs.
593
C9
C8
C7
C5
Ph
N
O
Ph
O
N OH
OH
N
O
N
OH
N
OH
OH
OH
Ph
MeO
Ph
N
O
N
OH
Hydroxylimine
10% Pd-C, 40-50°, 3 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
10% Pd-C, 40-50°, 4 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
10% Pd-C, 40-50°, 6 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
10% Pd-C, 40-50°, 5 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
10% Pd-C, 40-50°, 4 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
10% Pd-C, 40-50°, 3 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
10% Pd-C, 40-50°, 3 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
Conditions
Ph
O
I
O
H N
O
Boc
N H
(82)
(90)
(85)
Boc
Boc (65)
HN Boc
Boc
Boc
H N
I (75)
Ph
MeO
Ph
H N
O
H N
(80)
(85)
Product(s) and Yield(s) (%)
TABLE 24. ORGANOSILANE REDUCTION OF HYDROXYLIMINES
548
548
548
548
548
548
548
Refs.
594
C10
C9-15
MeO
MeO
OMe
N
OMe
OMe NOAc
OMe
OH
NOAc
0°
7
Me
t-Bu
2h
0°
1
Bn
10% Pd-C, 40-50°, 5 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
CH2Cl2, rt, 9 h
Et3SiH (1.2 eq), TMSOTf (0.1 eq),
CH2Cl2, 0°, 2 h
Et3SiH (1.2 eq), TMSOTf (0.1 eq),
Et3SiH, TFA
2h
rt
3
Me
OBz
6h 10 h
0°
1
N
Time
Temp
n
CH2Cl2
Et3SiH (1.2 eq), TMSOTf (0.1 eq),
Me
n
NOAc
Conditions
n
MeO
MeO
OMe
t-Bu
(78)
(66)
(80)
(65)
OR
I
OMe
H N
OMe
CN
CN
+ t-Bu
OMe
Boc
CN
(81)
(82)
(82)
I + II (85), I:II = 5:1
H
NHOBz
II
Product(s) and Yield(s) (%)
TABLE 24. ORGANOSILANE REDUCTION OF HYDROXYLIMINES (Continued)
R
OR
Hydroxylimine
H NHOBz
548
552
552
550
552
Refs.
595
C12-13
C12
Me
N
R
n
O
OBz
Me
n-C7H15
O
OH
Me
Ph
N
H
Ph
—(CH2)5—
R2
Ph
N
OR3
R1
R1
AcON
R2
C10-16
Bn
Bz
Bn
Bn
Ac
R3 rt rt rt rt 50°
1.2 1.2 1.2 2
Time
5d
overnight
overnight
24 h
overnight
CH2Cl2
Et3SiH (1.2 eq), TMSOTf (0.1 eq),
Et3SiH, TFA
10% Pd-C, 40-50°, 7 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
Temp
x 1.2
TFA or TFA-CH2Cl2 (1:1)
PhMe2SiH (x eq),
O
R
R2
O
n
NHOBz
(23)
(78)
(75)
(65)
H N
NHOR3
(67)
R1
CN
Boc
Et
Me
0°
rt
4h
6h
Temp Time
(95)
2
R
(85)
1
n
(80)
(81)
(61)
552
550
548
276, 551
596
C13-20
C13
C12-23
R
R2
OBz
Me Me
Ph
PhCH2
P
EtO
N
Ph
OH
OEt
O
t-Bu
Ph
(62) (79) (73) (79) (65) (54)
i-Bu Ph Bn BnCH2
OEt
O
i-Pr
EtO
P
(66)
R
(75)
NHOBn
Ph
Boc
Et
Et3SiH (2 eq), TFA (as solvent), 40°, 12 h
10% Pd-C, 40-50°, 7 h
HN
(85) cis:trans = 5:1
(82)
(90)
(0)
(54)
Product(s) and Yield(s) (%)
Me
R
—(CH2)11—
H
4-MeC6H4
(95)
R2
NHOBz
(85)
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
R
1
—(CH2)5—
R2
Et3SiH, TFA, 0.5-6 h
Conditions
TABLE 24. ORGANOSILANE REDUCTION OF HYDROXYLIMINES (Continued)
—(CH2)4—
R1
N
BnO
Ph
R1
N
Hydroxylimine
553
548
550
Refs.
597
C17
C16
C15
N
O
t-Bu
MeO
OBn
MeO
O
N
Cl
N
Ph N
Cl N
NOAc
H
OBz
OH
OBn
OMe
OH
O
OBz
OH
Et3SiH (2 eq), TFA
10% Pd-C, 40-50°, 6 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
CH2Cl2, rt, 3 h
Et3SiH (1.2 eq), TMSOTf (0.1 eq),
10% Pd-C, 40-50°, 3 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
Et3SiH (2 eq), TFA
10% Pd-C, 40-50°, 6 h
PMHS (3 eq), (t-BuCO)2O (1.1 eq),
t-Bu
MeO
N H
I
+
t-Bu I + II (85), I:II = 5:1
NHOBz
Cl
(80)
(90)
(54)
Boc
(90)
(80)
CN
H
Boc
OBn
OMe
Cl
Ph
NHOBz
O
Boc
O
HN
H N
O
OBn
MeO
II
NHOBz
550
548
552
548
550
548
598
C44
C35-42
C19
C18
R4
MsO
OBz H
R2
N
R
7
H
Me
R8
PhMe2SiH (2.3 eq), TFA, 60°, 40 min
CH2OBz H
OBz CH2OBz H
OBz OBz
OBz H
R
6
PhMe2SiH (2.3 eq), TFA
Et3SiH (2 eq), TFA
PhMe2SiH (1.2 eq), TFA, rt
PhMe2SiH (1.2 eq), TFA, rt
Conditions
R4
BzO
I
OH
+
+
NHOBn
R2
N OBz R1
(85) (90)
(88)
(82)
R2
OMs R1
R8
12
I NHOCOPh
OAc
NHOBn
R3
BzO
R
6
R5
R7
Ph
Ph
OAc
NHOBn
II
(73)
I + II (77), I:II = 25:75
OAc
(73)
OBz (70)
R2
I + II (73), I:II = 99:1
OAc
NHOBn
II
OBz H
H
R1
Ph
Ph
NHOBn
Product(s) and Yield(s) (%)
TABLE 24. ORGANOSILANE REDUCTION OF HYDROXYLIMINES (Continued)
OBz H
H
H
OTBDPS
OBz OBz H
OBz OBz R1
H
OBz H
OBz OBz H
R
5
OBz H
R
4
H
R
3
OBz H
R2
OBn
H
R
1
R2
N
OCOPh
OMs R1
R8
12
N
OAc
OAc
OBn
N
N
R3
BzO
R
6
R5
R7
Ph
Ph
BnO
Hydroxylimine
549
549
550
551
551
Refs.
599
C6-9
C6
R
ACHN (0.2 eq), MeC6H5, 110°, 5 h
(85) (75)
2h 3h 3h 6h 2h 2h 2h 3h 3h 2h 2h 2h
2,4-Me2
2,6-Me2
3,5-Me2
2,4,6-Me3
4-MeO
4-Cl
4-Br
4-CHO
4-Ac
3-Ac
4-MeO2C
4-CN
(0)
(49)
(71)
(—)
(—)
(—)
(71)
(86)
(83)
(83)
(82)
4h
3,4-Me2
(90)
(86)
2h
2h
R
4-Me
Time
MeC6H5
Et3SiH (5 eq), (Ph3P)3RhCl (0.02 eq),
PMHS, Pd/C, EtOH, 80°
2. ACHN (0.3 eq), MeC6H5, 110°, 3 h
H
NO2
NO2
CN
1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),
Conditions
NH2
NH2
CN
(89)
(67)
Product(s) and Yield(s) (%)
TABLE 25. ORGANOSILANE REDUCTION OF NITROALKANES
R
NO2
Nitro Compound
554
316
555
Refs.
600
C12
C10
C8
C7
O
CO2Et
NO2
NO2
NO2
NO2
NO2
TBSO
EtO2C
CO2Et
Nitro Compound
(78)
360 h 240 h 120 h
MeC6H5 MeC6H5 MeC6H5 MeC6H5, EtOAc 240 h
0.01 0.02 0.05 0.02
8.0 5.0 5.0 5.0
2. ACHN (0.3 eq), MeC6H5, 110°, 3 h
ACHN (0.2 eq), MeC6H5, 110°, 5 h
1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),
2. ACHN (0.3 eq), MeC6H5, 110°, 3 h
ACHN (0.2 eq), MeC6H5, 110°, 5 h
1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),
(89)
360 h
MeC6H5
0.01
8.0
O
TBSO
(82)
(—)
(76)
(—)
360 h
(73)
360 h
MeC6H5
0.01
5.0
Time
C6H6
Solvent
0.01
y
EtO2C
5.0
x
Et3SiH (x eq), (Ph3P)3RhCl (y eq)
2. ACHN (0.3 eq), MeC6H5, 110°, 3 h
ACHN (0.2 eq), MeC6H5, 110°, 5 h
1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),
2. AIBN (0.3 eq), MeC6H5, 110°, 3 h
AIBN (0.2 eq), MeC6H5, 110°, 5 h
1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),
Conditions
NH2
CO2Et
CO2Et
(76)
(78)
(67)
(76)
Product(s) and Yield(s) (%)
TABLE 25. ORGANOSILANE REDUCTION OF NITROALKANES (Continued)
555
555
554
555
555
Refs.
601
C18
C16
C13
BnO
O2N
MsO
MsO
NO2
O
OBn
O
NO2
O
OMs
2. ACHN (0.3 eq), MeC6H5, 110°, 3 h
ACHN (0.2 eq), MeC6H5, 110°, 5 h
1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),
MeC6H5, reflux, 4 h
Et3SiH (5 eq), (Ph3P)3RhCl (2 mol%),
2. ACHN (0.3 eq), MeC6H5, 110°, 3 h
ACHN (0.2 eq), MeC6H5, 110°, 5 h
1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),
BnO
H2N
MsO
MsO
O
OBn
O
(71)
O
OMs
(—)
(70)
555
554
555
602
C6
C5-10
c-C6H11 Ph Bn 3-MeC6H4 Ph
H
H
H
H
Me
Cl
O 2N
Cl
n-C5H11
H
N3
N2+ BF4—
N2+ BF4—
Cl
N3
i-Pr
H
OH
R2 Me
R1
R2
Me
N H
N
R1
O
Et3SiH, MeCN, rt, 16 h
Et3SiH, MeCN, rt, 16 h
(Boc)2O (1.1 eq), EtOH, rt, 3 h
PMHS (3 eq), 10% Pd-C,
(Boc)2O (1.1 eq), EtOH, rt, 5 h
PMHS (3 eq), 10% Pd-C,
Et3SiH (2 eq), TFA, 0°, 4 h
Conditions
Cl
O N H R1
R2
Cl
NO2
Cl
(70)
(72)
(88)
(90)
NHBoc
NHBoc
OH
(56)
(84)
(85)
(89)
(94)
(74)
(95)
(86)
H N
Product(s) and Yield(s) (%)
TABLE 26. ORGANOSILANE REDUCTION OF MISCELLANEOUS NITROGEN COMPOUNDS Nitrogen Compound
563
563
557
557
561
Refs.
603
C7
C7-8
C6-13
O
+
n
MeO
N3
N3
reflux, 90-120 min
n-PrOH (2 eq), C6H6, AIBN (5 mol%),
PMHS (1.5-2 eq), [(n-Bu)3Sn]2O (0.025 eq),
reflux, 90-120 min
n-PrOH (2 eq), C6H6, AIBN (5 mol%),
O
HO2C
I (91)
MeO
PhSiH3 (1.5-2 eq), [(n-Bu)3Sn]2O (0.025 eq),
(Boc)2O (1.1 eq), EtOH, rt, 3 h
PMHS (3 eq), 10% Pd-C,
(Boc)2O (1.1 eq), EtOH, rt, 4 h
PMHS (3 eq), 10% Pd-C, Ph
(83)
N3
(84)
1-Ad
n
(41)
1-C10H7
2. Et3SiH
(90)
Bn
O
(61)
Ph
O
(71)
t-Bu
1. NOBF4, SO2
(85)
n-Bu
RCHO (79)
N3
Et3SiH (2 eq), CH2Cl2, rt, 0.5-6 h
i-Pr
NEt BF4–
c-C3H5
R
HO2C
Ph
R
I
NHBoc
NH2
(51)
(40)
(94)
(90)
(94)
NHBoc
2
1
n
556
556
557
557
779
28, 562
604
C7
C7-14
C7-9
MeO
R
R
+
N2+ BF4–
N2+ BF4–
NPr-i FeCl4–
CN
Et3SiH, MeCN, rt, 16 h
Et3SiH, MeCN, rt, 16 h
rt, 0.5-6 h
Et3SiH (1.5 eq), CH2Cl2,
CO, –20°
TMSH (10 eq), Co2(CO)8 (0.08-0.25 eq),
Conditions
RCHO
R
OMe
(11) (88) (53) (36) (73) (46)
4-MeO 4-Cl 4-NCCH2 4-Me2N 4-MeO2C
(42) (91)
2-EtO2CC6H4 1-Ad
(90)
(25)
(0) (56) PhCH=CH
(78)a 4-OHCC6H4 4-AcC6H4
(57)
(88)
4-MeC6H4
(19)a
(97)
4-O2NC6H4
4-NCC6H4
(53)
4-ClC6H4
4-MeOC6H4
(87)
Ph
(77)
(57)
2-Me
(91)
4-Me 3-Me
(61)
H
c-C3H5
R
TMS
TMS
N
R
Product(s) and Yield(s) (%)
TABLE 26. ORGANOSILANE REDUCTION OF MISCELLANEOUS NITROGEN COMPOUNDS (Continued) Nitrogen Compound
563
563
28
559
Refs.
605
C9-11
C9
C8
R
R
+
NEt BF4–
N3
Ph
H N
N3
N3
Ph
Ph
OH
CO2—
N2+
CO2H
N2+ Cl–
Et3SiH (1.2 eq), CH2Cl2, rt, 0.5-6 h
THF, rt, 3-5 h
PMHS (2 eq), (Ph3P)4Pd (0.01 eq),
(Boc)2O (1.1 eq), EtOH, rt, 4 h
PMHS (3 eq), 10% Pd-C,
(Boc)2O (1.1 eq), EtOH, rt, 4 h
PMHS (3 eq), 10% Pd-C,
(Boc)2O (1.1 eq), EtOH, rt, 4 h
PMHS (3 eq), 10% Pd-C,
Et3SiH, CH2Cl2, reflux, 2 h
Et3SiH, THF, reflux, 2 h
RCHO
RNH2
I (89)
Ph
Ph
OH
+
I
NHBoc
(0) (60) (0) (54)
4-NCC6H4 4-AcC6H4 PhCH=CH
(85) 4-MeOC6H4 4-OHCC6H4
(92)
4-MeC6H4
(88)
4-EtOC6H4
(21)
(92)
Bn
(61)
(90)
4-O2NC6H4
(89) Ph
(9)
CO2SiEt3
c-C6H11
R
(90)
(88)
4-ClC6H4
R
(78)
(29) +
NHBoc
SiEt3
CO2H
28
270
557
557
557
563
563
606
C11
C10-15
C10
Ph
(92) (82) (78) (79) (46)
Ph Bn 3-MeC6H4 Ph
H
H
H
Me
CO, –20°
(80)
c-C6H11
H
CN
(91)
n-C5H11
H
(86)
H N
i-Pr
N H
Me
Ph
O
NH Ts
H
TMSH (10 eq), Co2(CO)8 (0.08 eq),
Et3SiH (2 eq), TFA, 0°, 4 h
H N
R2
R1
R2
Et3SiH (2 eq), TFA, 0°, 1 h
I (96)
I
NH2
Me
N H
N
NH Ts
2. AIBN (5 mol%), reflux, 90-120 min
n-PrOH (2 eq), C6H6
[(n-Bu)3Sn]2O (0.025 eq),
1. PMHS (1.5-2 eq),
2. AIBN (5 mol%), reflux, 90-120 min
n-PrOH (2 eq), C6H6
[(n-Bu)3Sn]2O (0.025 eq),
1. PhSiH3 (1.5-2 eq),
R1
O
N
N3
Conditions
R1
TMS
(80)
TMS
N
R2
(99)
(64)
Product(s) and Yield(s) (%)
TABLE 26. ORGANOSILANE REDUCTION OF MISCELLANEOUS NITROGEN COMPOUNDS (Continued) Nitrogen Compound
559
561
560
556
556
Refs.
607
C12 NH Ts NH Ts
N
n-C8H17
NH Ts
N
n-C10H21
i-Pr
Et
N
N3
N3
2. AIBN (5 mol%), reflux, 90-120 min
n-PrOH (2 eq), C6H6
[(n-Bu)3Sn]2O (0.025 eq),
1. PMHS (1.5-2 eq),
2. AIBN (5 mol%), reflux, 90-120 min
n-PrOH (2 eq), C6H6
[(n-Bu)3Sn]2O (0.025 eq),
1. PhSiH3 (1.5-2 eq),
2. AIBN (5 mol%), reflux, 90-120 min
n-PrOH (2 eq), C6H6
[(n-Bu)3Sn]2O (0.025 eq),
1. PMHS (1.5-2 eq),
2. AIBN (5 mol%), reflux, 90-120 min
n-PrOH (2 eq), C6H6
[(n-Bu)3Sn]2O (0.025 eq),
1. PhSiH3 (1.5-2 eq),
Et3SiH (2 eq), TFA , 0°, 1 h
Et3SiH (2 eq), TFA, 0°, 1 h
Et3SiH (2 eq), TFA, 0°, 1 h
I (94)
n-C8H17
I (95)
H N
H N
n-C10H21
i-Pr
Et
H N
I
I
NH Ts
NH Ts
NH Ts
NH2
NH2
(89)
(30)
(79)
(92)
(94)
556
556
556
556
560
560
560
608
C15
C14
C12
PMP
Ph
Ph
EtO2C
N3
N NH Ts
N NH Ts
N NH Ts
N NH Ts
N NH Ts
OEt
N NH Ts
n-C6H13
Ph
Et3SiH (2 eq), TFA, 0°, 1 h
Et3SiH (2 eq), TFA, 0°, 1 h
Et3SiH (2 eq), TFA, 0°, 1 h
Et3SiH (2 eq), TFA, 0°, 1 h
Et3SiH (2 eq), TFA, 0°, 1 h
Et3SiH (2 eq), TFA, 0°, 1 h
n-PrOH, AIBN, 80°
PhSiH3, (n-Bu)3SnH (cat.),
Conditions
PMP
Ph
Ph
EtO2C
H N NH Ts
H N NH Ts
(81)
(51)
(82)
560
560
560
560
560
(82)
(84)
560
556
Refs.
(75)
(—)
H N NH Ts
H N NH Ts
H N NH Ts
NH
OEt
H N NH Ts
n-C6H13
Ph
Product(s) and Yield(s) (%)
TABLE 26. ORGANOSILANE REDUCTION OF MISCELLANEOUS NITROGEN COMPOUNDS (Continued) Nitrogen Compound
609
C19
C16
I
a
N3
Cl
N3
N H
O N
Bn
Cl
O
N NH Ts
CO2Et
Cl
Et3SiH, TFA, 0° to rt, 24 h
NH-Gly-Gly-OEt Et3SiH, 20% Pd(OH)2/C, (Boc)2O
(Boc)2O (1.1 eq), EtOH, rt, 5 h
PMHS (3 eq), 10% Pd-C,
Et3SiH (2 eq), TFA, 0°, 1 h
The yield was determined by gas chromatography.
NC
I
BocHN
NC
Cl
N H
O
NH
CO2Et
Cl
NHBoc
H N NH Ts
Bn
O
Cl
(97)
NH-Gly-Gly-OEt
(85)
(76)
(80)
780
558
557
560
610
C16-20
C11-12
C10
C8-14
C6
R
R
S
S
S
+
S
SAr
SMe
SH
R
S 2
2 BF4–
Sulfur Compound
(0) (74)
2,4-(O2N)2C6H3 4-MeOC6H4
R
CH2Cl2, 0°, 20 h
Et3SiH (3-5 eq), BF3•OEt2,
20 h 22 h
1-Np 2-Np
168 h
20 h Bn
Time
(70)
Ph
92 h
24 h
Ar
SMe
+ ArSH
(0)
2-O2NC6H4
(20)
(52)
Ph
Time
(45)
Ph
(13) +
(67)
n-Bu
R
(100)
CH2Cl2, 0°
I
I
S
H
R
RSH
S
S
(25)
(50)
(40)
(30)
% Conv.
(5.5)
Product(s) and Yield(s) (%)
Et3SiH (3-5 eq), BF3•OEt2,
CH2Cl2, rt, 6 h
Et3SiH (1.3 eq), BF3•OH2 (4-6 eq),
Et3SiH (1.4 eq), TFA, 60°, 25 h
Et3SiH (1 eq), MeCN, 9:1
(66)
— 1:1
(54)
1:3 (71)
(51)
cis:trans
CO2Me
(48)
R
3
R5
R4
(69)
(76)
Me
R2
O
I (62)
Br
Br
—(CH2)3—
H
Me
H
R5
CH2Cl2, –78°, 45 min; rt, 3 h
2. Et3SiH (1.1 eq), BF3•OEt2 (1.1 eq),
1. LDA/THF; R4R5CO; TBAF a
I
I
I (76)
Ph
Ph
I
OH
I (69)
Ph
Me
Me
Me
H
Me
Me
R4
H
R3
R2
R2
R1
R1
R3
CO2Me
CH2Cl2, rt, 10 min
HMe2SiOSiMe2H (1.0 eq), I2 (1.6 eq),
NaI (1.3 eq), CH2Cl2, 5-10°, 45 min
HMe2SiOSiMe2H (1.0 eq),
TMSCl (1.5 eq), MeCN, reflux, 45 min
PMHS (1 eq), NaI (1.33 eq),
LiBr (1.3 eq), TFA, 5-10°, 1.5 h
HMe2SiOSiMe2H (1.0 eq),
LiBr (1.3 eq), TFA, 5-10°, 15 h
HMe2SiOSiMe2H (1.0 eq),
TMSCl (1.5 eq), HOAc, reflux, 15 min
PMHS (1 eq), LiBr (1.33 eq),
(69)
765
357
357
567
357
357
567
614
C17
C16
C15
C14
C11
C10
Ph
Ph
Ph
Ph
N
Ts
N
Ts
O
EtO2C
O
Ph
CO2Me
N
Ts
N
Ts
Small Ring Substrate
PMHS (xs), EtOH, Pd-C, rt, 6 h
PMHS (xs), EtOH, Pd-C, rt, 6 h
PMHS (xs), EtOH, Pd-C, rt, 6 h
Et3SiH (3.9 eq), BF3, CH2Cl2, 20°, 7 d
PMHS (xs), EtOH, Pd-C, rt, 6 h
TMSCl (1.5 eq), MeCN, reflux, 7 h
PMHS (1 eq), NaI (1.33 mol%),
NaI (1.3 eq), CH2Cl2, 5-10°, 20 min
HMe2SiOSiMe2H (1.0 eq),
Conditions
Ph
Ph
Ph
Ph
EtO2C
I (46)
Pr-i I
I
NHTs
(80)
I
I II
(34)
(95)
(60)
(96)
(100)
NHTs
NHTs
Ph
i-Pr
NHTs
CO2Me
+
+ I + II (80), I:II 57:43
Product(s) and Yield(s) (%)
TABLE 28. ORGANOSILANE REDUCTION OF SMALL RING COMPOUNDS (Continued)
568
568
568
566
568
567
357, 567
Refs.
615
C24
C23
C21
C20
C19
a
Ar
Ph
Ph
Ph
Ph
Ts N
N
Ts
N
Ts
Ph
N
Ts
O
OBn
CO2Et
Ar = 3-PhOC6H4
CO2Et
Ph
Ph
N
Ts
CO2Et
CO2Et
PMHS (xs), EtOH, Pd-C, rt, 6 h
PMHS (xs), EtOH, Pd-C, rt, 6 h
CH2Cl2, 20°, 30 h
Et3SiR (1.1 eq), TFA (2.6 eq),
PMHS (xs), EtOH, Pd-C, rt, 6 h
PMHS (xs), EtOH, Pd-C, rt, 6 h
PMHS (xs), EtOH, Pd-C, rt, 6 h
PMHS (xs), EtOH, Pd-C, rt, 6 h
Ar
Ph
Ph
Ph
Ph
PMP
O
O
R
NHTs
(93)
(90)
(75)
D
H
R
(97)
CO2Et
OBn
Ph
CO2Et
NHTs
Ph
Ph
NHTs
NHTs
CO2Et
NHTs
CO2Et
NHTs
(—)
(93)
(85)
(80)
These sequential steps generate the intermediate substituted tetrahydrofuran-2-ol, which is converted in the second sequence into the final product shown.
PMP
O
Ts N
568
568
781
568
568
568
568
616
C20
C19
C18-20
R2 Et Et Me
R1 n-Pr i-Pr Ph (90)
(95)
(95)
R1
CO2R2
(i-Pr)3SiH, MeC6H5
H
Ph3C+ –Br5-CB9H5
Me
, C6H6, reflux, 4 h
Ph3CH +
Ph3CH +
Ph3CH (—)
Me
1-Np Si
Ph Cl
(71)
[(i-Pr)3Si][Br5-CB9H5] (—)
[(i-Pr)3Si-NCMe][Br5-CB9H5] (—)
+
46
46
60
62
Ph3CH (100) + Et2SiHF (100)
Et2SiH2 (0.80 eq), rt, 1.5 h Ph
62
Ph3CH (100) + Me2SiF2 (95)
Me2SiH2 (0.45 eq), rt, 8 h
Si
62
Ph3CH (100) + Me2SiHF (100)
Me2SiH2 (0.8 eq) rt, 0.5 h
1-Np
62
62
782
Refs.
Ph3CH (100) + Et3SiF (100)
Ph3CH (100) + Me3SiF (100)
MeS
N
Product(s) and Yield(s) (%)
Et3SiH (0.8 eq), rt, 1.5 h
TMSH (0.8 eq), rt, 0.5 h
Et3SiH, TFA, MeCN
(i-Pr)3SiH, MeCN
R1
Conditions
TABLE 29. MISCELLANEOUS ORGANOSILANE REDUCTIONS
Ph3C+ –Br5-CB9H5
Ph3CCl
Ph3C+ BF4–
TBSO
SMe NHCO2R2
Substrate
617
C43
Ph3C+ (C6F5)4B–
C6D6 C6D6 MeC6H5 MeCN C6D6 C6D6
Et3Si Et3Si Et3Si (i-Pr)3Si (TMS)3Si
Solvent
TMS
R3Si
R3SiH
Ph3CH (—)
+
R3Si+ B(C6F5)4 – (—) 45
618
C4-8
C4
O
O
R
O
Ketone
n-BuLi (1.14 mol%), THF, rt
Me(EtO)2SiH (3.75 eq), 197 (0.57 mol%),
MeLi (1.14 mol%), THF, rt
[—(Me)(H)SiO—]4 (1.43 eq), 197 (0.57 mol%),
MeLi (1.14 mol%), THF, rt
Me(EtO)2SiH (1.43 eq), 197 (0.57 mol%),
23 (1.1 mol%), 0°, DME, 26 h
Ph2SiH2 (4 eq), [Rh(cod)2]BF4 (1.0 mol%),
Conditions
R
OH
R
OH
R
OH
I
OH
OH
(100)
(100)
+
Conf.
Time
R
S R S R Conf.
5 38 45 41 % ee
12 h 72 h 12 h 12 h
n-Pr t-Bu s-Bu Ph
R S R S R
2 21 42 39 99
(100) (100) (75) (100) (100)
12 h 140 h 140 h 24 h
i-Pr t-Bu s-Bu Ph
Time
S
19 12 h i-Pr
1h Et
R
R % ee
12 h
Ph
R
S 47
12 h
s-Bu
7
R 50
72 h
t-Bu
1h
S
6 48
12 h
n-Pr
Et
S
R
Conf.
17
7
% ee
12 h
1h
Time
I = 96% ee
I + II (94), I:II 90:10,
i-Pr
Et
R
II
OH
OH
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES
583
583
583
577
Refs.
619
C4-10
R1
O
R2
>99
(100)
Ph
12 h
(EtO)3SiH
R1
44
(80)
Ph
120 h
MeSiH3
2. PhMgBr
R2
n-Bu n-Pr Et s-Bu t-Bu n-Pr Et2NCH2 Ph n-C5H9 n-Bu c-C6H11
MeOCH2 550 h BnCH2 c-C6H11
Me Et i-Pr Me Me i-Pr Me Me Et i-Pr Et Ph Me i-Pr
1270 h
25 h
18 h
1200 h
600 h
300 h
300 h
680 h
230 h
230 h
230 h
230 h
18 h
150 h
Me
i-Pr
18 h
18 h
Time
n-Pr
Et
R
R
R
S
S
R
Conf.
Me
Me
R2
53
(100)
Ph
24 h
PMHS
R1
17
i-Pr (100)
12 h
(EtO)3SiH
OH
15
i-Pr (100)
12 h
PMHS
1. R3SiH (1 eq), catalysta (0.1 eq), rt
2
Et
1h
% ee (100)
R
Time
PMHS
R
OH
R3SiH
n-BuLi (1.14 mol%), THF, rt
R3SiH (3.75 eq), 197 (0.57 mol%),
(68)
(96)
(84)
(92)
(75)
(94)
(90)
(91)
(63)
(87)
(99)
(91)
(97)
(92)
(96)
(93)
(89)
(5)
11
15
8
37
70
90
4
60
40
27
65
11
5
18
19
10
% ee
R (+)
S (+)
(–)
R (–)
R (–)
(+)
R (+)
(–)
R (–)
R (–)
S (+)
R (–)
R (–)
S (+)
S (+)
S (+)
S (+)
Conf. 584
583
620
C5
C4-12
R1
O
O
O
O
OEt
O
R2
Ketone
23 (1.1 mol%), 0°, THF, 4 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
23 (1.1 mol%), –30°, THF, 75 h
Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
107 (1.2 mol%)
Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),
Conditions
R1
I
O
OH
OH
OEt
OH +
OH I = 35% ee
I + II (45), I:II = 42:58,
80 (87) 24 h 0°
(60) 80% ee
II
OH
Me
2-C10H7
6 89 (81) 24 h
3 0°
64 (87) 24 h 20°
i-Pr
Ph Me
83 (81) 24 h
0°
Et
Ph
1-C10H7
86 (89) 24 h
20°
ClCH2
Ph
(69)
68 (89)
24 h
0°
Me
Ph
24 h
42 (82)
24 h
0°
Me
c-C6H11
20°
80
(89)
40 h
0°
Me
n-C6H13
t-Bu
95
(86)
24 h
0°
EtO2C(CH2)2 Me
Ph
76
(—)
96 h
0°
Me
t-Bu
56
(—)
24 h
0°
Me
i-Pr
24 h
% ee (—)
Time
0°
Me
Et
Temp
R2
R1
R2
OH
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
577
577
575
Refs.
621
C6
C5-17
t-Bu
R1
N
O
S
O
R2
O
MeC6H5, rt, 29 h
PhSiH3 (1.2 eq), CuF2 (1%), (S)-BINAP (1%),
n-C6H14, 65°, 1 h
PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),
2. PMHS, ketone, MeOH (3-7 eq), 15°, 17 h
MeOH, 60°, pyrrolidine, MeOH, THF
1. PhSiH3 (0.1 eq), 197 (2 mol%),
THF, –20°
[Rh(cod)]SbF6 (1 mol%), 126 (1 mol%),
Ph(1-C10H7)SiH2 (1.5 eq),
85 (10 mol%), MeOH, rt, 12-14 h
PMHS, Sn(OTf)2 (10 mol%), R1
I
t-Bu
OH
I (58) 2% ee
I (30) 53% ee
t-Bu
OH
R2
OH
(—) 90
–78°
121
—
–50°
124
% ee
OH
(97) 90
N
H
4h
S
Catalyst Temp Time
catalyst (0.05 mol%), MeC6H5, 4 h
PMHS (4 eq), CuCl/NaOBu-t (1 mol%),
(99) (99) (96)
CO2Me CO2Me CO2Me CO2Me
4-MeOC6H4 4-MeC6H4 4-O2NC6H4 1-C10H7
CH2-N-phth CH2-N-phth CH2-N-phth CO2Et
4-MeC6H4 4-ClC6H4 4-O2NC6H4 2-C4H3S
75% conversion, 20% eeb
(75) 98% ee
(98)
CH2-N-phth
Ph
(98)
(50)
(89)
(88)
(96)
CO2Me
2-C10H7
(98)
(98)
(99)
CO2Me
(98)
(75)
CO2Et
Ph Ph
Me
CO2Et Ph
R2 CF3
R1
784
783
587
576
385
590
622
C6
O
O
O
O
O
O
R
O
O
O
O
O
OMe
OEt
O
Ketone
23 (1.1 mol%), –30°, DME, 30 h
Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
23 (1.1 mol%), –30°, THF, 31 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
23 (1.1 mol%), –30°, THF, 14 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
MeC6H5, rt, 24 h
(R,R)-ebpe (20 mol%), vitride (3%),
PMHS (1.1 eq), Et2Zn (20 mol%),
44 (0.4 mol%), THF, rt, 30 min
Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),
108 (1.2 mol%), THF, 0°, 120 h
Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),
5-50°, 3-48 h
Et2SiH2, [(–)-(S)-bmpp]2RhCl, C6H6,
Conditions
I
O
OH
OH
I
O
OH
HO O
O
OH
O
+
OH
II
(74) 88% ee
(43) 32% ee
(—) 66% ee
OH
I = 97% ee
I + II (97), I:II = 75:25,
S
39
(76) 84% ee
S
31
(95)
t-Bu
Opt. Yield Conf. (93)
n-Bu
R
OEt
I (68) 37% ee
O
R
OH
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
577
577
577
594
787
575
785, 786
Refs.
623
S
O
O
O
O
O
I
90 88 70 78 74 67
12.5 100 0 12.5 100
121 121 122 122 122
S
91
0
121
131 (2 mol%), MeC6H5, rt, 4 h
OH
% ee
0
PMHS (1.2 eq), Ph2Zn (2 mol%),
OH
I (—) 78% ee
I (—)
+
II
(>99) 78% ee
(85) 92% ee
I = 70% ee
OH
OH
I + II (63), I:II 77:23,
OH
I (—) 90% ee
O
I
OH
124
MeC6H5 [(100 – x)]% x Ligand
NaOBu-t (3 mol%), THF (x%),
PMHS (4 eq), ligand (3 mol%), CuCl (3 mol%),
122 (0.05mol%), MeC6H5, –78°
PMHS (4 eq), CuCl/NaOBu-t (1 mol%),
121 (0.05 mol%), MeC6H5, –78°
PMHS (4 eq), CuCl/NaOBu-t (1 mol%),
124 (0.05 mol%), MeC6H5, –50°, 5 h
PMHS (4 eq), CuCl/NaOBu-t (1 mol%),
23 (1.1 mol%), 0°, DME, 55 h
Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
788
590
590
590
590
577
624
C6-12
C6-11
Ar
Ar
O
O
Me Me Et CH2Cl CO2Me t-Bu
2-C4H3S
Ph
Ph
Ph
Ph
Ph
Me
4-ClC6H4
Me Me Et CH2Cl CO2Me t-Bu
2-C4H3S
Ph
Ph
Ph
Ph
Ph Me Me Me Me Me
4-O2NC6H4
4-ClC6H4
4-MeC6H4
4-MeOC6H4
2-C10H7
1-indanone
R
Ar
R
Me
4-O2NC6H4
1-indanone
R
Ar
R
Ketone
70 h
70 h
70 h
70 h
50 h
170 h
170 h
25 h
70 h
40 h
70 h
70 h
Time
29 (5 mol%), MeOH, 0°
Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2, (2.5 mol%),
72 h
72 h
240 h
240 h
25 h
120 h
70 h
24 h
96 h
Time
29 (5 mol%), THF, 0°
Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (2.5 mol%),
Conditions
Ar
Ar
(24)
(0)
(0)
(51)
(92)
(15)
(11)
(95)
(68)
(28)
(46)
(100)
R
OH
(41)
(45)
(5)
(5)
(31)
(85)
(14)
(3)
(100)
R
OH
37
—
—
22
25
31
95
41
25
31
48
43
% ee
74
76
42
85
60
88
58
85
78
% ee
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
790
789
Refs.
625
C6-12
C6-11
R1
R1
4 10 43
(94) (95) (90)
Et2HSi Ph2HSi Ph2HSi
c-C6H11 c-C6H11 c-C6H11
i-Pr
n-Pr
t-Bu O
R2 Me Me Me Me Me Me Et Me Me Me n-Pr Me Me Me Me
R1
EtO2CCH2
EtO2C(CH2)2
AcO(CH2)3
Me2C=CHCH2CH2
n-C6H13
2-ClC6H4
Ph
Bn
2-MeO2CC6H4
3-AcOC6H4
Ph
2-MeOBn
BnCH2
1-C10H7
2-C10H7
Time 24 h 7h 24 h 20 h 2h 4h 4h 5h 14 h 24 h 5h 4h 5h 5h 6h
Temp –5° 0° 20° 20° 0° 0° 5° 0° 0° 0° 0-5° –5° 0° –5° –5°
x 6.0 6.0 6.0 6.0 4.0 4.0 4.0 6.0 6.0 6.0 4.0 6.0 6.0 4.0 4.0
AgBF4 (0.02 mol%), THF
(93)
(87)
(92)
(95)
(82)
(81)
(95)
(95)
(73)
(74)
(85)
(94)
(85)
(91)
(60)
R2
93
94
66
82
82
92
96
71
91
94
63
70
68
95
27
% ee
11
(98)
Et2HSi
c-C6H11
n-Pr
R1
40
(92)
Ph2HSi
c-C6H11
Me
Ph2SiH2 (1.6 eq), 87 (x mol%), 99 (10 mol%),
9
(98)
Et2HSi
n-C6H13
Me
R2
12
OH
25
(99)
Et2HSi
i-Bu
Me
R
R
S
R
R
R
R
R
Opt. Yield Conf. (98)
R3Si Ph2HSi
t-Bu
R2
OH
R2
5-50°, 3-48 h
R1
Me
R2
R3SiH, [(+)-(R)-bmpp]2RhCl, C6H6,
R1
O
580, 581
785
626
C7
C6-12
O
O
O
O
R
88
(99)
2-C10H7 Me
O
R
60
(92)
n-C7H15 Me
23 (1.1 mol%), –30°, THF, 94 h
Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
23 (1.1 mol%), –30°, THF, 75 h
Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
AgBF4 (2 mol%), THF, 0°, 1 d
Ph2SiH2 (1.3 eq), RhCl3 (1 mol%), 197 (5 mol%),
2. PMHS, ketone, MeOH (3-7 eq), 15°, 11 h
OH
OH
I
I
OH
II +
OH
OH
OH
I = 89% ee
II
OH
I = 35% ee
I + II (45), I:II = 42:58,
I + II (88), I:II = 41:59
II 1S,2R 89% ee
OH
I + II (75), I:II = 69:31,
OH
+
I 1S,2S 91% ee
OH +
S
23
(12)
Et
Ph
(92) 50% ee
S
8
(19)
ClCH2
Ph
OH
R
91
(100)
Me
Ph
pyrrolidine, MeOH, THF, 60°
R
89
(45)
c-C6H11 Me
1. PhSiH3 (0.1 eq), 197 (2 mol%),
R
87
O
Conf.
% ee
R2
OH
(100)
R1
Me
38 (0.5 mol%), Et2O, rt, 15-25 h
Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (0.25 mol%),
t-Bu
R2
Product(s) and Yield(s) (%)
R2
O
Conditions
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
R1
R1
Ketone
577
577
390
587
571
Refs.
627
S
O
EtO
O
N
O
O
O
O
OMe
OEt
O
18 h 4h —
10° 10° 30°
101 103 104
NaOBu-t (1 mol%), THF/MeC6H5, –50°, 4 h
PMHS (4 eq), 124 (0.05 mol%), CuCl (1 mol%),
7h
Time
0°
100
Complex Temp
AgBF4 (0.02 mol%), THF
complex (10 mol%),
Ph2SiH2 (1.6 eq), 87 (4.0 mol%),
108 (1.2 mol%), THF, 0°, 24 h
Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),
108 (0.4 mol%), THF, rt, 30 min
Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),
126 (1 mol%), THF, –20°
[Rh(cod)]SbF6 (1 mol%),
Ph(1-Np)SiH2 (1.5 eq),
23 (1.1 mol%), –30°, THF, 425 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
O
S N
HO
(0)
(80)
(79)
(82)
OH
O
OH
EtO
O
OH
(66) 52% ee
—
75
79
94
(94) 99% ee
(71) 74% ee
OEt
(74) 69% eeb
(80) 98% ee, syn:anti = 1:1
OMe
OEt
% ee
O
O
OH
O
590
580
575
787
576
577
628
C8
C7
O
N
N
N O
O
O
Ketone
1 (1.1 mol%), THF, –50°, 48 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),
38 (0.5 mol%), Et2O, 0°, 25 h
Ph2SiH2 (1.5 eq), [Ir(cod)Cl]2 (0.25 mol%),
NaOBu-t (1 mol%), THF/MeC6H5, –78°, 6.5 h
PMHS (4 eq), 124 (0.05 mol%), CuCl (3 mol%),
NaOBu-t (1 mol%), THF/MeC6H5, –35°, 8 h
PMHS (4 eq), 124 (0.05 mol%), CuCl (3 mol%),
MeOH, rt, 12-14 h
PMHS, Sn(OTf)2 (10 mol%), 87 (10 mol%),
NaOBu-t (1 mol%), MeC6H5, –50°, 2 h
PMHS (4 eq), 124 (0.05 mol%), CuCl (1 mol%),
Conditions
N
I
OH
OH
OH
I (82) 77% ee
HO
N
N
N
OH (19) 19% ee
(97) 84% ee
(92) 75% ee
(99) 0% ee
(97) 90% ee
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
578
582
590
590
385
590
Refs.
629
O
II
37 33 50 49
0° 10° 27°
117 118 119
3. Add ketone, 4 d
2. PMHS (5 eq)
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
25 (1.1 mol%), THF, rt, 10 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),
II (67) 24% ee
I (62) 80% ee
% ee
0°
I (—)
OH
I (90) 92% ee
Temp
Ligand
OH
I (>98) 23% ee
I
116
ligand (0.5 %), MeC6H5
Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5 %),
46 (0.4 mol%), THF, rt, 30 min
Ph2SiH2 (1 eq), [Rh(cod)Cl]2, (0.3 mol%),
THF, –20°
[Rh(cod)]SbF6 (1 mol%), 126 (1 mol%),
Ph(1-Np)SiH2 (1.5 eq),
2. PMHS, ketone, MeOH (3-7 eq), 15°, 6 h
MeOH, THF, 60°
1. PhSiH3 (0.1 eq), 197 (2 mol%), pyrrolidine,
MeC6H5, rt, 24 h
(R,R)-ebpe (20 mol%), vitride (3%),
PMHS (1.1 eq), Et2Zn (20 mol%), (—) 20% ee
588
606
791
788
576
587
594
630
C8
Ph
O
O
O
O OEt
Ketone
none none THF THF THF CH2Cl2 CCl4 THF
41 41 41 41 40 40 39 51
Ligand Solvent
II
OH
I
O OEt
73 (79) (54) (86) (77) (70) (58) (45)
–40° 0° –78° –78° –78° 0° –78°
0
14
48
51
82
73
73
% ee (54)
0°
II
Product(s) and Yield(s) (%)
(85) 86% ee
(>99) 76% ee
(80) 98% ee
(70) 88% ee
I (94) 60% ee
Ph
Ph
OH
OH
OH
Temp
Ph2SiH2 (4 eq), [Rh(cod)Cl]2 (1 mol%), ligand
[Rh(cod)Cl]2 (0.5 mol%), 37 (0.5 mol%), 0°
Ph2SiH2 (1.5 eq),
[Rh(cod)Cl]2 (1 mol%), 41, THF, –78°
Ph(1-Np)SiH2 (4 eq),
131 (2 mol%), MeC6H5, rt, 48 h
PMHS (1.2 eq), (i-Pr)2Zn (2 mol%),
23 (1.1 mol%), –30°, THF, 24 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (0.5 mol%),
25 (1.1 mol%), –40°, THF, 26 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
Conditions
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
792
570
792
788
577
577
Refs.
631
(78) (85)
11 h 48 h 9h
25 26 27
(97) (94) (95) (65) (93) (55) (56) (97) (33) (99) (99) (92) (85) (78)
10° 0° rt rt rt rt rt rt rt –40° rt rt rt
41 41 42 47 49 50 45 44 46 46 43 53 52
(92)
Ph
OH
rt
rt
Temp
1 15
3
0
26
86
79
17
69
4
2
52
40
82
81
73
44
R
—
R
R
R
S
R
S
R
R
R
R
R
R
R
% ee Conf.
II (91) 76% ee
41
40
Ligand
ligand (0.4 mol%), THF, 30 min
Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),
6 (0.4 mol%), THF, rt, 30 min
Ph(1-Np)SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),
92
(88)
5h 92
% ee (89)
Time
24
I
Ligand
ligand (1.1 mol%), THF, rt
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),
787
787
606
632
C8
Ph
O
Ketone
2 4
50°
% ee 94 90 95 96
Time 5h 1h 6h 99)
(99)
(90)
PhSiH3
16 h
24 h
1h
40 h
2h
6h
2h
16 h
2h
8h
Time
I
I (94) 76% ee
I (100) 72% ee
Silane
Silane (1.5 eq), 126 (1 mol%), THF, rt
Ar
2
Ar
4
CuF(PPh3)3•MeOH
[(Ph3P)CuH]6
Ar
4
CuF(PPh3)3•MeOH, dppb
Ar
(—)
0.5
CuF2
1
air
1
CuF2
CuI, Ph3SiF2N(Bu-n)4
Ar
4
CuF2
air
air
2
CuF2, dppb
2
Ar
2
CuF2, dppb
CuF(PPh3)3•MeOH
atm
x
[Cu]
(S)-BINAP, MeC6H5, atmosphere, rt
PhSiH3 (1.2-1.5 eq), [Cu] (x mol%),
(S)-BINAP (4 mol%), MeC6H5, air, rt
Me(EtO)2SiH (1.5 eq), CuF2,
MeC6H5, Ar, rt
PMHS (5 eq), CuF2, (S)-BINAP (4 mol%),
576
784
784
784
638
C8
Ph
O
Ketone
(87) (85) (13) (86) (30) (18)
OPr-i OPr-i OPr-i F F F
51 59 62 59 60 61
62
(89) (50) (90)
128 129 130
86
20
51
% ee (36)
127
51
56
61
65
51
18
Ligand
ligand (1 mol%), THF, rt
I
(20)
Cl
57
Ph2SiH2 (1.5 eq), [Rh(cod)]SbF6 (1 mol%),
50
Cl 23
% ee (60)
X
I
51
Ph
OH
L
(EtO)3SiH, THF, Ti(L)2X2, 2-3 d
Conditions
R
R
S
S
Conf.
S
S
S
S
S
S
S
R
Conf.
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
576
793
Refs.
639
18 h 18 h 170 h 48 h 216 h 288 h 40 h 44 h 18 h 72 h
131 135 139 137 147 138 151 136 149 150
93
(59) (46) (42) (38) (52) (34)
24 h 24 h 24 h 5h 36 h 24 h 70 h
Cu(OTf)2 — AgOTf Cu(OTf)2 AgOTf AgOTf
37 37 35 35 36 41
84
45
92
90
67
95
% ee (56)
Time
84
83
67
78
91
25
37
84
75
88
% ee
AgOTf
OH
(>99)
(>99)
(78)
(56)
(66)
(30)
(11)
(56)
(99)
(98)
37
Ph
Ph
OH
Ligand Additive
ligand (1 mol%), additive (1 mol%), Et2O, 0°
Ph2SiH2 (2 eq), (Ph3P)RuCl2 (1 mol%),
Time
Ligand
ligand (2 mol%), MeC6H5, rt
PMHS (1.2 eq), Et2Zn (2 mol%),
R
S
R
R
R
R
R
R
S
S
Conf.
569
794
640
C8
Ph
O
Ketone
rt rt rt rt rt 0° 0° 0°
none C6H6 Et2O DME CH2Cl2 MeCN THF THF THF
29 29 29 29 29 29 29 28 30
Temp 15° 0° 40° 15° 0° –20° 15° 0°
Ligand 28 28 29 29 29 29 30 30
ligand (5 mol%), THF
144 h
20 h
24 h
24 h
1h
4h
144 h
20 h
Time
Ph2SiH2 (1.5 eq), [Ir(cod)Cl]2 (2.5 mol%),
rt
Solvent
Ligand
Temp
[Rh(cod)2]BF4 (5 mol%), ligand (5 mol%)
Conditions
72 h
72 h
48 h
20 h
12 h
3h
2h
12 h
1h
Time
Ph
Ph
15 13 0 23 18 0 0 22
(43) (100) (100) (55) (40) (90) (81)
% ee
50
31
85
0
6
0
8
21
12
% ee
(82)
OH
(67)
(46)
(31)
(43)
(100)
(100)
(71)
(100)
(73)
OH
R
—
—
S
S
—
R
R
Conf.
R
R
R
—
S
—
R
S
R
Conf.
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
789
789, 795
Refs.
641
92 98 —
MesPhHSi Mes2HSi
95 — — —
(—) (—) (0) (0) (0)
Ph2SiH2 Ph(1-Np)SiH2 Ph(t-Bu)SiH2 Et3SiH PMHS
58 (78) (50) (30) (50)
93 87 88 94 96
58
44
13
54
% ee (95)
Ligand
ligand (10 mol%), MeOH, rt
OH
88
(—)
PhMeSiH2
PMHS, Sn(OTf)2 (10 mol%),
0 78
(—)
% ee
I (—)
PhSiH3
Silane
Ph
95
(2-MeC6H4)2HSi
Silane (1.5 eq), 126 (1 mol%), THF, rt
80
1 66
PhMeHSi Ph2HSi
8
Et2HSi
2-MeC6H4PhHSi
3
% ee
PhH2Si
I
Ph
OH
n-C8H17H2Si
R3Si
R3SiH{RhCl(cod)}2 (2.5 mol%), (–)-37, THF, rt
R
R
S
S
R
Conf.
385
576
586
642
C8
Ph
O
Ketone
16
(26) (30) (73) (81) (36) (25) (51) (39) (52) (44) (65) (73) (50) (73) (35) (83)
13 15 14 9 10 8 12 11 32 33 3 4 5 6 191 192
0
5
24
32
27
31
40
33
36
0
35
12
16
8
18
40
% ee (51)
II
7
Ph
OH
Ligand
ligand (1 or 2 mol%), THF, 0°, 20 h
Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (0.5 mol%),
Conditions
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
789
Refs.
643
Time 70 h 40 h 40 h
Temp 0° 0° 0°
28 30
76
(76) (80) (76) (84)
2.4 2.4 2.4 4
THF Et2O MeC6H5 MeC6H5 94
93
91
85
% ee (64)
x
27
10
48
% ee
2.4
(72)
(56)
(46)
none
II
II
Solvent
48 (x mol%), 0°
Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (1 mol%),
Ligand 29
ligand (5 mol%), MeOH
Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (2.5 mol%),
585
790
644
C8
Ph
O
Ketone
R R R R R R R
58.3 31.0 7.5 33.1 27.6 25.7
94 90 78 92 83 79
218 218 218 218 218
RhClL2 [Rh(Cl)COL2] 1/2[RhCl(C2H4)2]2•2L + C2H4 1/2[RhCl(C2H4)2]2•4L 1/2[RhCl(C2H4)2]2•5L
1/2[RhCl(C2H4)2]2•3L 219
218
1/2[RhCl(C2H4)2]2•3L
S
217
1/2[RhCl(C2H4)2]2•2L 51.2
R
219
1/2[RhCl(C2H4)2]2•2L 89
R
41.4
96
218
1/2[RhCl(C2H4)2]2•2L R
R
5.0
88
218
[RhCl(C2H4)•L]2
3.3
R
6.6
92
218
1/2[RhCl(C2H4)2]2•L
63
R
6.8
93
217
1/2[Rh(Cl)(cod)]2•2L
52.3
R
4.4
94
219
1/2[Rh(Cl)(cod)]2•2L
92
—
11.2
93
218
1/2[Rh(Cl)(cod)]2•2L
R
0
Conf.
90
219
[Rh(Cl)(cod)]•2L
% Conv. % ee
II
4.4
218
[Rh(Cl)(cod)]•L
Ph
OH
Product(s) and Yield(s) (%)
86
Ligand
Catalyst
ligand, THF, rt, 24 h
Ph2SiH2 (1.3 eq), catalyst (1 mol%),
Conditions
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
796
Refs.
645
S R S S S S S S S S
CONHPh CONHPh CONHC10H7-1 CONHCHPh2 CONHC6H14-n CONHBu-t CO2Ph CO2Me CO2Bu-t CH2OBn
1:3 1:1 1:1
(S,S,S)-TRISPHOS (S,S,S)-TRISPHOS
[Rh(cod)Cl]2 [Rh(cod)Cl]2 (NBD)Rh(acac) (S,S,S)-TRISPHOS (NBD)RhClO4 (S,S,S)-TRISPHOS
1:2
1:2
TRISPHOS
[Rh(cod)Cl]2
Rh:Ligand
Ligand
Catalyst
Ph2SiH2 (1 eq), catalyst, ligand, C6H6, rt, 16 h
Conf.
R
CH2Cl2, 0° to rt, 24 h
R N Cl3SiH (1.5 eq), CHO (0.1 eq),
II
II
(65)
(67)
(53)
(38)
(60)
(29)
(88)
(39)
(53)
(80)
(82)
(69)
(78)
(93)
(90) 36:64 71:29 61:39 54:46 55:45 61:39 57:43 55:45 56:44
31 27 43 20 8 11 21 14 11 13
81
58
75
81
0
% ee
R:S 65:35
% ee
797
379
646
C8
Ph
O
Ketone
0° 0° 0°
Et2O/TMEDA 2:1 THF/TMEDA 2:1 Et2O, TMEDA
(EtO)3Si (EtO)3Si (EtO)3Si
87 87 88 87
103 99 99 102
7h
3h
2h
2h
3h
Time
Ligand 89 88 92 93 91
Complex 100 101 103 104 102 20°
20°
10°
0°
–5°
Temp
20 h
18 h
2h
18 h
10 h
Time
ligand (10 mol%), AgBF4 (0.02 mol%), THF
Ph2SiH2 (1.6 eq), complex (4.0 mol%),
89
Ligand
99
Complex
24h
24 h
24 h
6 h; 16 h
6 h; 16 h
Time
ligand (10 mol%), AgBF4 (0.02 mol%), THF
Ph2SiH2 (1.6 eq), complex (4.0 mol%),
0°; 20°
Et2O
(EtO)3Si
Temp –78°; 20°
Solvent
(MeO)3Si THF
R3Si
R3SiH (1 eq), Li-(R)-BINOL (5 mol%)
Conditions
I
I
Ph
64 33 63
(50) (52) (46)
31 62 84 87
(94) (88) (94) (87)
91 83 54 19 —
(91) (92) (88) (82) (66)
% ee
22
(94)
% ee
0 31
(33)
% ee (88)
I
OH
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
580
580
592
Refs.
647
52 55 54 56 55 82
10° 20° 20° 20° 20°
117 118 119 109 113
96 95 39 88 79 95 86 86 97 96
10° 20° –27° 0° 10° 0° 20˚ 10° 10° 10°
1:1 1:1 1:1 1:1 1:1 1:1 1:1 1:1 1:4 1:2
MeC6H5 THF THF THF C6H6 C6H6 MeC6H5 MeC6H5 MeC6H5
96
0°
1:1
MeC6H5 MeC6H5
57
–27°
1:1
MeC6H5
Solvent Rh[(NBD)Cl]2:117 Temp
Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%), 117
% Conv.
% ee
0°
Ligand
Temp
I
I
116
ligand (0.5%), MeC6H5
Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),
56
56
54
49
46
49
52
15
51
55
53
17
% ee
791
791
648
C8
Ph
O
Ketone
Time — 26 h 4d
–5° to 0° 0° 0°
Ph2HSi PhMeHSi Ph(1-Np)HSi
50°
MeC6H5 40°
50°
Et2O none
Temp
Solvent
12 h
5h
5h
Time
(EtO)3SiH, 194 (10 mol%)
R3Si
Temp
99 (10 mol%), THF, –5° to 0°
R3SiH (1.6 eq), 87 (1.5 mol%),
Conditions
I
Ph
(>98)
(78)
% ee
54
48
55
% ee
62
14
76-78
(>98)
(62)
(32)
(—)
I
OH
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
378
580
Refs.
649
(22)
(90) (47) (47)
24 h
24 h 24 h 24 h
–20° 20° 0° 0° 0° 0° 0° 0° 0°
Et2O/TMEDA 30:1 Et2O/TMEDA 30:1 Et2O/TMEDA 30:1d Et2O/TMEDA 30:1e Et2O/TMEDA 30:1f Et2OTMEDA 30:1f Et2O Et2O/TMEDA 30:1 Et2O/TMEDA 30:1g
Li-(R)-2,2'-Me2BINOL Li-(R)-methoxythio-BINOL Li-(R)-BINOL Li-(R)-BINOL Li-(R)-BINOL Li-(R)-BINOL Li-(R)-BINOL (R)-hydro-BINOL Li-(R)-BINOL
x 0.3 0.3 0.33 0.48 0.5 0.24
Catalyst CuOBu-t CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh
ligand (y mol%)
(–)-BPPFA
(+)-NORPHOS
(+)-NORPHOS
(–)-DIOP
0-20°
20°
20°
0-20°
0-20°
0-20°
(–)-DIOP (–)-DIOP
Temp
Ligand
18 h
120 h
95 h
16 h
23 h
15 h
Time
(100)
(67)
(51)
(100)
(100)
(100)
(87)
24 h
20°
Et2O or THF
Al-BINOL complex
Ph
(0)
24 h
20°
Et2O/TMEDA 30:1c
Li-(R)-BINOL
Ph2SiH2 (1.7 eq), catalyst (x mol%),
(46)
24 h
20°
Et2O/TMEDA 2:1c
Li-(R)-BINOL
OH
(37)
48 h
–22°
THF
(R)-BINOL phosphoric acid
28.9
16.3
38.8
13.4
18.7
19.5
% ee
24 h
24 h
8h
8h
R
S
R
R
R
R
Conf.
(91)
(92)
(96)
(91)
(50)
(53)
12 h
0°
Et2O/TMEDA 2:1c
Li-(R)-BINOL 24 h
7
66
40
52
70
70
59
58
37
26
—
63
64
6
48
% ee
48 h
0°
Et2O
(59)
Time
Temp
Solvent
Li-(R)-BINOL
Ph
OH
Catalyst
(MeO)3SiH (1 eq), catalyst
S
S
S
S
S
S
S
R
R
S
S
R
S
R
Conf.
798
592
650
C8
Ph
O
Ketone
Li-phenylalanine
(EtO)3Si Ph2SiH2 (1.7 eq), catalyst (x mol%),
x 0.3 0.55 0.4 0.3 0.16 0.04 0.3 0.33 0.48 0.5 0.24
Catalyst CuOBu-t CuOBu-t CuOBu-t CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh
0.39
0.15
0.08
0.19
0.30
0.44
0.34
(–)-BPPFA
0.27
(+)-NORPHOS 0.81
(+)-NORPHOS 0.71
(–)-DIOP
(–)-DIOP
(–)-DIOP
(–)-DIOP
(–)-DIOP
(–)-DIOP
(–)-DIOP
(–)-DIOP
0-20°
20°
20°
0-20°
0-20°
0-20°
–10°
0-20°
0-20°
0-20°
0-20°
18 h
120 h
95 h
16 h
23 h
40 h
23 h
16 h
15 h
20 h
15 h
Time
OH
Li2-histidine
(EtO)3Si
Temp
(25)
Li-histidine
(MeO)3Si
y
(26)
189
(EtO)3Si
0.35
(26)
190
(EtO)3Si
Ligand
(30)
none
Ph
(0) (26)
188
(MeO)3Si
ligand (y mol%)
(55)
Ligand
I
(EtO)3Si
Ph
OH
R3Si
R3SiH, ligand, THF/TMEDA, 0°, 10 min
Conditions
28.9
16.3
(67)h (100)
38.8
13.4
(100)h (51)
18.7
16.7
16.9
12.7
15.3
18.8
19.5
% ee
(100)
(100)
(100)
(100)
(100)
(100)
(100)
R
S
R
R
R
R
R
R
R
R
R
Conf.
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
493
798
593
Refs.
651
CCl4
4.4 4.4 4.4 4.4 4.4 8.8
125 125 125 125 (R)-BINAP 87
12 21
(92) (24)
DME MeC6H5
x — 2.0 2.0 1.0 1.5 1.5
Additive none AgBF4 AgPF6 AgOTf BF3•OEt2 EtAlCl2
— 3h 5h 27 h 14 h 18 h
rt 0° –3° –5° 0° 0°
Temp Time
additive (x mol%), THF
(89)
(90)
(96)
(80)
(94)
(0)
67
82
89
87
95
—
% ee
12
(11)
CCl4
Ph2SiH2 (1.6 eq), 99 (10 mol%),
10
OH
63
% ee (8)
Ph
Ph
OH
(16)
(95)
(97)
(45)
(—)
72 h
24 h
24 h
96 h
(88)
(0)
(94)
MeCN
none
none
THF
dioxane
24 h
24 h
48 h
Time
I
THF
Solvent
Ph2SiH2, 207 (1 mol%), rt
none
125 MeC6H5
Solvent
x 8.8
Ligand
ligand (x mol%), AgOTf (2 mol%)
[RuCl2(C6H6)]2 (0.5 mol%),
Ph2SiH2 (160 mol%),
R
R
S
R
R
Conf.
0
5 (R)
54
35
23
—
38
% ee
580, 581
800
799
652
C8
Ph
O
Ketone
39.8
(66) (60) (45) (48) (60) (51) (53) (71) (72) (76) (93) (63)
MeC6H5 C6H6 n-C5H12 PE Et2O THF dioxane CH2Cl2 ClCH2CH2Cl CHCl3 CCl4 MeCN 16.8
56.6
15.2
22.2
23.8
25.2
24.0
34.0
24.2
28.4
31.0
31.8
% ee (60)
none
Ph
OH
Solvent
66 (2.5 mol%), 0-20°, 18 h
Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.5 mol%),
Conditions
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
801
Refs.
653
25.5 31.8 34.4 20.2 23.0 37.4 32.8 39.8 70.1 26.5 33.8 39.6 3.6 4.3 4.2 34.7 33.8 53.6 8.7 24.3 1.7
(66) (66) (40) (56) (77) (44) (63) (77) (63) (69) (58) (57) (19) (16) (66) (69) (68) (51) (69) (48)
65 66 67 69 68 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84
% ee (42)
Ph
OH
64
Ligand
ligand (2.5 mol%), MeC6H5, 0-20°, 18 h
Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.5 mol%),
R
R
R
S
R
S
R
S
R
R
S
S
R
R
R
R
R
S
R
S
R
Conf.
804
654
C8
Ph
O
Ketone
40.7
(93) (75) (90) (85) (67) (89) (90) (70) (85) (95) (10) (27) (63) (90) (90) (89) (17) (49) (22)
66 67 69 68 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84
7.6
46.5
10.4
65.6
50.8
49.6
9.0
5.6
42.9
62.4
50.0
66.6
83.4
71.6
69.8
62.2
53.2
52.6
56.6
% ee (80)
64
Ph
OH
Ligand
ligand (2.5 mol%), CCl4, 0-20°, 18 h
Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.5 mol%),
Conditions
R
R
R
S
R
S
R
S
R
R
S
S
R
R
R
R
R
S
S
R
Conf.
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
801
Refs.
655
5 5 5 5 5 5
58 55 55 56 56
6
54 2.5
5
54
58
5
54
58
x
Ligand or complex
ligand or complex (x mol%), rt
CCl4
MeC6H5
CCl4
MeC6H5
CCl4
CCl4
MeC6H5
CCl4
MeC6H5
none
Solvent
Ph2SiH2 (1.2 eq), [Rh(cod)Cl]2 (0.5 mol%), Ph
(—)
(72)
(21)
(68)
(59)
(—)
(48)
(—)
(61)
(36)
OH
33
50
3
9
84
15
5
55
1
7
% ee
802
656
C8
Ph
O
Ketone
18 h 6h 6h 6h 4h 18 h
131 134 132 133 152 148
21 h 168 h 4h 50 h
THF THF THF THF DME CH2Cl2 MeC6H5 THF
24 25 26 27 25 25 25 25
9h
78 h
11 h
5h
24 h
THF
23
Time
Solvent
Ligand
ligand (1.1 mol%), –40°
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
Time
Ligand
ligand (2 mol%), MeC6H5, rt
PMHS (2 eq), Et2Zn (2 mol%),
Conditions
Ph
Ph
(95)
(86)
(81)
(96)
(85)
(78)
(88)
(89)
(90)
OH
(>99)
(15)
(68)
(14)
(94)
(>99)
OH
89
90
91
90
15
1
92
92
85
% ee
88
0
22
76
78
76
% ee
S
S
S
S
S
R
S
S
S
Conf.
R
—
S
S
S
S
Conf.
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
499
577
788
Refs.
657
C8-9
Ar
Ph
O2N
O
O
AgOTf AgBF4 none AgBF4
2 2 2 4
Rh(cot)Cl Rh(cot)Cl RhCl3 RhCl3 5°
rt
15°
15°
20°
I
I
CF3
OH
90
75
70
43
41
% ee
97 91 93 21
(97) (98) (99)
7h 3h 4h
4-ClC6H4 4-MeC6H4 4-MeOC6H4
% ee (98)
OH
CF3
7h
Ar
Ph
OH
I (9) 6% ee
Ph
O2N
(98)
(86)
(57)
(64)
(68)
I
Time
2h
2h
3h
3h
2h
Time
Ph
63 (0.5 mol%), THF, 0°
Ph2SiH2 (1.6 eq), [Rh(cod)Cl]2 (0.25 mol%),
161 (2 mol%), MeC6H5, rt, 1 h
PMHS (1.2 eq), Et2Zn (2 mol%),
MeC6H5, 65°, 1 h
PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),
MeC6H5, 65°, 1 h
PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),
(EtO)3SiH, 193 (10 mol%)
none
2
Rh(cot)Cl
Temp
Ph
OSiPh2H
Ar
CF3
O
AgX
x
Catalyst
95 (x mol%), AgX (2 mol%), THF
Ph2SiH2 (1.5 eq), catalyst (1 mol%), II
OSiPh2H
(—) 54% ee
Ph
(>99) 27% ee
(9) 5% ee
OH
(2)
(14)
(39)
(33)
(32)
II
+
579
788
783
783
378
572
658
C8-9
Ar
Ar
O
O
16 16 17 18 19 17 20 21
Me Et Me Me Me Me Me Me
Ph
Ph
Ph
Ph
4-ClC6H4
Ph
Ph
2h
98)
OH
(90)
(96)
(99)
(84)
(100)
(100)
(40)
(87)
Ph
R
(77)
(78)
(84)
(100)
Ar
OH
R Time
(EtO)3SiH, 194 (10 mol%), Et2O
2h
199
O
Time
Catalyst
Ph
n-BuLi (0.010 eq to catalyst), THF, –78° to rt
(EtO)3SiH (2.5 eq), catalyst,
Ar
O
40
20
6
13
2
32
5
0
14
7
5
12
% ee
S
S
R
S
S
S
S
—
S
S
R
S
Conf.
378
806
668
C8-12
R1
R
(98)
24 h
2-C10H7
R2 Me Et Me Me Me Me
R2 Me Me Me Me Me Et Me
R1
Ph
Ph
(E)-PhCH=CH
c-C6H11
n-C6H13
1-C10H7
R1
Ph
4-MeOC6H4
4-CF3C6H4
2,4-Me2C6H3
2,4,6-Me3C6H2
Ph
1-C10H7
(–)-34, THF, rt
MesPhSiH2, [Rh(cod)Cl]2 (2.5 mol%),
48 (4 mol%), MeC6H5, rt
R1
(85)
30 h
1-C10H7
Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (1 mol%),
(93)
48 h
4-BrC6H4
R2
(93)
72 h
3-BrC6H4
R2
98 97 96 95 98 98 99
(97) (88) (97) (99) (96) (97)
% ee
92
52
87
22
91
94
% ee
66
48
55
62
57
54
% ee
(94)
R2
OH
(90)
(90)
(85)
(83)
(91)
(84)
I
OH
(87)
72 h
2-BrC6H4
O
(97)
R1
R
OH
24 h
125 (2.2 mol%), AgOTf (2 mol %), THF, rt Time
Ph2SiH2 (160 mol%), [RuCl2(C6H6)]2 (0.5 mol%),
Conditions
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
Ph
R
O
Ketone
586
585
799
Refs.
669
C8-13
R
1
R
30 40 70 — — 30 5 5
(80) (89) (90) (90) (95) (82) (78)
Me Me Me Ph Ph Ph Ph
4-MeOC6H4
Bn
Ph
4-CF3C6H4
4-MeC6H4
4-MeOC6H4
26
4-MeC6H4
26
(85) (86)
Me
Ph
% ee (70)
R2
Me
Me
Ph
THF/TMEDA, 0°, 24 h
4-CF3C6H4
R2
R1
R
96
OH
82
(92)
1-Ad
2
94
(98)
BnCH2
O
72
(91)
% ee
c-C6H11
R1
R
OH
(81)
(MeO)3SiH (1 eq), Li2-histidine (10 mol%),
34, THF, 0°
o-Tol2SiH2, [Rh(cod)Cl]2 (1.0 mol%),
n-C6H13
R
O
593
586
670
C8-14
C8-13
(90) (95)
PhMe2Si Et2HSi
c-C6H11
c-C6H11
R Me Me Me Me Me Me Me Me Me Et i-Bu Bn
Ar
Ph
2-MeC6H4
4-MeC6H4
2-MeOC6H4
4-MeOC6H4
2-ClC6H4
4-ClC6H4
1-C10H7
2-C10H7
Ph
Ph
Ph
126 (1 mol%), THF, –20°
Ar
(92)
PhMe2Si
t-Bu
R
(97)
EtMe2Si
t-Bu
Ar
(93)
PhMeHSi
i-Pr
(75)
(95)
(95)
(99)
(99)
(95)
(90)
(56)
(90)
(90)
(98)
(80)
R
OH
(96)
Ph2HSi
i-Pr
Ph(1-Np)SiH2 (1.5 eq),
(98)
Ph2SiH2
Et
O
1%
94
94
94
95
98
85
98
88
95
92
95
95
ee (%)
19%
58%
54%
56%
12%
16%
42%
Opt. Yield (97)
R
R3Si
Ph
Et2HSi
C6H6, 5-50°, 3-48 h
OH
R
S
S
R
S
S
R
R
Conf.
Product(s) and Yield(s) (%)
Me
R
R3SiH, [(+)-(R)-bmpp]2RhCl,
Conditions
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
R
Ph
O
Ketone
576
785
Refs.
671
C8-14
(50) (61)
Cl H Me OMe H Ph
4-BrC6H4
4-EtC6H4
4-BrC6H4
4-BrC6H4
4-i-PrC6H4
4-BrC6H4
(58)
(53)
(60)
(50)
H
4-BrC6H4 (61)
R
Ar
—
—
S
R
S
S
R
S
S
Conf.
75
85
78
80
84
65
83
S
S
R
R
R
R
R
% ee Conf.
0
(90)
24 h
Ph
4-CF3C6H4
R
0
(74)
24 h
Ph
4-MeC6H4
Ar
77
(67)
24 h
Me
1-C10H7
(EtO)3SiH, THF, 198, 96 h
90
(57)
24 h
Me
2,4,6-Me3C6H2
R
81
(60)
24 h
i-Bu
Ph
Ar
65
(63)
24 h
MeO2C(CH2)2
Ph
OH
46
(74)
24 h
Me
BnCH2
O
66
(91)
24 h
% ee
Me
R2
OH
61
2-BrC6H4
R
1
(80)
Time
Li-(R)-BINOL (5 mol%), 0°
(MeO)3SiH (1 eq), Et2O:TMEDA (30:1),
6h
Me
Ph
R2 R2
O
R1
R1
793
572
672
C9
C8-15
Ar
CF3
Ar
t-Bu Me i-Pr t-Bu Me i-Pr t-Bu
Ph
2-C10H7
2-C10H7
2-C10H7
1-C10H7
1-C10H7
1-C10H7
O
i-Pr
Ph
O
Me
Ph
O
R
R
Ar
O
Ketone
vitride (3%), MeC6H5, rt, 24 h
(R,R)-ebpe (20 mol%),
PMHS (1.1 eq), Et2Zn (2 mol%),
MeC6H5, or THF, or MeC6H5/THF, –78°
PMHS (5 eq), CuCl, t-BuONa, 121 (0.005 mol%),
vitride (3%), MeC6H5, rt, 24 h
(R,R)-ebpe (20 mol%),
PMHS (1.1 eq), Et2Zn (2 mol%),
vitride (3%), MeC6H5, rt, 24 h
(R,R)-ebpe (20 mol%),
PMHS (1.1 eq), Et2Zn (20 mol%),
(MeO)3SiH (1.2 eq), 178, THF, 0°, 20 h
Conditions
S S S S S S —
65 82 20 22 20 —
(93) (>95) (>95) (59) (50) (0)
Ar
CF3 OH (—)
OH
S
12
(59)
I
S
42
(95)
4-MeOC6H4
3-MeOC6H4
Ar
(85) 95% ee
(—) 71% ee
Conf.
28
II
R
(93)
Ar % ee
OH
+
OH
72
73
% ee
Product(s) and Yield(s) (%)
I + II
I
R
I (—) 66% ee
Ar
OH
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
594
589
594
594
807
Refs.
673
Ph
O
II
OH
I
% ee 37 35 45 46 56 66
0° 20° 0° 20° 20° 20°
117 118 119 109 113
Ligand
Temp
I (—)
I (99) 88% ee
II (96) 95% ee
Ph
Ph
OH
116
ligand (0.5%), MeC6H5
Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),
1 (1.1 mol%), THF, –40°, 24 h
[Rh(cod)2]BF4 (1 mol%),
(3-FC6H4)2SiH2 (1.5 eq),
4. TBAF, THF
3. Add ketone, 1 d
2. PMHS (5 eq)
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
93 (10 mol%), MeOH, rt, 12-14 h
PMHS, Sn(OTf)2 (10 mol%),
vitride (3%), MeC6H5, rt, 24 h
(R,R)-ebpe (20 mol%),
PMHS (1.1 eq), Et2Zn (2 mol%),
(98) 48% ee
(—) 81% ee
791
578
588
385
594
674
C9
O
S
O
O
O
Ketone
41 (0.4 mol%), THF, rt, 30 min
Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),
4. TBAF, THF
3. Add ketone, 1.6 d
2. PMHS (5 eq)
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
25 (1.1 mol%), –40°, THF, 3 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
126 (1 mol%), THF, –20°
Ph(1-Np)SiH2 (1.5 eq),
126 (1 mol%), THF, –20°
Ph(1-Np)SiH2 (1.5 eq),
93 (10 mol%), MeOH, rt
PMHS, Sn(OTf)2 (10 mol%),
126 (1 mol%), THF, –20°
Ph(1-Np)SiH2 (1.5 eq),
108 (1.2 mol%), 0°, 24 h
Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),
Conditions
O
I
OH
I (68) 92% ee
I (87) 87% ee
OH
S
O OH
OH
I (90) 95% ee
I
OH
(85) 50% ee
(90) 85% ee
(90) 92% ee
(77) 12% ee
(86) 87% ee
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
787
588
577
576
576
385
576
575
Refs.
675
C9-10
Ar
O
Ph
Ph
O
O
R Me Me i-Pr i-Pr i-Pr i-Pr i-Pr i-Pr
4-MeC6H4
4-MeC6H4
Ph
Ph
Ph
Ph
Ph
Ph
R
O
OH
Ar
O
N
Bu-n
O
O
CO2Me
6h 6h 4h
Et i-Pr Ph
n-BuOH
n-BuOH
i-PrOH
EtOH
MeOH
none
i-BuNH2
MeOH
Additive
7.0
3.8
5.5
5
5
—
4
4
x
32 h
14 h
5.5 h
6h
5h
39 h
4h
3h
Time
2. PMHS (6-10 eq), additive (x eq), rt
1. PhSiH3 (0.1 eq), 198 (0.2 eq), MeOH, 60°
NaOBu-t (1 mol%), THF/MeC6H5, –50°, 10 h
PMHS (4 eq), 124 (0.05 mol%), CuCl (1 mol%),
2. PMHS, ketone, MeOH (3-7 eq), 15°
pyrrolidine, MeOH, THF, 60°
1. PhSiH3 (0.1 eq), 198 (2 mol%),
Time
R
131 (2 mol%), MeC6H5, rt, 6 h
PMHS (1.2 eq), R2Zn (2 mol%),
92 (5 mol%), AgBF4 (2 mol%), THF, 0°, 1 d
Ph2SiH2 (1.3 eq), RhCl3 (1 mol%),
CO2Me
Ar
HO
Ph
Ph
48
(95)
(92)
(65)
(96)
(94)
(17)
(50)
(97)
R
OH
N O
Bu-n
99
—
—
99
99
90
—
97
% ee
OH
33
(31) OH
28
(>99)
% ee (>99)
O
OH
1S,2R 95% ee
I
OH + I + II (76), I:II = 54:46
CO2Me
(68) 83% ee
(50) 96% ee b
1S,2S 92% ee
II
OH
587
590
587
788
390
676
C10
C9-13
Ph
O
Me2C=CH(CH2)2
Ph
O
O
c-C6H11
Ph
BnO
i-Pr
Ph 10 h
8h
13 h
12 h
5h
Time
4. TBAF, THF
3. Add ketone, 0.8 d
2. PMHS (5 eq)
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
THF/TMEDA, 0°, 24 h
(MeO)3SiH (1 eq), Li2-histidine (10 mol%),
THF, –20°
Ph(1-Np)SiH2 (1.5 eq), 126 (1 mol%),
1
1
0.5
1
Et
x
Ph
R
2. PMHS, ketone, MeOH (3-7 eq), 15°
1
R
pyrrolidine, MeOH, THF, 60°
1. PhSiH3 (0.1 eq), 198 (x mol%),
Conditions
I
OH
OH
>98
99
98
98
98
% ee
R
I (88) 12% ee
Ph
O
(80)
(86)
(86)
(86)
(87)
BnO
Ar
OH
(91) 28% ee
(92) 46% ee
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
4-MeC6H4 Me
Ar
Ar
O
Ketone
588
593
576
587
Refs.
677
Ph
Ph
Ph
O
O
O
Pr-i
Pr-n
R
Pr-n I
OH
65 66 66
0° 20°
118 119
MeOH, rt, 12-14 h
PMHS, Sn(OTf)2 (10 mol%), 93 (10 mol%),
I (96) 44% ee
67
0°
117
Ligand
% ee
Pr-i
Pr-i
0°
I
OH
OH
116
Ph
Ph
Ph
OH
I (87) 97% ee
Ph
Ph
OH
Temp
ligand (0.5%), MeC6H5
Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),
4. TBAF, THF
3. Add ketone, 4.5 d
2. PMHS (5 eq)
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
1 (1.1 mol%), THF, –40°, 24 h
(3-FC6H4)2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),
MeC6H5, or THF, or MeC6H5/THF, –78°
PMHS (5 eq), CuCl, t-BuONa, 121 (0.005 mol%),
92, THF, –78°
Ph(1-Np)SiH2 (4 eq), [Rh(cod)Cl]2 (1 mol%),
1 (1.1 mol%), THF, –50°, 48 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),
(—)
(99)
88b
89
Cl
H
(79) 92% ee
R
% ee
R (93)
(70) 59% ee
(94) 81% ee
385
791
588
578
589
792
578
678
C10
MeO O
OMe O
Ketone
I
OH
II
43 (76) (89) (84)
2.4 4 10
MeC6H5 MeC6H5 MeC6H5
89
89
59
% ee (68)
x 2.4
THF
II
I (39) 93% ee
OH
I (80) 43% ee
I (70) 48% ee
MeO
(92) 99% ee
(89) 94% ee
Product(s) and Yield(s) (%)
(97) 92% ee
OMe OH
Solvent
44 (x mol%), solvent, 0°
Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (1 mol%),
Li-(R)-BINOL (10 mol%), 0°, 24 h
(MeO)3SiH (1 eq), Et2O/TMEDA (30:1),
(–)-44 (4 mol%), MeC6H5, rt
Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (1 mol%),
93 (10 mol%), MeOH, rt
PMHS, Sn(OTf)2 (10 mol%),
92, THF, –78°
Ph(1-Np)SiH2 (4 eq), [Rh(cod)Cl]2 (1 mol%),
MeC6H5, or THF, or MeC6H5/THF, –78°
PMHS (5 eq), CuCl, t-BuONa, 121 (0.005 mol%),
MeC6H5, or THF, or MeC6H5/THF, –78°
PMHS (5 eq), CuCl, t-BuONa, 121 (0.005 mol%),
Conditions
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
585
592
585
385
792
589
589
Refs.
679
C10
Ph
O OMe
2. PMHS, ketone, MeOH (3-7 eq), 15°
pyrrolidine, MeOH, THF
1. PhSiH3 (0.1 eq), 198 (2 mol%), MeOH, 60°,
(–)-34, THF, rt
MesPhSiH2, [Rh(cod)Cl]2 (2.5 mol%),
vitride (3%), MeC6H5, rt, 24 h
(R,R)-ebpe (20 mol%),
PMHS (1.1 eq), Et2Zn (2 mol%),
MeC6H5, 65°, 1 h
PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),
MeC6H5, 65°, 1 h
PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),
4. TBAF, THF
3. Add ketone, 1.6 d
2. PMHS (5 eq)
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
25 (1.1 mol%), –40°, THF, 4 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
126 (1 mol%), THF, –20°
Ph(1-Np)SiH2 (1.5 eq),
106 (1.2 mol%), 0°, 42 h
Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),
38 (0.5 mol%), Et2O, rt
Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (0.25 mol%),
AgBF4 (0.02 mol%), THF, 0°, 2 h
Ph2SiH2 (1.6 eq), 92 (4.0 mol%),
Ph
OH
I (95) 98% ee
I (—) 64% ee
I (94) 10% ee
OMe
II (94) 10% ee
I (92) 91% ee
I (83) 84% ee
I (90) 91% ee
I (70) 80% ee
II (95) 57% ee
I (92) 99% ee
(50) 98% ee b
587
586
594
783
783
588
577
576
575
571
580
680
C11
C10
Ph
Ph
Ph
N
O
O
O
S
Bu-t
C6H13-n
O
Ketone
–5° –5° 0°
116 117 119
1 (1.1 mol%), THF, –40°, 24 h
(3-FC6H4)2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),
4. TBAF, THF
3. Add ketone, 2.5 d
2. PMHS (5 eq)
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
Temp
Ligand
ligand (0.5%), MeC6H5
Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),
MeC6H5, 65°, 1 h
PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),
MeC6H5, 65°, 1 h
PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),
NaOBu-t (1 mol%), MeC6H5, –50°, 4h
PMHS (4 eq), 124 (0.05 mol %) CuCl (1 mol%),
Conditions
Ph
Ph
Bu-t
Bu-t
OH
OH
86
86
84
(97) 90% ee
(90) 89% eeb
(96) 95% ee
(10) 5% ee
(9) 5% ee
C6H13-n
OH
% ee
OH
I
OH
I (—)
Ph
Ph
N
S
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
578
588
791
783
783
590
Refs.
681
Ph
O
Ph
O
O
O
C6H13-n
CO2Me
1 3 3
1 3 3
123 121 123
4. TBAF, THF
3. Add ketone, 1 d
2. PhSiH3 (1.5 eq)
—
–50° 77
(88) 82% ee
(—)
—
–78°
OH
81
(—)
12 h 70
% ee (98)
Time
OH
C6H13-n
CO2Me
–50°
Ph
O
Ph
OH
Temp
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
y
Ligand x
NaOBu-t (y mol%), MeC6H5
PMHS (4 eq), ligand (0.05 mol%), CuCl (x mol%),
MeC6H5, rt, 18 h
PMHS (1.2 eq), Et2Zn (2 mol%), 131 (2 mol%),
(0)
588
590
788
682
C12
C11
O
O
N
O
O O
C6H13-n
Ketone
126 (1 mol%), THF, –20°
Ph(1-Np)SiH2 (1.5 eq),
DIOP (1.1 mol%), THF, rt, 48 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),
MeC6H5, 65°, 1 h
(R) or (S)-195-2n-BuLi (5 mol%),
PhSiH3 (1.1 eq),
126 (1 mol%), THF, –20°
[Rh(cod)]SbF6 (1 mol%),
Ph(1-Np)SiH2 (1.5 eq),
87 (10 mol%), MeOH, rt
PMHS, Sn(OTf)2 (10 mol%),
THF/TMEDA, 0°, 24 h
(MeO)3SiH (1 eq), Li2-histidine (10 mol%),
123 (0.05 mol%), MeC6H5, –50°, 10 h
PMHS (4 eq), CuCl/NaOBu-t (1 mol%),
Conditions
I
HO
HO
HO
N OH
O
I (98) >99% ee
HO
HO
C6H13-n
(92) 91% ee
(0)
(90) 98% ee
(5) 33% ee
(66) 30% ee
(68) 83% ee
Product(s) and Yield(s) (%)
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
576
606
783
576
385
593
590
Refs.
683
1-Np
1-Np
Ph
O
BnO
O
O
O
O
Ph
Br
CO2Et
O
Ph
OH
OH
I
I:II 80.5:19.5 82.5:17.5 79:21 92:8 90:10 93.5:6.5
(60) (56) (84) (95) (92)
110 112 113 114 115
II
(82)
1-Np I + II
+
HO
Ph
(64) 84% ee R
(98) 44% ee
II 1S,2S 96% ee
OH
(70) 70% ee
(—) 75% ee
109
I
+
CO2Et
Br
I (94) 28% ee
1-Np
HO
1-Np
Ph
OH
I 1S,2R 99% ee
OH
BnO
O
Catalyst
0-20°, 10-15 h
Ph2SiH2 (1.2 eq), C6H6, catalyst (0.01 eq),
MeC6H5, 65°, 3 h
PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),
MeC6H5, rt, 24 h
(S,S)-ebpe (20 mol%), vitride (3%),
PMHS (1.1 eq), Et2Zn (20 mol%),
(EtO)3SiH, THF, 198, 96 h
MeOH, rt, 12-14 h
PMHS, Sn(OTf)2 (10 mol%), 87 (10 mol%),
87 (5 mol%), AgBF4 (2 mol%), THF, 0°, 1 d
Ph2SiH2 (1.3 eq), RhCl3 (1 mol%),
126 (1 mol%), THF, –20°
[Rh(cod)]SbF6 (1 mol%),
Ph(1-Np)SiH2 (1.5 eq),
I + II (92), I:II = 51:49
804
783
594
794
385
390
576
684
C13
C12
Ph
O
2-Np
1-Np
O
O
Ketone
61
20°
109
4. TBAF, THF
3. Add ketone, 2.5 d
2. PhSiH3 (1.5 eq)
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
C6H5Me, 65°, 1 h
PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),
C6H5Me, 65°, 1 h
PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),
4. TBAF, THF
3. Add ketone, 3 d
2. PMHS (5 eq)
1. 197 (4.5 eq), 2 n-BuLi, C6H6
MeC6H5, rt, 24 h
(R,R)-ebpe (20 mol%), vitride (3%), I
Ph
II OH
2-Np
OH
Product(s) and Yield(s) (%)
(88) 82% ee
(100) 25% ee
(—) 80% ee
(—)
I (100) 62% ee
I (84) 95% ee
2-Np
OH
42
20°
119 84
29
0°
20° 113 PMHS (1.1 eq), Et2Zn (20 mol%),
% ee
Temp
116
1-Np
HO
Ligand
ligand (0.5%), MeC6H5
Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),
Conditions
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
588
783
783
588
594
791
Refs.
685
C16
C14-20
R2
Et Me i-Bu Bn
Ph
BnCH2
Ph
Ph
O
Me
4-ClC6H4
R1
R2
O
O
R1
BnO
O
68:32 75:25
(21) (27)
CONHNp-1 CONHNp-1
38 (0.5 mol%), Et2O, rt
Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (0.25 mol%),
54:46
(76)
CONHNp-1
OH
61:39
(47)
CONHPh
R:S 64:36
R1
OH
OH
(87)
R
R2
BnO
O
CONHPh
3
0° to rt, 24 h
R3 N Cl3SiH (1.5 eq), CHO (0.1 eq), CH2Cl2,
126 (1 mol%), THF, –20°
Ph(1-Np)SiH2 (1.5 eq),
(100) 90% ee
(80) >99% ee
571
379
576
686
C22
H
O
HO
I:II 67:33 64:36
Catalyst Rh-(+)-DIOP Rh-(–)-DIOP
I (—)
H
H
7:3
Rh-(–)-DIOP
Ph2SiH2, catalyst, C6H6, 22°
7:3
Rh-(+)-DIOP
H
H
10 mol% of the catalyst was employed.
20 mol% of the catalyst was employed.
An additional 5 mol% of BINOL was added.
10 mol% of cinchonidine was added.
1-Naphthylphenylsilane was used as the reducing silane.
e
f
g
h
c
d
The configuration of the product was not determined.
The reducing agent was (EtO)3SiH.
b
OH
H
H
HO
+
H II (—)
H
II (—)
H
OH
H +
H
OH
I:II
I (—)
H
Product(s) and Yield(s) (%)
Catalyst
Ph2SiH2, catalyst, C6H6, 22°
The catalyst is S,S-[1,2-bis(tetrahydroindenyl)ethane]titanium (IV) and derivatives.
H
H
H
O
Conditions
TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)
a
O
H
Ketone
OH
573
573
Refs.
687
C6-12
C6
rt 50° rt rt rt
2.0 1.2 1.4 2.0 3.0
CH2Cl2/MeC6H5 CH2Cl2 CH2Cl2/MeC6H5 CH2Cl2/MeC6H5 CH2Cl2/MeC6H5
Me
BnCH2
BnCH2
BnCH2
BnCH2 O
(62) (52) (52) (42) (67) (64) (65)
BnBr BrCH2CO2Et 1-bromo-3-methyl-2-butene n-BuI BnBr allyl bromide MeI
Me
Me
Me
BnCH2
BnCH2
BnCH2
BnCH2
1
I + II
R
(69) O
(67)
(64)
(60)
(62)
(53)
R2 X
rt, 24 h
2. R2X, TBAT (1.2 eq), CH2Cl2/MeC6H5 (1:1),
(S)-p-Tol-BINAP, MeC6H5, 0°, 2-3 h
R (62)
O
O
R1
R
1
rt
2.0
Me
1. Ph2SiH2 (0.53 eq), CuCl (5%), NaOBu-t (5%),
rt
2.0
CH2Cl2 THF
Me
Temp
x
Solvent-2
R
2. BnBr (x eq), TBAT (1.2 eq), temp
(S)-p-Tol-BINAP, MeC6H5, 0°, 2-3 h
1. Ph2SiH2 (0.53 eq), CuCl (5%), NaOBu-t (5%),
–78°, 24 h
t-BuONa (5 mol%) (S)-p-Tol-BINAP (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
Conditions
I
+
73:27
76:24
94:6
85:15
80:20
94:6
92:8
I:II
R2
Bn
O
(42) 94% ee
R
1
II
R2
Product(s) and Yield(s) (%)
TABLE 31. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES
R
O
O
Enone
459
459
595
Refs.
688
C8
C7
C6
O
O
O
Enone
DIOP (1.1 mol%), THF, rt, 10 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),
3. Add ketone, 3 d
2. PMHS (10 eq)
1. 197 (4.5 eq), n-BuLi (9 eq), C6H6
126 (1 mol%), THF, –20°
[Rh(cod)]SbF6 (1 mol%),
Ph(1-Np)SiH2 (1.5 eq),
25 (1.1 mol%), –40°, THF, 4 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
124 (0.1-0.5 mol%), MeC6H5, 0°, 4.5 h
PMHS (2 eq), (Ph3P)CuH (1 mol%),
–78°, 24 h
t-BuONa (5 mol%), (S)-BIPHEMP (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
(R)-38 (0.5 mol%), Et2O, 0°, 15 h
Ph2SiH2 (1.5 eq), [Ir(cod)Cl]2 (0.25 mol%),
Conditions
I
OH
I (71) 95% ee
I (70) 85% ee
(71) 95% ee
(96) 90% ee
(61) 92% ee
(100) 84% eea
I (85) 91% ee
O
O
OH
Product(s) and Yield(s) (%)
TABLE 31. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued)
606
588
576
577
597
595
582
Refs.
689
C9
O
O
O
Bu-n
O
CO2Me
O
95 98
dioxane/THF
0°, 12 h
t-BuONa (5 mol%), (S)-p-Tol-BINAP (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
0°, 24 h
t-BuONa (5 mol%), (S)-p-Tol-BINAP (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
124 (0.1-0.5 mol%), MeC6H5, –78°, 18 h
PMHS (2 eq), (Ph3P)CuH (1 mol%),
92
THF
O
O
O
90
MeC6H5
Bu-n
% ee
I I (>90)
O
CH2Cl2
124 (0.1-0.5 mol%), 0°, 6 h Solvent
PMHS (1 eq), (Ph3P)CuH (1 mol%),
124 (0.00036 mol%), MeC6H5, –35°, 3 d
PMHS (2 eq), (Ph3P)CuH (1 mol%),
(S)-p-Tol-BINAP (5 mol%), 0°, 3 d
t-BuONa (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
(86) 92% ee
(84) 98% ee
CO2Me
CO2Me
(94) 97% ee
(88) 98.5% ee
(88) 94% ee
595
595
597
597
597
595
690
C11
C10
O
Ph
O
O
O
Bu-n
C5H11-n
Enone
15°, 24 h
t-BuONa (5 mol%), (S)-BINAP (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
THF/TMEDA, 0°, 24 h
(MeO)3SiH (1 eq), Li2-histidine (10 mol%),
THF/TMEDA, 0°, 24 h
(MeO)3SiH (1 eq), Li2-histidine (10 mol%),
Li-(R)-BINOL (10 mol%), 0°, 24 h
(MeO)3SiH (1 eq), Et2O/TMEDA (30:1),
–78°, 2 d
t-BuONa (5 mol%), (S)-p-Tol-BINAP (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
25 (1.1 mol%), THF, –40°, 4 h
Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),
2. PMHS, ketone, MeOH (3-7 eq), 15°, 4 h
pyrrolidine, MeOH, THF, 60°
1. PhSiH3 (0.1 eq), 198 (2 mol%),
Conditions
O
Ph
Ph
Ph
O
OH
OH
OH
OH
OH
Bu-n
C5H11-n
C5H11-n
(87) 96% ee
(78) 70% ee
(91) 28% ee
(91) 57% ee
(82) 87% ee
(84) 87% ee
(90) 84% ee
Product(s) and Yield(s) (%)
TABLE 31. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued)
595
593
593
592
595
597
587
Refs.
691
C13
C12
O
O
O
O
O
Bn O
vitride (3%), MeC6H5, rt, 24 h
(R,R)-ebpe (20 mol%),
PMHS (1.1 eq), Et2Zn (20 mol%),
(S)-p-Tol-BINAP (5 mol%), 0°, 24 h
t-BuONa (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
then TBAF
(S)-p-Tol-BINAP (10 mol%), MeC6H5;
PMHS (1.1 eq), CuCl/NaOBu-t,
124 (0.1-0.5 mol%), MeC6H5, 0°, 6 h
PMHS (2 eq), (Ph3P)CuH (1 mol%),
+
O
Bn OH
Ph
(—)
(—) 18% ee
(86) 94% ee
O
(90) 96% ee
(92) 97.3% ee
(97) 97.5% ee
(78) 96% ee
Ph 45% conv., 71.6% ee
O
Bn
C7H13-n
O
O
Bn
Bn
124 (0.1-0.5 mol%), MeC6H5, –78°, 36 h
PMHS (2 eq), (Ph3P)CuH (1 mol%),
124 (0.4 mol%), MeC6H5, –78°
NaOMe (0.5 mol%),
PMHS (2 eq), CuCl (1 mol%),
O
O
O
Ph
C7H13-n
Bn
(S)-p-Tol-BINAP (5 mol%), 0°, 24 h
t-BuONa (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
+
O
Ph
(—)
594
595
596
597
597
597
595
692
C14-19
R2
R2 BnCH2 BnCH2 BnCH2 BnCH2 i-Pr Ph
R1
Me
i-Pr
t-Bu
t-BuO2CCH2
Bn
Me
R I + II (89) (94) (94) (91) (95) (90)
–50° –30° 0° –50° –50° –50°
I Temp
MeC6H5, temp, 26 h; then TBAF
t-BuONa (1.7 eq), t-BuOH (5.0 eq),
96.5:3.5
91.5:8.5
90:10
93.5:6.5
93:7
91:9
I:II
+
56.0
–50°
CH2CO2Bu-t
2
50.7
0°
t-Bu
R1
53.2
–78°
n-Bu
PMHS (2.2 eq), CuCl/(S)-p-Tol-BINAP (10 mol%),
56.5
0°
O
55.6
–78°
i-Pr
Ph
R
Me
O
I
+
% Conv. I
R1
R
O
91
93
93
94
93
91
% ee I
II
O
95.3
91.0
90.6
97.4
94.6
% ee
O
R2
Ph
(—)
R +
Product(s) and Yield(s) (%)
Temp
Ph
MeC6H5, temp; then TBAF
(S)-p-Tol-BINAP (10 mol%),
PMHS (1.1 eq), CuCl/NaOBu-t,
Conditions
TABLE 31. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued)
R
R1
R
O
Enone O
Ph
(—)
596
596
Refs.
693
C16
C15
a
O
O
Bn
Pr-i
Ph
OBn
The product is the (–) enantiomer.
O
Bn
O
124 (0.1-0.5 mol%), MeC6H5, –35°, 16 h
PMHS (2 eq), (Ph3P)CuH (1 mol%),
0°, 24 h
t-BuONa (5 mol%), (S)-p-Tol-BINAP (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
(S)-BINAP (5 mol%), –78°, 4 d
t-BuONa (5 mol%),
PMHS (1.05 eq), CuCl (5 mol%),
MeC6H5; then TBAF
(S)-p-Tol-BINAP (10 mol%),
PMHS (1.1 eq), CuCl/NaOBu-t, +
Bn
O
O
O
Bn
O
Ph
(91) 94% ee
(95) 99.5% ee
OBn
+ (—) Pr-i
(82) 96% ee
Pr-i 56% conv., 95.6% ee
Bn
O Bn
O
Pr-i
(—)
597
595
595
596
694
C4
O
+
+
OMe Ph
PMBO
BnO
+
Ester
O
O
O
H
H
H
90 98 98 98
[Ir(cod)Cl]2 [Ir(cod)Cl]2 [Ir(coe)2Cl]2 Ir(cod)BF4
2. H3O+
98 (7.5 mol%), rt, 24 h
1. Et2MeSiH, [Ir(cod)Cl]2 (2.5 mol%),
2. H3O+
98 (7.5 mol %), rt, 24 h
1. Et2MeSiH, [Ir(cod)Cl]2 (2.5 mol%),
98
88
[Ir(cod)Cl]2
[Rh(cod)Cl]2
87
[Ir(cod)Cl]2
98
86
[Ir(cod)Cl]2
(CO)2Ir(acac)
Ligand
Catalyst
2. H3O+
ligand (7.5 mol%), CH2Cl2, rt, 24 h
1.Et2MeSiH , catalyst (5 mol%),
Conditions
PMBO
BnO
Ph
OH
I
O
86
4.0:1
OMe
10
94
4.4:1 82
92
3.9:1
2.0:1
70
1.5:1
4.0:1
0 80
2.0:1
II
O
BnO
50
1:1.3
+
% ee I
I:II
Ph
OH
OH
OMe
I
OMe
+ PMBO
OH
I + II (76), I:II = 6:1, er I > 95:5
O
I III I + II (59), I:II = 9.5:1, er I = 98:2 OH
OH
(9)
(56)
(35)
(53)
(48)
(30)
(32)
(46)
( 95:5, (I + II):III + IV > 95:5 OH
+
OBn
OH
601
601
601
696
C5
C4-9
C4
OEt 2. H3O+
Ph
O OEt
OMe
+
Ph
OH
2R,3R
—
2R,3R
O OEt
34
38
88
—
—
2R,3S
Conf. syn % ee anti Conf. anti
I II I + II (68), I:II = 6.6:1, 94% ee I
OH
87
3.4:1 (72)
Ph
98 (7.5 mol%), CH2Cl2, rt, 45 h
58
O
II
O
+ anti diastereomer
syn:anti % ee syn
OR
1.4:1
H
Ph
(21)
1. Et2MeSiH, [Ir(coe)2Cl]2 (5 mol%),
2. H3O+
t-Bu
O
H
(R)-BINAP (6.5 mol%), CH2Cl2, rt, 24 h
—
82
—
96
96
96
91
Ph
Ph
—
(0)
(E)-PhCH=CH
O
2.7:1
(65)
BnOCH2CH2
OH
—
(99
48
7
34
% ee anti
+ anti diastereomer
(90) syn:anti = 3:1, 75% ee syn
(54) syn:anti = 6:1, 71% ee syn
(86) syn:anti = 6:1, 83% ee syn
Product(s) and Yield(s) (%)
% ee syn
OPh
3.4:1
Et2MeSiH (1.75 eq),
R
O
OH
OH
OH
syn:anti
(R)-BINAP (6.5 mol%), CH2Cl2, rt, 24 h
[Rh(cod)Cl]2 (2.5 mol%),
O
O
OH
PhO
PhO
PhO
O
Ph
H
Et2MeSiH (1.2 eq),
{Rh(cod)[(R)-BINAP)]}BF4 (5 mol%), rt, 12 h
Et2MeSiH (1.75 eq),
rt, 12 h
{Rh(cod)[(R)-BINAP)]}BF4 (5 mol%),
Et2MeSiH (1.75 eq),
rt, 12 h
{Rh(cod)[(R)-BINAP)]}BF4 (5 mol%),
Et2MeSiH (1.75 eq),
R
O
O
O
O
Conditions
TABLE 32. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued) Ester
470
470
603
470
470
470
Refs.
699
C11
O
O
n-Bu
O
O
Bn
O OEt
OPh
Ph
O +
O H
4h 3h
–40°
CuCl2•2H2O MeC6H5/C5H12/i-PrOH –20°
PMHS
THF/C5H12/EtOH
CuCl
5 min
rt
PMHS
24 h
–15°
C6H12/EtOH
48 h
CuCl
Time rt
(90)
(90)
(89)
(34)
(50)
(80) 95% ee
Temp
OEt
PMHS
MeC6H5
Additive
Bn
O
Ph
92
93
—
91
80
% ee
(52) syn:anti = 3.9:1, 88% ee syn
(96) 99% ee
DEE/C5H12
CuCl
PMHS
O
O
n-Bu
O
O
PhO
OH
Ph2SiH2 CuCl
Cu Salt
Silane
(S)-p-Tol-BINAP (5 mol%)
NaOBu-t (5-20 mol%), additive,
Silane (4 eq), Cu salt (5 mol%),
MeC6H5, 0°
124 (7.3 mol%), t-BuOH (1.13 eq),
PMHS (2 eq), (Ph3P)CuH (7.3 mol%),
124 (0.1 mol%), t-BuOH (1.1 eq), rt, 1 h
PMHS (2 eq), (Ph3P)CuH (0.5 mol%),
(S)-BINAP (6.5 mol%), rt, 48 h
Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),
O
599
598
598
470
700
C12
C11
Ph
O
O
O
CO2Et
CO2Et
OPh
+
O H
MeC6H5, rt, 24 h
(S)-p-Tol-BINAP (10 mol%),
NaOBu-t (5 mol %),
PMHS (4 eq) CuCl (5 mol%),
MeC6H5, 0°
124 (7.3 mol%), t-BuOH (1.13 eq),
PMHS (2 eq), (Ph3P)CuH (7.3 mol%),
MeC6H5, 0°
124 (7.3 mol%), t-BuOH (1.13 eq),
PMHS (2 eq), (Ph3P)CuH (7.3 mol%),
(S)-p-Tol-BINAP (0.1 mol%), C6H12, rt
NaOBu-t (0.2 mol%), t-AmOH,
PMHS (4 eq), CuCl2 (0.1 mol%),
t-BuOH, rt, 1 h
PMHS, CuH, 124 (0.2-0.4 mol%),
(S)-BINAP (6.5 mol%), rt, 48 h
Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),
Conditions
O
I
CO2Et
CO2Et
OH
I (84) 90% ee
I (94) 91% ee
I (92) 98% ee
Ph
O
PhO
O
(95) 86% ee
(91) 98% ee
(0)
Product(s) and Yield(s) (%)
TABLE 32. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued) Ester
600
598
598
599
598
470
Refs.
701
C14
C13
Ph
Ph
R
O
OEt
OEt
OEt
O
O
+
O
O
OPh
OEt
O H
t-BuOH, 0°, 1 h
PMHS, CuH, 124 (0.2-0.4 mol%),
MeC6H5, 0°
124 (7.3 mol%), t-BuOH (1.13 eq),
PMHS (2 eq), (Ph3P)CuH (7.3 mol%),
(S)-BINAP (6.5 mol%), rt, 48 h
Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),
MeC6H5, rt, 25 h
(S)-p-Tol-BINAP (10 mol%),
NaOBu-t (5 mol%),
PMHS (4 eq), CuCl (5 mol%),
t-BuOH, 0°, 1 h
PMHS, CuH, 124 (0.2-0.4 mol%),
MeC6H5, rt
(S)-p-Tol-BINAP (10 mol%),
NaOBu-t (5 mol%),
PMHS (4 eq) CuCl (5 mol%),
MeC6H5, rt, 25 h
(S)-p-Tol-BINAP (10 mol%),
NaOBu-t (5 mol%),
PMHS (4 eq) CuCl (5 mol%),
Ph
PhO
Ph
R
O
Ph
O
Ph
O
OEt
OH
OEt
OEt
OEt
OEt O
O
O 22 h
24 h
Time
(97) 99% ee
(97) 99% ee
92
81
% ee
— % ee syn
(30) syn:anti = 4.4:1,
(89)
(94)
(90) 85% ee
(90) 95% ee
c-C6H11
n-C6H13
R
OEt
(98) 91% ee
O
598
598
470
600
598
600
600
702
C15
C14
Ph
Ph
Ph
Ph
O
O
OEt
OEt
OEt
O
OEt
O
t-BuOH, rt, 1 h
PMHS, CuH, 124 (0.2-0.4 mol%),
t-BuOH, rt, 1 h
PMHS, CuH, 124 (0.2-0.4 mol%),
MeC6H5, rt, 18 h
(S)-p-Tol-BINAP (10 mol%),
NaOBu-t (5 mol%),
PMHS (4 eq), CuCl (5 mol%),
MeC6H5, rt, 20 h
(S)-p-Tol-BINAP (10 mol%),
NaOBu-t (5 mol%),
PMHS (4 eq), CuCl (5 mol%),
MeC6H5, 0°
124 (7.3 mol%), t-BuOH (1.13 eq),
PMHS (2 eq), (Ph3P)CuH (7.3 mol%),
MeC6H5, 0°
124 (7.3 mol%), t-BuOH (1.13 eq),
PMHS (2 eq), (Ph3P)CuH (7.3 mol%),
t-BuOH, 0°, 1 h
PMHS, CuH, 124 (0.2-0.4 mol%),
Conditions
II
I O
O
Ph
Ph
I (96) 83% ee
II (95) 84% ee
II (98) 99% ee
Ph
Ph
O
O
OEt
OEt
OEt
OEt
(94) 98% ee
(93) 99% ee
(96) 90% ee
(98) 99% ee
Product(s) and Yield(s) (%)
TABLE 32. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued) Ester
598
598
600
600
598
598
598
Refs.
703
C15-18
R R
(49)
PhO
Ph(CH2)3
(S)-BINAP (6.5 mol%), rt, 48 h
[Rh(cod)Cl]2 (5 mol%),
3.9:1
3.8:1
4.2:1
syn:anti
OH
(53)
H
O
TBSO(CH2)3
+
Et2MeSiH (5 eq),
(54)
OPh
O
n-C6H13
R
O
93
88
88
% ee syn
470
704
C18
C15
C12
PMPN
PMPN
PMPN
PMPN
O
O
O
O
Bu-n
Pr-n
Lactam
F
C6H5F, air, rt, 3 h
t-AmOH (16 eq), (R)-p-Tol-BINAP (0.5 mol%),
NaOBu-t (5 mol%),
PMHS (16 eq), CuCl2•2 H2O (2.5 mol%),
MeC6H5/C5H12, 0°, 3 h
t-AmOH, (S)-p-Tol-BINAP (20 mol%),
PMHS (4 eq), CuCl2•2 H2O (5 mol%), NaOBu-t (20 mol%),
MeC6H5/C5H12, 0°, 3 h
t-AmOH, (S)-p-Tol-BINAP (20 mol%),
PMHS (4 eq), CuCl2•2 H2O (5 mol%), NaOBu-t (20 mol%),
MeC6H5/C5H12, rt, 1 h
t-AmOH, (S)-p-Tol-BINAP (5 mol%),
PMHS (4 eq), CuCl2•2 H2O (0.1 mol%), NaOBu-t (20 mol%),
Conditions
PMPN
PMPN
PMPN
PMPN
O
O
O
O
Bu-n
Pr-n
F
(89) 90% ee
(94) 94% ee
(89) 91% ee
(90) 92% ee
Product(s) and Yield(s) (%)
TABLE 33. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED LACTAMS
599
599
599
599
Refs.
705
C9
C8
Ph
N
N
Me
Pr-n
Imine
Et2O, 0°, 48 h
[Ir(cod)Cl]2 (10 mol%),
Ph2SiH2 (2 eq), 38 (10 mol%),
Et2O, 0°, 60 h
[Ir(cod)Cl]2 (10 mol%),
Ph2SiH2 (2 eq), 38 (10 mol%),
MeC6H5, 0°, 90 h
[(Ph3P)RuCl2]2 (10 mol%),
Ph2SiH2 (2 eq), 38 (10 mol%),
I (24) 16% ee
I (56) 89% ee
I (51) 73% ee
605
605
605
610
35°, 12 h
610
I (94) 97% ee I (95) 99% ee
PhSiH3 (4.5 eq), 198 (1 mol%), rt, 12 h
612
PhSiH3 (4.5 eq), 198 (0.02 mol%),
(100) 97% ee
611
611
612
I
(82) 99% ee
(80) 99% ee
Refs.
I (50) —% ee
Ph
Pr-n
Pr-n
NHMe
Boc
N
Boc
N
Product(s) and Yield(s) (%)
PMHS (10 eq), 198 (10 mol%), rt, 48 h
PhSiH3 (4 eq), 198 (1 mol%), rt, 12 h
2. (t-BuO2C)2O
MeOH (0.1 eq), THF, rt, 6 h
pyrrolidine (0.1 eq),
1. PhSiH3 (2 eq), S,S-198 (1 mol%),
2. (t-BuO2C)2O
MeOH (0.1 eq), THF, rt, 6 h
pyrrolidine (0.1 eq),
1. PhSiH3 (2 eq), R,R-198 (1 mol%),
Conditions
TABLE 34. ASYMMETRIC ORGANOSILANE REDUCTION OF IMINES
706
C10
C9
O
Ph
R
N
O
N
Me
N
N
N
Imine
H2 (80 psig), 45°, 23 h
PhSiH3 (2.5-3 eq), 198,
H2 (80 psig), 50°, 23 h
PhSiH3 (2.5-3 eq), 198,
H2 (80 psig), 65°, 16 h
PhSiH3 (2.5-3 eq), 198,
H2 (80 psig), 65°, 7 h
PhSiH3 (2.5-3 eq), 198,
198 (0.1 mol%), 35°, 12 h
PhSiH3 (4.5 eq),
35°, 12 h
PhSiH3 (4.5 eq), 198 (x mol%),
Conditions
O
Ph
Ph
R
O
N H
N H
NHMe
x 0.1
N H
N H
N H
(86) 99% ee
98
92
% ee
(72) 99% ee
(79) 99% ee
(82) 99% ee
(87)
0.02 (96)
(96) 98% ee
4-ClC6H4
c-C6H11
R
Product(s) and Yield(s) (%)
TABLE 34. ASYMMETRIC ORGANOSILANE REDUCTION OF IMINES (Continued)
613
613
613
613
610
610
Refs.
707
N
Ph
Time 20 h 60 h 20 h 50 h 50 h 30 h 30 h 40 h
Ligand 37 37 37 35 36 38 38 41
Metal Complex [Ir(cod)Cl]2 [Ir(cod)Cl]2 [Rh(cod)Cl]2 [Ir(cod)Cl]2 [Ir(cod)Cl]2 [Ir(cod)Cl]2 [Rh(cod)Cl]2 [Ir(cod)Cl]2
ligand (5 mol%), Et2O, 0°
metal complex (10 mol%),
(>95)
(17)
(>95)
trace
(78)
(75)
(>95)
(>95)
86
32
71
—
88
34
88
85
% ee
34
20 h
[Rh(cod)Cl]2
I
85
(75)
20 h
[Ir(cod)Cl]2
Ph2SiH2 (2 eq),
88
(>95)
40 h
% ee (60)
Time
I
Ph
(Ph3P)RuCl2
N H
Metal Complex
MeC6H5, 0°
metal complex (10 mol%),
Ph2SiH2 (2 eq), 38 (10 mol%),
605
605
708
C11
C10-13
2.24
3,4-(MeO)2C6H3 a
Ph
N
Ph
N
Me
0-20°
0-20° 72 h
20 h
H2 (500 psig), 65°, 24 h
PhSiH3 (2.5-3 eq), 198,
Et2O, 0°, 100 h
[Ir(cod)Cl]2 (10 mol%),
Ph2SiH2 (2 eq), 38 (10 mol%),
MeC6H5, 0°, 50 h
(Ph3P)RuCl2 (10 mol%),
Ph2SiH2 (2 eq), 38 (10 mol%),
PhSiH3 (4.5 eq), 198 (1 mol%), rt, 12 h
PhSiH3 (4.5 eq), 198 (1 mol%), rt, 12 h
2.0
2.24
3,4-(MeO)2C6H3
3,4,5-(MeO)3C6H2 Me N
2.0
2-MeOC6H4 48 h
2.0
4-BrC6H4 a 0-20°
30 h
0-20°
2.2
Ph 48 h
69 h
0°
2.2
Ph
0-20°
32 h
0-20°
2.6
Ph
24 h
32 h
0-20°
2.2
Ph
0-20°
Time
Temp
2. (CF3CO)2O x
N
(–)-DIOP (x mol%)
1. Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (2 mol%),
Conditions
N H
CF3
I
O
Ph
I (78) 98% ee
31
33
33
31
60
64
61
59
59
(80) 96% ee
(91) 97% ee
(81)
(89)
(87)
(85)
(82)
(84)
(84)
(83)
(85)
H
Ar
% ee
+
(10) 25% ee
NHMe
NHMe
N
I (18) 7% ee
Ph
H
Ar
R
S
R
R
R
R
R
R
R
Conf.
N CF3
O
Product(s) and Yield(s) (%)
TABLE 34. ASYMMETRIC ORGANOSILANE REDUCTION OF IMINES (Continued)
Ar
Ar
Imine
613
605
605
610
610
606
Refs.
709
C12
Ph
MeO
MeO
Cl
HO
N
7
N N
N
E:Z = 20:1
E:Z = 15:1
Pr-n
H2 (80 psig), 65°, 30 h
PhSiH3 (2.5-3 eq), 198,
65°, 50 h
PhSiH3 (2.5-3 eq), 198, H2 (80 psig),
(+)-DIOP, C6H6, 1°
Ph2SiH2 (2 eq), [Rh(C2H4)2]2 (2 mol%),
i-BuNH2 (1.5 eq), 65°, 2.5 h
PhSiH3 (9 eq), 198 (0.05 mol%),
s-BuNH2 (1.5 eq), 65°, 2.5 h
PhSiH3 (9 eq), 198 (2 mol%),
i-BuNH2 (1.5 eq), 65°, 2.5 h
PMHS (9 eq), 198 (0.5 mol%),
H2 (500 psig), 65°, 8 h
PhSiH3 (1.1 eq), 198, 7
HN
N H
Ph
N
I (79) 9% ee
MeO
MeO
I
I (95) 98% ee
I (73) 93% ee
Cl
HO
I
(93) 5.7% ee
(95) 98% ee
(74) 97% ee
NH
Pr-n
(84) 99% ee
613
613
607
612
612
612
613
710
C13
C12-18
R1
N
N
N
R
2
(46) (43) (69) (50)
CHCl3 CHCl3 CH2Cl2 CHCl3
Bn Ph Ph Ph
Ph 4-CF3C6H4 2-C10H7 2-C10H7
PMP
4
TMS
3. i-BuNH2, slow addition, 60°
2. Add imine
1. PMHS, 198
H2 (80 psig), 50°, 27 h
4
87
80
87
8
22
85
80
76
