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Fieserand Fieser's
Reagentsfor OrganicSynthesis VOLUME SEVENTEEN
Mary Fieser Harv...
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i ha;rI, L .^-t' . t .. . . ' | ' r
Fieserand Fieser's
Reagentsfor OrganicSynthesis VOLUME SEVENTEEN
Mary Fieser Harvard University
PUBLICAIION A WILEY-INTERSCIENCE John Wiley & Sons, Inc. NEW YORK / CHICHESTER / BRISBANE / TORONTO / SINGAPORE
,i}-
\.
' ( ) I v li
I
ADVISORS JEFF ROHDE
MARK BIL,ODEAU
STRUCTURE COMPOSITION TIMOTHY GRINSTgweR
MIHer Azrrutoene MeRr Russerr MencaRsr Hsu
Ttu JeursoN Tee Bun SHIN Onr-euoo ScHRRBn SspBsRSaRsHe,n
PROOFREADERS MlcHRnL H. KRESS
RBssccaM. MensH RrcHenoM. GoonveN
ALEXANDER R. MucI DAVID H. RIPIN BRYAN E. R0BERTS
JAY F. LARRow
Dnsoneu EvReno
Susan L. VeNnsRvsr-op, DEBORAH T, HuNc
KARLENE A. CIMPRICH
PI ltl r{l d
F d
It
paper' This text is printed on acid-free & Sons' Inc' Copyright O 1994 by John Wiley s i m u l t a n c o u s l yi n C a n a d a A l l r i g h t s r e s e r v e t lP u b l i s h c d any part of this work beyond Reproductionor translationof r08 of the 1e76 United or r07 ;v Section ;;i';;i;;;. permissionofrhe. copyright Siut". Copyrigni Act without the or further permission for Requests owner is untu*ful to thc PermissionsDepartment' inforrnution should be addressed NY Third Avenue' New York' John Wiley & Sons, lnc', 605 I 0 15 8 - 0 0 1 2 . in Publication Data: Lihrary of Cong,ressCataloging ISBN 0-471-00074-4 ISSN 0271-616X of America Printcd in rhe United Stares 1
0
98
1
6
5
4
3
2
l
PREFACE This volume of Reagentsincludes material published in late 1990 to early 1993.As usual,this volume hasreceivedtremendoushelp from Harvardgraduate students.Mark Bilodeau and Jeff Rohde have read and correctedlarge portions of the manuscript.Other advisers have provided invaluable correction of the page proofs. Another group, for the first time, was responsiblefor composition of the chemical formulas in ChemDraw. MARY FIESER C ambridge, M assachusetts June 1994
CONTENTS
Reagents 1 Author Index 409 Subject Index 425
Acylsilanes. Review. Cirillo and Panekr have reviewed progress in the chemistry of these compounds during the last two to three years (48 references).A new synthesis involves (l)2 to form homologationof aldehydeswith methoxybis(trimethylsilyl)methyllithium enol ethersof an acylsilane(equationI). Acylsilanes can be preparedin high yield by
?rr'
(l) Liclsi(cH3)312 Tl|'n. H'
/ocHs
H.o,
?
'si1cH.;. 5t-e2'l" RCH2/ -si1cH.;.
1
o
(rr) *Asr, (ilr)
o
CuCN
+ Atlsi(cH3)313 T H F
83-98%
e, CH3CN/ H2O ---;*"-
*A.,("rr), O
*Ar,("r.).
1X3,,"r.,.
reactionof S-2-pyridyl esterswith aluminum tris(trimethylsilane)and CuCN (1 equiv.), equationII.3 A third general synthesis of acylsilanes involves anodic oxidation of 2-alkyl-2-trimethylsilyl-1,3-dithianes (equationIII)4. Acyldimethylphenylsilanesundergohighly selectivehydrogenation(Pd/C) to aldehydes without effect on benzyl or BOM ether groups, acetonides,or r-butyldimethylsilyl groups (equationIV).
(CHe)e 'l - -o Mo M
(tU CoHs-Si-'.\,CH3 i l l
o
H2,Pd lc c2HsoH
osi(cH3)3
75o/"
OMOM I H\.,r\,\..CH3
i l l o osi(cH3)3
Acylsilanesundergohighly diastereoselective reactionswith RLi and RMgX to afford s_r'n-adducts, particularly when the chiral center is substitutedby a phenyl group.5
Alanine
gt.
CHq
t -J.- -Si(CH3)3
coHs- lf o
bULI 92"/o
9t. . c"n,ft;Btrr.E',T.,4>;;
Cra" |1^'
> 100:1
asx j euor.r-r CHq
C.H.
t cuHrlY"
cl
OH
Acylsilanesarereducedtoa-alkoxysilanesbyavarietyofmetalhydrides.Reductionwith provides(R)-alcoholsin >80% ee and in 30-65Vo (-)-chlorodiisopinocamphenylborane yield.6
L-rl
su fbr ,
rrkl O
It -S|(CH3)3
(CH3)zCH-
C) - tpe2BOl
rnr,zo"60%
9H
rs
s:ndr!
"\si(cH3)3 (cH3)2cH H,98o/o ee
e rP. F. Cirillo and J. S. Panek,Or8' Prep' Proc' Intl'' 24' 553 (1992)' (1991)' 2J. Yoshida,S. Matsunaga,y. Iiicni, f' Makawa' and S' Isoe' J' org'' 56' 1307 4929 (1991'). 3 M. Nakada, S. Nakamura, s. rJuyu.r,i, and M. Ohno, TetrahedronLetters, 32, a K. Suda, J. Watanabe,and T. Takanami,ibid'' 33' 1355 (1992)' s P. F. Cirillo and J. S. Panek, ibid', 32' 45'7 (1'991)' 3l' 46'77 6J.A. Soderquist,c.L. Anderson,'E.I. Miranda, and I. Rivera, TetrahedronLetters' S' Modi' D' Williams' and Khasnis' D' Lamb' G'W' Strickland' B' (1990); J.D. Breynak, J H. Zhang,J. Org'' 56,7076 (1991)'
Alanine, CH3CH(NH2)COOH' a.Methyta-aminoacids.lTheseaminoacidsareofgenera|interestbecausesuch substituentsinpeptidescanrestricttherotationalfreedomofamidebonds'andhence A general synthesis is an extension of the secondary and tertiary structures of proteins' acids' but involves alkylation of the Seebach'smethod tbr a-methylation of a-amino the schiff baseformed from this o-amino a_methyl a_amino acid o_ or i-alanine. Thus acidandbenzaldehydeiscyclizedbybenzylchloroformatetothe(2S,4R)-oxazolidinone l.Theenolateof|'isalkylatedbyvariouselectrophilesfromthefaceoppositetothatof can be hydrolyzedby brief treatment the phenyl group. The products,such as (2S'4S)-2' derivativeof the a-methyl a-amino with LioH or NaoH in cH3oH/H2O to a protected
i \ h
t-rb Sl r-lr Ll j.rn
p-Alanine
1) C6H5CHO
.Bu ,OH
CH3, ,,H
;H2N-g-CooNa
2)ctcooBzl
305"/"
1) LDA 2) BTCH2CO2C(CH3)3
P-(o cuHu""
(*4.cHt n cbl
76"/."
(2S,4R)-1
P-
(coHs)zcHz 79o/o
?ut' coHui cHsAcHs 8"/"
reduction Reductive deoxygenation of alkyl aryl ketones is best effected in two steps: addition by increased be yield can The AlBrr. with i-BuzAlH followed by treatmentwith of Cp2TiCl2 in the second steP.
)Hs 1) i- BuAIH 2) AlBr3,Cp2TiCl2
C6H5COCH3
75"/o
sequential Reductive deoxygenation of dialkyl ketones is best effected in three steps: catalyst. Ni(acac)2 a and iBu2AlH finally and AlBr3, with i-BuzAlH, treatment
AlkYlaluminum halides
1)i-Bu2AlH
O
I
nonenes
sri-au2,Lil:rN:i(acacr'n - nonane
-Bu
(32o/ol
(48y.\
CH3(CHjal
Thesereactionscanbeusedforreductionofthecorrespondingsecondarya|coholsto primary alcohols ol p:enols' alkanes, but do not reduce an alkynylmagnesium brocomplexes'a Reaction of Cyclization of oWnyiu{inium midewithdichlorobis(cyclopentadienyl)titanium'resultsinaTicomplexlinessentially and to water than is more stable to air oxidation quantitative yield' This ""rnpttl< these complexes with an alkylaluminum halide' the Grignard reagent' On i"utrntnt to a 4-' attached alkene to an exocyclic trisubstituted (n: l_3)undergo "y"rjut^i* (2)' 5-. or 6-memberedring
R
R
'l'
'l' 'l'
?'
*(cHr)i
o"l)#3iJB[."t'i'*(cHr);'t'"'"0' 5O - 79o/o
1 ,n = 1 - 3 n = 1 - 3 1) RAlCl2or R2AlCl -30' -'-78" 2) HOAo'H2O 72 '93"/o
sol+ ,*" L""r,.". 2,n=1-3
'syn-insertionto thus 3 undergoesintramolecular This cyclization is regioselective; product' give 4 as the exclusivecyclic
9 9 o / od e 97o/oAE
t s-
I D. Enders,H. J. Scherer,and G. Raabe,Angew' Chem' Int' Ed' 3O' 1664 (1991)' Aniline
r h
and Nitrobenzene.
Addition and 4-nilrodiphenylamine't . of animixture to a 2Hzos (cH3)4NoH to tetramethylammonium hydroxide dihydrate, Direct coupling
to 4-nitrosodiphenylamine
lineandnitrobenzeneresu|tsinaa-complexl,whichisthenconvertedtoamixture (3)' The ratio of 2 and 3 of 4-nitrosodiphenylamine (2) and 4-nitrodiphenylamine
oH
C6H5NH.
-. o-
C6H5NH2 + C6H5NO2
Cur,r,U"-$*O 2
I I
c6H5NO2
tol
cuHuxH$uo, 3
ratio of nitrobenzeneis increased' dependson the ratio of aniline and nitrobenzene.As the act as an intermolecularoxidizing the yield of 3 is increased.Evidently nitrobenzenecan agent of I to give 3. I M. K. Stern,F. D. Hileman,and J. K. Bashkin,Am' Soc'' ll4' 923'1(1992)'
:-t
Lr ;.r / Lr! i c
{
2-Arenesulfonyl-3-aryloxazirdin€s
)cH3
Antimony(V) chloride- Silver hexafluoroantimonate. This combinationgeneratesSbCU . SbF; (l). Beckmann rearrangemenL The antimony(V) salt I is an effective catalyst for Beckmannrearrangementof ketoxime trimethylsilyl ethersto amidesor lactams.l
lilosi(cH3)3 1 , C H 3 C NA,
\
C6H5NHCOCH3
cH,
c.Hu
/n3
t7
/
V
-----------> 77"/o
NOSi(CH3)3
l3 S-
rlc
t": ee
Pinacol rearrangement.2 This reaction is generally effected with at least one equiv. of conc.HzSOr. It can alsobe effectedwith the salt (l), preparedfrom SbCls and AgSbFr, in high yield under mild conditions.In addition only 20 molVaof I is required.
o i l n
1,CH2C|2 15-20"
rdJrnon (' l a n l -
av
ml\turc .rnd 3
OH
Hzo
{.\o2
-_Noz
Nrc.lscd,
)\rJizing
o
| 9sHs
c6H5-l\-c6H5 CnH" - - oI H
99
lcuHuy.cAcuHu
lT. Mukaiyama and T. Harada,Chem. Letters, 1653 (1991). 2lbid, idem, sl (1992).
2-Arenesulfonyl-3-aryloxaziridines,ll, 108; 12, 392-393; 13, 23-24; 14,22. Oxidative desulfunylation; d-diketones.t The potassium enolate of an d-sulfonyl ketoneon oxidationwith a typical oxaziridineof this type, 2-[(p-chlorophenyl)sulfonyl]3-(p-chlorophenyl)oxaziridine(1), is converted into an a-diketone in 78-85Vo yield. Use of lithium or sodium basesresultsin poor yields. Addition of HMPA or l8-crown6 can be beneficial.The procedureis applicableto cyclic and acyclic systemsand is compatiblewith olefins, even allenic groups.
Arene(tricarbonyl)chromium
complexes
t
o Ar-tLtX
H'
'sorAr
r il.1 :-l{r
1, Ar = 4-ClCoHa
I1r
o
TS T(
So2ror llfl#Fl|;
t-.4
81v"
i-Pr
'i-Pr
i-Pr
i_pr
I D.R. Williams, J. org.,57,3740(1992). G.S.Amato,andM.Y. Osterhout, L.A. Robinson, Arene(tricarbonyl)chromium complexes. Nucleophilic substitution.t carbon nucleophiles react with the cr(co)3 complex or of indane followed by oxidative decomplexation(iodine) to effect highly selective exclusive substitution a to the ring junction. Similar but less pronouncedselectivity Good but obtains in reactionsof the Cr(CO)3 complex of 1,2,3,4-tetrahydronaphthalene.
CN
(cH3)2c-cN 1) Lic(cH3)2cN 2) lz 90%
ra\1 \/
..NS.-1 | ll
) \--N HN
1 0 0 :1
R = CH(CHg)z
83o/"
> 1 0 0 :1
R = CHg
91To
1 5 :1
r S . H . K a n g , T . S . H w a n g , W . J . K i m , a n d J . K . L i m , T e t r a h e d r o n L e t t e r s , 3 24' 0 1 5 ( 1 9 9 1 ) '
* ith LiOH I >iX)n ricld
under 3 atm r*\ used to d or onll proi
J E. Baldru .\-(Beonld
N-(Benzyldimethylsilyl)methyl-2-(+)-methoxymethyl)pyrmlidine
le- .,ll (E)-squalene
-\ Yanagtsawa,
t-. . F:
27
Benzylchlorobis(triphenylphosphine) palladium(II). Stille macrocyclization. Several macrocylic antibiotics contain a y-oxo-a,Bunsaturatedestergroup. Macrolidesof this type can be obtainedby Stille intramolecular coupling.r The substratesare availablefrom Mitsunobu esterificationof propriolic acid with an crr-hydroxyester followed by hydrostannylationto give B-stannyl alkenoates1 as a L:1 mixture of (Z)- and (E)-isomers.Selectivesaponificationof the methyl ester R I
R o ll r{ -o- '\I
P(c6H5)3, -c_,. . , r _ o . . c rDEAD .
Hol\1cHr)ecH2coocH3
"H-COOH vvv'7/'
-1cHr)ecH2coocH3
H. lorr tll.l The reacrrr-r Jlh\ lsilyl triflate
t
Bu3SnH B(C2H5)3
o
I
Bu3Sny'v-O
lcf
s oTf t t -
(( - anOmef
F
lCHr;nCH2COOCH3 >eo"/o
R
Pd(il),co i l l /^o tcHz)ro100" i ll
Jr
cocl
Bu3Sn9 2 3
I
')(cog!fl:
'l(ZJE=1:1)
O
-
1)LioH
R
2
R=H
53"/"
R = CH.-
7Oo/"
O (E)-3
'. r\. l10l (1992).
r"' . ,.ilr I ethers of s. 1.5-disubstituted F . ,"\ rrcncrallylow
with LiOH provides the free acid which is convertedinto the acid chloride to give 2 in >9OVo yield. Intramolecularcoupling of 2 to form 3 is effected with a Pd(II) catalyst under 3 atms. of carbon monoxide at high dilution in toluenc. This cross coupling can be usedto obtain 12- to 20-memberedrings. Dimeric macrolidesare formed as the main or only products in the case of shorter precursors. I J.E. Baldwin,R.M. Adlington,andS.H. Ramcharitar, J. C.S. Chem.Comm.'94O(1991)-
,C
--R
N-(Benzyldimethylsilyl)methyl-2-(+ )-methoxymethyl)pyrrolidine.
l-
s :':.s
"rr).iT c6H5cH2 |
cH3o\,/() -r: : l5 (1991).
(S)-(+)-1
28
l,l/-Bi-2,2/'naphthol-Dichlorodiisopmpoxytitanium The anion (sec-Buli) of (S)-1 reacts with
Asymmetric synthesisof l,3-diols't
ethyleneoxidetogiveasingleproduct2.oxidativecleavageoftheC-Sibondgivesthe r,:-oiot(S>(_)-3in>ggToee.Similarreactionoftheanionoflwith/-butyloxirane which are separable by or L,2-epoxyhexane gives a mixture of two diastereomers' chromatographyandconvertedtosyn-andanti-|,3-diolsonoxidativecleavage.In the 1,3-diols have the (1S)these reactionsas in the reaction with aliphatic epoxides, configuration.
1) sec-BuLi
(S)-(+)-1
2 ) o ,/\ --r**
: CHs)Si._ CHs I
KF,H2O2 65"/"
,N.
cH3o__{_jr
C6H5--1.^---,OH : 6H (S)-t)-3 (>99o/.ee)
2
C6H5.-.-,.^-...-.Bu{ CHs-Si1)sec-BuLi ')A c1o,.1. cH;'-l (S)-(+)-1
,*
6ff
,N. rH3o__97Vo 1,4-regioselectivity.Attempts to polymerize phenylenesdirectly results in mixtures of para-, meta-, and ortho-linkedoligomers. In contrastpolymerizationof cls2 with I in CcHsCI results in exclusive 5,6-bis(trimethylsilyloxy)-1,3-cyclohexadiene 3. This polymer is convertedinto poly(pformation of the 1,4-poly-1,3-cyclohexadiene phenylene)(5) by conversionof the trimethylsilyloxy groups to acetyl groups followed by pyrolysis.
"o
1,
c6Hscl
.Jor-\J,t,,r. 3
(cH3)3sior-\ si(cH3)3
(cHs)
2
-..,.CHs
({})
93o/"
tI
1)F 2) CH3OH
{ ( \l:Pd and :( )\ R. group" r . . 1 . l i v ct h a n
(o)
+
1) Ac2O,Py 2) , -CHSCOOH
)J1;^ 4
I D. L. Gin. V. P. Conticello, and R. H. Grubbs,Am. Soc., 114,316'7 (1992).
32
Bis(1,5-cyclooctadiene)nickel-Tbiphenylphosphine
Bis(cyclooctadiene)nickel. Phenol synthesis. In the presenceof this Ni(O) catalystcyclobutenonescan couple with internal alkynesto form phenolsin 50-80% yield. Two phenolsare obtainedfrom unsymmetricalalkynes with only slight regioselectivitybased on the size of the alkyl substituents.Modest selectivity obtains with oxygen-substitutedalkynes.
R1
--/o
ill
I
.lll
CHz
f
I
CoHs
cH3ooc\ I (t)
R1
R2
0" Ni(coD)2,
products (endol diene substitue
R2
R1 C5H5
R2 75Yo
R1, R2 = CzHs R1 = CHg, R2 = (CH2)2OTHP
65:35
47o/o
cHgooc
This phenolsynthesisdiffers from the thermalreactionof cyclobutenoneswith alkynes (15, 160) in that activated alkynes are not required and the ultimate positions of the alkyne substituentsin the phenol are different.
(il) cHr:91
1M.A. HuffmanandL.S. Liebeskind, Am. Soc.,ll3' 21'71(1991)' Bis(1,5-cyclooctadiene)nickel(0)-Chlorotrialkylsilane,Ni(COD)2-ClSiR3' Conjugateadditionofalkenyltributylstannanestoa,B-enals.Thereactioncan Ni(COD)z be effected with a chlorotrialkylsilane(1 equiv.) and a catalytic amount of evidently reaction The yield.l in 48-79Vo (E)-silyl ether enol in an in DMF and results involves a 1-silyloxyallylnickel(Il) intermediate(a)'
CHr:611"tO
+
CHr:611tntr.
+
,liene with pha The preser orvnorbornadk rdduct (equalx
",|l(l),.
+ ClSiR3
(ilr)
4*.OSiR3
I CtNiT ' 2
a
-;**
z
f''\'OSiR3
("r,
EIZ=>SO:'|
rB.A. Grisso, Am.Soc',l14, 5160(1992)' andP.B. Mackenzie, J.R. Johnson,
These prclu on the regiosc tnho- and fru \t. l:utens ar
-Ttiphenylphosphine' Bis(1,5-cyclooctadiene)nickel In the presenceof [2 + 2 + 2] Homo-Diels-Alder reactions of norbornadiene,t alkenesat 80' with activated react can Ni(coD), and P(c6H5)3 (1:2) norbornadienes indicate that regioselectivity the of studies to give 12 + 2 + 2] adducts.Preliminary Thus molecules' of complex for synthesis this homo-Diels-Atder reactioncan be useful two in only results acrylonitrile with reaction of methyl norbornadiene-2--carboxylate
Bis(cyclopcrtr p-Kcto ct heramethl'ldis Jre convertd
Bis(cyclopentadienyl)chloro(hydrido)zirconium
C.1na()Uple :r:e,l from rt :hc alkYl
R1 t^
products (endof exo : 2.3:I), in which the electron-withdrawing groups are para to the diene substituent (equation I). Only two products are formed from reaction of the same
^
\
Ni(coD)2 cH3ooc. rl\
"Jgi'li,E u,"^"oo">> €
i
33
cnr:Lncrtr
6Hroocy\
Ua"*
'cN
exo-para
enoo-para Rz
2.3:1
:r."".&..r."".&
N cH3ooc\l\ r r:h .rlkvnes t r , . n .o f t h e
(tt)
SO2C6H5 C6H5S02
cHr:cHsircuHu
exo-para
exo-meta 2 : 1
t.r!li()n
can
,( \itCOD)z or: cr idently
diene with phenyl vinyl sulfone, the exo-para and exo-metaisomersin a ratio of 2:1. The presenceof a methoxy group on the diene lowers the reactivity, but 2-methoxynorbornadienecan react with methyl vinyl ketone to provide a single endo'ortho adduct (equationIII).
(ilr)
o$o"'"
+
CHr:\ po ci.
,.l\ ( YocHs 51v" *oo"r, endo-ottho
These preliminary resultsindicate that substituentgroups can exert a marked effect on the regioselectivityof this homo-Diels-Alder reactionwith a generalpreferencefor ortho- and para-isomers. I M. Lautensand L.G. Edwards, J. Org., 56,3761(1991). c lrc\cnce of l\cnc: at 80' r : r J r c a t et h a t rlriulcs. Thus , lr ()nly two
Bis(cyclopentadienyl)chloro(hydrido)zirconium,CpzZrHCl. B-Keto esters - enoales.l The enolates of B-keto esters, prepared with lithium in DME, on reactionwith the Schwartzreagent(1 equiv.) at0-2O' hexamethyldisilazane are converted into enoatesin 55-70% yield.
2,2i-Bis(diphenylphosphino)-1,1/binaphthyl
o.
.co2cH3
X
groups of the PhosPhin useful percursorto thc ,
DME 1) LiNlsi(cH3)312, 2\ Cp2Z(HQl
o
o
i l l l cH3l^focx, I -ruHcoq
o A -"or=,
CoHsNCo2Et
2
CoHs-
rA.G.GodfreyandBGanem'TetrahedronLefters'33"746'l(1992) 1'' Bis(2,6-diphenytphenoxide)tris(4-methylbenzyl)niobium(V)' aryloxide is an effiniobium This arenes'2 i)y'u't'a' All-cis Hydrogrr"tu,'tj cientcatalystforregioselectiu"t'yo,og.nutionofpolynucleararenes.Thusphenanthrene isreducedtotheg,l0-dihydrodcrivativeandanoctahydrophcnanthrenc'Anthraccneis H z ,1 C6H12,80oC
(78/o)
(22o/")
H
Z\,'\' I
l l
\-\2
|
' l
f^ff
l l \''-'/'\l
2-alkylidenecYcloPen
o
) H
(95.5%)
Asymmetric hYdroT tion can be effectc'd I regardlessof the gcom
(4.5o/o\
rH NMR spcctra indicates that Analysis of thc convertedto an octahydro derivativc' thchydrogcnatomsareallintroducedonthesamcfaceinthccascofnaphthalene' anthracene,and acenaPhthcnc' 10' 321 Rothwcll'Organometallics' f R.W. Chcsnut, G.G. Jacob,J'S' Yu' P'E' Fanwick'l'P Am Srtc''rr4'1s2'7(tssz)' an997o ee by use of Rh[(S)- or (R)-BINAP]CIOa as catalyst'
9€
Rh[(s)-BTNAP]Cl04
cHo \
QH2CI2,20'
rcHz
\ 3 /
1"
R 2, R = t-Bu
o tl
87o/o
R = C(CHs)zCHzCHg 84% R=Bu
9Oo/o
3, S, >99% ee S, >99% ee S , 9 1 %e e
enantioselective B-Amino acids.T A useful route to chiral B-amino acids involves such as 1. Thus hydrogenationof (E)-1 hydrogenationof methyl B-(acylamino)acrylates
38
ll,4-Bis{diplc
(R)-or(S)-2,2r-Bis(diphenylphosphino)l,l/-binaphthvl
catafyzedby a complex of Ru(OCOCHT)zwith (R)-BINAP furnishes(S)-2 in 960/oee. Surprisingly (Z)-1 is convertedunder the same conditions to (R)-2 in 5Vo ee. Hydro-
CH3..\..NHCOCH3
H2 Ru(ll)-(R)-BINAP
cH..-fruHcoor.
o H &
(r)
I
tl cH3ooc'-
1,4-Bis(diphenylphosg Diastereoselectirc I diols.' This catalvstis alcohols (12, 426- 121 and vinylsilaneshavinc
cH3ooc'-
( E ) -1
I
c*t'',M
(S) - 2, 96% ee
oH cr flr) genation of either (E)- or (Z)-l catalyzedby Rh+(CH3OH)2CIO4 complexcd with (R)-BINAP resultsin (R)-2 but with modest enantioselectivity(45-6lqa cc). optically Asymmetric carbonylation of alkenyl hatides; a-methylene lactones.' active a-methylene lactoncscan bc preparcdby carbonylationof alkenyl halides such o/o)in the presenceof thallium acctate. as I catalyzedby PdCl2-(R)-BINAP (5 mol
CHz
cH3Fl r
P d c r 2 - ( R )- B I N A P TlOAc,CH3CN
+
Ho-100:1) 2
flt) with
nrli\.d
CeHrr
?' ?'. ,/'-z'\sic6H5(cH3;
sic6H5(cH3)2 ?" c.Hrr'l\-AcH.
Hz,1
syn(>500:1) '
t )pticallY
I
I l.,li.lcs such
oo-"
ln' :!ctatc.
{-- / /. p t
I KBr, HOOAc
J
OH OH -\'z-,^ -CHs
CeHtt-
\
Honc r.raoRc,
syn - dlol
2^' to
I M. Lautens, Angew.Chem.Int. Ed., 31,232 (1992). C.-H. Zhang,andC. M. Crudden,
;=' ""
(\r .t\\'mmetfic hs.ttinq (R)- or nr:r
A suitable
1., 1,. prcpared i . . 1 l . r l v s t sg i v e s
II,4-Bis(diphenylphosphino)butanelnorbornadienerhodium trifluoromethanesulfonate, l(14, 44-45). Diastereoselectivehydrogenation of vinyl sulfones and sulfoxides.r Hydrogenation of the vinyl sulfone 2 with the Rh catalyst I proceeds in 99Vo de to give 3. Similar hydrogenationof the correspondingsulfoxide provides 5, which on perborate oxidation gives the threo-isomerof 3. Apparently the steric course of hydrogen-
9H,
lrrt' r
I
L:\.'
fdrahedron
0H anti -3,9910 de
2
.. Rhl'tt', Rh.1
pHr cuHu-s\cH.
o ) : - 1 h . r( 1 9 9 1 )
cuHusor&cH.
c6H5so2\cH3 OH
I s h i z a k i ,S .
t|,.
CH.
Rh.1H , 2,25"
(R,R)- 4
o
H
CHs oxidation cuHusor\cH.
CHr cunu-s\icH.
o
o
syn - 5,99o/ode
H
o svn - 3
H
40
Bis(dipivaloylmethanato)nickel(Il)
o
ation of sulfones is controlled by the hydroxy group, whereas the configuration at sulfuf controls the course of hydrogenation of sulfoxides.
)-''."'
I D. Ando,C. Bevan,J.M. Brown,andD.W. Price,J.C.S. Chem'Comm',592(1992)'
(,
""ol-
(TRAP)' 2,2//-Bis[1-(diphenylphosphino)ethyl]-1,1//-biferrocene
\Z^\
I rT. Yamada, K. Takah.
(s,s)-(R,R)-TRAP
( l ee1).
[N,M-Bis(4-methoxl
CHtt"'1"tt P(C6Hs)2 A catalyst prepared from RhH(co)[P(c6Hs)r]: Asymmetric Michael adilition.t ketones and TRAP can effect asymmetric addition of a-cyano carboxylatesto vinyl selectivity' or acrolein. Note that isopropyl estersshow the highest
O
NC.--.-COO-iPr
l l ^ , r + J CHs"'-\y'w'1z
CHs
3-5"
o ),,--,-,-coo-t-Pr CHs cf;\N R (B4oloee)
o ^)--,,o"^r*
Ncrcoo-i-Pr CHs
o 11A.--'-*Coo-i-Pr cH]'ctl R (84oloee)
Expoxidation ol t epoxidation with oxr'1 reductantis 2-meth1'l alkenes.
cr
cH.A
I M. Sawamura, andY. Ito, Am. Soc-,ll4' 8295('1992)' H. Hamashima, Bis(dipivaloylmethanato)nickel(ID, Ni(dpm)r. 1,3Baeyer-Villiger ox'dation.t Complexes of nickel coordinated with several aldehyde an and oxygen molecular with diketones are effective catalysts for oxidations involving or alcohol reductant(16,30-32). Such oxygenationsare much saferthan those oxygenation catalyzed a such peracid. a peroxide or the usual oxidantssuch as hydrogen can be used for Baeyer_ Yilliger oxidation of either cyclic or acyclic ketones.Highest yields are obtained with bis(dipivaloylmethanato)nickel(Il)as catalyst (l mol%) and isovaleraldehyde as reductant.
cl
' T . T a k a i ,E . H a t a , K. Y
1,2-Bis(methylene)c B,y-Enones. Rr siumprovidesa magn
1,2-Bis(methylene)cycloalkane-Magnesium
o
)ri .r: \ulfur
t
93%
l
\-.-
L)""
02, RCHO,Ni(dpm)2 ctcH2cH2ct,25"
/-'-a"'"
)
"r,o.]-
cH3oY\
-"Y
4l
CHs
o
\o\o4.,.
76%
o IT. Yamada, K. Takahashi,K. Kato, T. Takai, S. Inoki, and T. Mukaiyama, Chem. Letters, 647 (1991). I),
lN,M-Bis(4-methoxysalicylidene)-o-phenylenediaminelcobaltfl
cH3o
9CHs
; { t '(r, H s ) r ] r in\ I kctones (1)
a
COO-i-Pr
\ ^ . ,I\
Expoxidation of alkenes.t In the presence of this complex, alkenes undergo epoxidation with oxygen (oxidant) and cyclic ketones as reductant.The most useful Yields are -8OVo for trisubstitutedor exo-terminal reductantis 2-methylcyclohexanone.
\-
,r
alkenes.
COO-l-Pr
t *
1.' O,.- r-{/
CH. t cH./\--czHrs
n .lcral
1,3-
ri .'n aldehYde h,'.c involving rJ,,rrgenation 1,'xg. Highest 11 nrol%) and
"r.t).
1ao
/ \
g
\__J
/cH.\ n -v
CHa t -
cn^4-y'c'Htu -o-
#rs u*- sn.Alc,H,,
rT. Takai,E. Hata,K. Yorozu,andT. Mukaiyama, (7992). Chem.Letters,2O77 1,2-Bis(methylene)cycloalkane-Magnesium,16, 198. with activated magneB,y-Enones. Reaction of 1,2-bis(methylene)cyclohexane sium providesa magnesiumcomplex (1). This complex reactswith ethyl acetateat - 10'
42
Bis(oxazolines)
when heated to form a spiro enol containing a cyclopropane ring (a). This intermediate undergoes ring expansion and protonation to form 2'
cHz
+i..t;
r->--f I ll ,Ms
cH3cooEt
-78'-
Enantio*l t S)-phenr'lglr rs a highlv cn * ith -j-acn lor'
-10"
\-,ry
CHz
6Hs)1 ' CHs-
1
2)H3o' a>r-\ .."-ZcH" -oH I | -oMsoEt (-L-A"t' '''' ** Wcr, 2
(r) cHz
Ms/- o4",
oJ
,r-( E:E
1 Diels-Alder cycloadditions.r This pyrone undergoes Diels-Alder reactions at l-5-100" to form adducts that on radical debromination afford halogen-freebicyclic lactones.It is thereforea practical equivalentto 2-pyrone itself.
SrR3 ,co2cH3
' ir \cH.
")) o'?t*
+cH,:6116es,k
P" :e
":Y-cooH #---/ (endolexo = 100:0)
,1""r:""""o o".r^l -''"1
2) NaBH4, cH3oH,25'
rh l'it:, ctherate(1-3 *..; * ith the Burgess r Jihrdration could rl'rrnc Predominates' ! lr,16 n carbocation
ttv
csA,cH3oH
">-\tr>-cH2oH--ffi* #--_/
Br:-Z\..COOCH3
I I----,'-\CH2oH
HO-
K. Afarinkra and G. H. Posner, TetrahedronLetters, 33,7839 (1992).
(5S,6R)-4-r-Butoxycarbonyl-5,6-dipenyl-2,3,5,6'tetrahydm-4II'1,4-oxazin-2-one
54
(5S,6R)-4-t-Butoxycarbonyl-5,6-dipenyl-2,3,5,6'tetrahydro-4H'1,4'oxazin-2'one) 14, 58-59. Asymmetric synthesisof arylglycines.r These glycines are difficult to obtain in optically pure form becausethey readily undergo base-catalyzedracemization.One of the most useful routes involves the Williams glycinate (l). Bromination followed by alkylation with an arylcupfateor an afene (ZnCl2 catalysis)provides 2. Removal of the Boc group (ISiR3),hydrolysisof the lactonering, and oxidative removal of benzaldehyde provides the free amino acid. Even a furanylglycine can be prepared(equationII). 1)lsi(cH3)3
QoHs
QoHs
coHs,. aHs,,, o l]l:?";'"'o ,,"_*-cooH r.,---n f | | 111"1i".""r," -
tr ) aocN\,,\
s6%
nu
eocN-*.-\
*
o
H-"\cuH,
,i\ur,
QoHs caHs,,,.a/\o
2)(o) , zncr,
HzN H2tpd
c6Hs,,. (-o
ao"il-.,.,,\o ,{
trans- ( - ) -2-t-Buty.k1
u)-?
I
90o/"€€
This oxazinoneroute can be usedto obtain bisaryl glycines by a version of the Stille coupling rcaction (equationlll).
goHs
t'3ttli-,,o.,".
CoHs
cuH'\Ao 31il?''"*"cuHu:A. I
( I r r ,
|
BocN:o,\O
|
R. M. Williams and J
CoHs
1)NBS
(rr) eo"rl_ (o--=t-
B2%ee
zv"/o
I
I
This chiral alcoh chloroacetate(reaoio ltvcr acetonepowder :hcn be saponifiedto This alcohol w.ha r\\'mmetric induction icss effective than ti1
BocN---,,\O
s\ B ' H
P. Esser,H. Buschm ,1992\.
\
/
Tfo
r-Butyldimethylsily-l r Intramolecular .1 r rth NEtt can effec r'lvcyclic systemfuv
l-,ot
t-Butyldimethylsilyl
trifluomrnethanesulfonate
l.{ 99:1)
o H o t t l
o H o
cH3->") "\_,
Butyllithium Diastereosela cthers(l) with Br selectivity,depex hv Petersonelim t rienes.
(CH3)35i-.tzz
(syn/anti= 99:1) Double kinetic resolution.
Davies et al.2 have noted that the enantiomeric selectiv-
ityofSharplessasymmetricepoxidationofanallylicalcoholcanbeenhancedinsome of the allylic alcohol I with casesby use of two kinetic resolutions.Thus epoxidation the epoxide2 and the less (+)-DiPT as the chiral component(58% conversion)provides
*t.-Z>
(cH3)3s
reactiveenantiomer(R)ofl,whichcanberecoveredandepoxidizedwith(-)-DiPT. I in 86% ee. This strategy is Using this technique,the epoxide 3 was obtained from
a
R=H
OH
I
l r l CHs 1
t-BuOOH, Ti(o-iP04, (+) - DiPT , 410/o
R=CHs R = CzHs
CHe
CHs ( R ) -1
eel 2 (5Oo/o t-BuOOH, I Ti(O-iP04, | 59"/. (-) DiPr I
Thus the ethcr product is reducs Jicne5. Acidic cli .clcctivity. In coo 1 7 )w i t h h i g h s e
I
OH
I
f
N^
l v " \,/,,,cHs 3 (86% ee)
on|yusefulwhentheracematesofthea|lylicalcoholdonotdiffersignificantly are available' reactivity and when both optical forms of the chiral reagent Letters'32' 2687(199-l)' I M. Bailey, I. E. Mark
CH2=611611r)2OTBS
] [cp2zncr(cH2)4orBs
o ,,\ (/
tcH'
f-V.. l l t
)
\Z^-tri
tazr 3
o
, CuBr.S(CH3)2
CH2:N-(C2H5)2\ 85'
\
G,.r2)4orBS
\
I
,^
fit'
1) Cp2zr(H)Cl 2\ , CuBr S(CHg)z ( FO
-
tl
o
0-o
v
with various active enop
I J.H. Tidwell,D. R. Senn (Z)-Vinylstannes.2 (Z)-Mnylstannanes can be prepared by hydrozirconation of followed by proton quench. stannylacetylenes
B-Chlorobis(iso-2-ethg I Preparation:
1 ) C p z Z r ( H ) CTl ,H F
CH3:SnBu3
\-at'{
2\ H2O. +
92"/"
CHs
SnBu3
\- I
cH3"-'\c t P. Wipf andJ.H. Smitrovich, J. Org., 56, 6494(1991,). 2 B. H. Lipschutz,R. Keil, andJ.C. Bafion,Tetrahedron Letters,33,5861(1992).
Chlorobis(cyclopentadienyl)methylzirconium,Cp2Zr(Cl)CH3,15, 81 Indole synthesis.t A novel route to 4-iodoindoles involves reaction of N-allyl-Nbenzyl-2-bromoaniline(1) with this zirconoceneto form the zirconacycle2, which is converted into 3 by iodination and elimination. This product undergoesene reactions
Asymrnetric reduai campheylborane(lpclB( ketones:they show link alkyl groups are similar i 1l). Thus acetylcyclohe rcduced in 95Voee (6-5
B-Chlombis(iso-2-ethylapinocampheyl)borane
Br .i
:.rincS followed bY addition
OCHz I
f-BuLi Cp2Zr(CH3)Cl
N,. I Bzl
[r :',r.rration of alkYl cuprates
CpzZt,-7
-CH+
/95% de
o C H q-
1,rHF
I
(lr)
--;*
Tlo-"utu 1...t"
cuHu
coHs
lcHi2cH=cH2
Chem'' f f' l8-18^(1972)' r M.R. Churchill, S.A' Bezman, and J'A' osborn' J Inorg' ll4, 5466 (1992)' soc., Am. 2 J. Aub6, X. peng, v. w-g, ""J F. Takusagawa'
(R)-1 can also be convertedtnto ester of (S)-alanine(2) to form th CycloProPanation.t Chromiu gt with unactivated l,3-dienes as vinylcycloProPaneswith high rcg result in a alkylmethoxYcarbenes
occurs selectivelywith the least I with 1,3-dienesthat can adoPt thc Chromium aminocarbenes pentacarThe chromium amino-carbene I' Asymmetric synethesisof tlipeptides't (methyl)carbene]chromium(0)' bonyl [(R-1-az a-2,2-dimelhyl-:-*u-S-pf'"nylcyclopentyl) with amino esters under coupling carbonylative derived from (R)-alanin", und"'go"t (S'S)-dipeptideswith high diastereoselectivity' irradiation (visible lighQ at 0' tolorm
*
cn/6cru,
"^r,
l$o(Co)5
erAocH.
o
CoHs / p
\
(co)scr\ ni;b tcH. cil. cHl (R)-1
H t l * cHog'\o(cHe).
C O ,h v , 0 " THF
H
88V"
I NHz
F- /
B"{'z\c,',
(s)-2
O
CHs
ocH3
cH.JAru\o,"'.t.,. cuHul4N-*-Bn. -cHa \.
o_J
b
i
(R,S,S)-3(s8:2)
Cr(C
c.HrAo
Chromium aminocarbenes
)H:c5Hs
CuHu,,
1) BuLi 2) CoHsCHzX
(R)-1
BzCH2 CH3
R-4
t€
'
(S)-2,CO, hv THF
/:--f
(co)5cr\_ il-" .b / X
CH3
? 9t. ,.-\iAN4-..,1o(cH3)3 b CoHs1,'N;-Bt. -cH' [J
1 ,NfH3
( R , S , S ) - 5( 8 7 : 1 3 )
o€
li.
CoHs
.,tal).
(R)-1 can also be convertedinto the (R)-chromium4, which coupleswith the t-butyl ester of (S)-alanine(2) to form the protecteddipeptide5. Cyclopropanation.r Chromium and molybdenum carbene complexes can react with unactivated l,3-dienes as well as electron-rich or -poor dienes (14,91) to form vinylcyclopropaneswith high regio- and diastereosclectivity.In fact' reactionswith alkylmethoxycarbenesresult in a single diastercomer.In addition, cyclopropanation occurs selectively with the least hindered double bond of the diene and more readily with 1,3-dienesthat can adopt the s-cis conformation.
rr,. ::hcnc l, pentacar5 ,:^rnclchromium(0), f .1nlinocstersunder d.r.,.rcrcoselectivity.
Cr(CO)s
+
cH/6crnu
THF 1000
cH34ocHg
"^"1-^",'u ocH3
Mo(CO)5
Bu
ocHg
H
8€'
,ul'z-",r, o
cHs
- ^,J-- -.o1atr;. :: lt o *-Et. ,
CHS
S S '3 (98:2)
ocH3
Cr(CO)s cuttu^ocH,
92o/o
er"r.
82
Chromium
arninocarbenes
time for synthesis carbeneshave been used for some o-Alkoxyphenols'| Chromium dienylcarbenes' chromium to o-alkoxyphenols employs ofp-alkoxyphenols. A novel route under carbon irradiated when prepared as shown, Thus the chromium carbene r, yield' 90% in 2 to cyclizes *t"pt""ed ketene (a) that monoxide is converted t'" " Cr(CO)s 1)BuLi 2) cr(Co)6 3) cH3orf>
rt orovides the oxazinone 2 in good b-v.ch Optically pure 2 can be obtained the chiral auxiliary, effected by h1'drq Reaction with ketene ketak'! Tt ortlx acyclic ketene ketal 2 to give two In 5' and 5 acid to the butyrolactones I rather group selectivity with an ethyl
.ocH3 (co)scr{ 'CsHs *
cHz-
2 CsHs-
n,,"o I rHF I
CHr-
I
ocH3 I .'r,-.. \
-Z\t l l \,,'
c
ocH
[,.o,0.,
eo%
l
x\.
--o
Le
cslls
cl{:
complex active chromium-carbene arylglycines'3 The optically
Optically activl canbe-used Preoaration lo1 rr.. trs,zn'l]z-ffi"" t''-oto'nt"ttethanol' DMAP l, prepared of 1 in CHrCN containing
Thus irradiation of opticallyactivearylgtyJnes' 1) AcBr
t)cu,'-,'. cuH.
N(CH3)4* /.O (CO)sCra^ ,, \'6n5
HzN oH 7e"/"
CoHs
rcgi The reaction was used for a
rCuHu ,O(CH2)2CH=C(Cl.
,uf,ao'.
(CO)sCr< 'CHs
, (CO)sCr{ 'CoHs 1
I nu,"n."*
81% DMAP I CoHs I
1\ chromatograpny
H2N---,COOH ' "H _ cuntu
,i ilr. r0",, 23oloov€rdll
coHs ),,4o
t*Y^o CeHs
(R)-3 (94'l"ee1
2 ( 8 8 : 1 2)
(CO) sCr-- C (OR) R comPkx a carbene I and the stabilized Phc H'Ovield. HYdrolYsisof 3 with (Z)-l'3dr ellene3 rearrangesto a catalystfor this rearrangement'
Chromiumaminocarbenes 83 mc :rmc for sYnthesis nrunr.lienYlcarbenes. drrlcJ under carbon r I ir 907r yield. (COt5
'ocH3
provides the oxazinone 2 in good yield, but modest diastereoselectivity(76% ee). optically pure 2 can be obtainedby chromatography.The final step involves removal of the chiral auxiliary, effected by hydrogenation. Reaction with ketene ketak,a The chromium carbene complex I reacts with the acyclic keteneketal 2 to give two orthoesters,3and 4, which are convertedby aqueous acid to the butyrolactones5 and 6. In the example cited the carbenereactswith high selectivity with an ethyl group rather than a methyl group.
,ocH3 (CO)5Cr{ 'CeHs *
PCzHs
CHz{
C O ,T H F
OCH3 2
coHs---.-1
.:: ;
,oCHs
I Y cHr)-d'ocH,
coHs--lroczHs * l--6^ocn,
76V" )
CH,
4
( aVC6H5 cH3 oH
Addition of y -disubstitutcd halidesadd to RCHO when catr srereoselectivityobtains in add addition of LiI and use of DM? In contrast,addition of 7{isut .rnd stereodivergent(equations
Chromium0l)
iodide
chloride-Lithium
selectivity. Reactionsof chiral allylic bromides with chiral aldehydesindicate that the configurationof the bromide can override that of the aldehyde.This reaction therefore can provide accessto complex chiral adductssuch as 4, which is convertedby standard
I : C
t.25 65'.
oBzt -/cH2
CO2Bzl
CrgHzz
q j )-o
H
CHs
4 steps
Hooc\
.SHt
,,7
c,.Hrr4oAo
CHs
c)-s
rcactionsinto nephromopsinicacid, (-)-5.
CO2Bzl I J. Mulzer,L. Kattner,A. R. Strecker, andP. Luger,Am. C. Schrdder, J. Buschmann, C. Lehmann,
r'
Soc.,113,4218(1991). . ... ,t t 1992),
i
,,,/l).
,l'.'JJition fo crotYl r.r rJes homoallYlic i.'r,,t bcnzaldehyde :;t: ' that this center ril\c itsthe major : .lir.rl centers.An r:.:.ilscs the all-syn
Chromium(Il) chloride-Lithium iodide (l:1). Allenic alcohols. Propargylichalidesreact with carbonyl compoundsin the prescnce of CrCl2 'Lil (2 equiv.) in DMA to form allenic alcohols as the major products.r (Use of other solvents increasesthe formation of homopropargylicalcohols as minor products.)Ester, cyano, or chloro groups have no effect on the regioselectivity,but an a-substituentcan favor formation of propargylic alcohols.
C2H5OOC(CHj3C-CCH2Br+
CrCl2.Lil DMA
C6H5CHO
84"/"
OH | ^.,cHz
c^H^/^'V"
+ CeHsOOC(CH2)3C=CCH2OH
I
(cH2)3cooc2H5 98:2
(""
. Y*tu
cH3 oH 3
Addition of y-disubstituted allylic phosphates to RCHO.2 Both (E)- and (Z\-allylic halidesadd to RCHO when catalyzedby CrCl2 to form anti-homoallylicalcohols.Similar \tcreoselectivityobtains in additions of (E)- and (Z)-allylic phosphates.In this case rddition of LiI and use of DMPU as solvent are usually requiredfor satisfactoryyields. ln contrast,addition of 7-disubstitutedphosphatesto aldehydesis both stereoselective rnd stereodivergent(equationsI and II).
Chromium(Vl)
oxide
I ll (t) HexCHO * er'-,,/VOP(OC2H5)2 I Bu
---
crcl2,Lil 25'
effected with CrO3 in 90% aqueous: dichromate(Na2CrO3)in aqueousH; are obtained with CrO: in CHrCO(
OI H
nr..y'VH.*
"**
vtr2
, \
Bu Pr 99:1
o tl (lf) HexCHO + B]'\a/."'-,'OP(OC2H5)2 I Pr
pr "\
/
OH aoY"
r'^4'{Hex Pr' Bu
v t t /
/
-
CHs
I
'
.-.CHz
1) HBr2B.S(CH3), 2) H,O I
\
rH.C. Brown, S.V. Kulkarni,V.\'
Xl
(ree2).
9B:2 rK. Belyk,M.J. Rozema,andP. Knochel,J' Org'' 57' 40'10(1992)' I. Antes,C.E. Tucker,andP' Knochel'J' Org" 57'6384 2C. Jubert,S. Nowatny,D. Kornemann, ('t992).
Chromium(Il) chloride-Nickel(Il) chloride' lb' when treated with CrClz Cycloenediynols.t The r,r-iodo enediynals la and (14'98)' undergo an intramolecular (5-8 equiv.) and a catalytic amount of NiClz additionofthealkynyliodidetothealdehydegrouptoproducel0-and1l-membered cycloenediynols,isolatedastheacetates2aandZb'Theseproductsareunstable'but2b wasshowntoundergocycloaromatizationto3whentreatedwithl,4.cyclohexadiene. and is believed to be responsible This reaction is typical of .oln" antitumor antibiotics for thc biological activitY.
Cobalt([) acetylacetonate, Co(ace I ntrarnole cular homo D ie Ls- A I a tetheredalkyne group at C2 underg treatedwith 8 mol% of Co(acac):.((
is particularly facile when a 5- or 6 on thermal treatmentof I at l{0-
\
R
Co
\-,.r6na^ (bH,)"cHo lli"i;:)i"'',
,t^\.'t\
i l t l
\/"'aI
OAc
3 1 a ,n = 1 1 b ,n = 2
34o/o 760/o
2a 2b
Letters'32' 31'11(1991)' I C. Cr6uisyand J.-M' Beau,Tetrahedron
Chromium(Vl) oxide (CrOr)' This conversion can be effected in )80% overall RCH:CHz-RCH2COOH'1 H2BBT S(CH3)2' thexylyield by hydroboration of l-alkenes with HBBrz'S(CH3)1' followed by hydrolysis to form torun" lUrefhx), or dicyclohexylborane(HBChx2)' to RCOOH' which can be RCHrB(OH)2. The final step is oxidation of RCHzB(OH)2
1 R=H,n=1 R=H,n=2 R=CHs,n=1
W. Tam,and L.G. Edrl M. Lautens,
Copper(I) iodide-Tetrabutylenr Skipped diynes and triyncs. I rropargylic halides or tosylatess rt
:n DMF or CH3CN.I This reaction
Copper(I) iodide-Tetrabutylammonium
"u^/{Uex . , \
Bd
Pr
99:1
t'F.r, OH
t
87
effected with CrO3 in 90% aqueousacetic acid, pyridinium dichromate (PDC), or sodium dichromate(Na2CrO3)in aqueousHzSOa.In generalthe highestoverall yields (80-92%) are obtained with CrO3 in CH3COOH/H2O.
OH e t t z
chloride
CrO3,
[.ur,.r1ory, ]
CHs
cH,Z)(\He' Pr Bu
cH3cooH, Hzo
1) HBr2B.S(CH3)3 2) H2O
86/"
t'pr"oo,.., CHs
rH.C. Brown, S.V. Kulkarni, V . V . K h a n n a ,V . D . P a t i l , a n d U . S . R a c h e r l aJ, . O r g . , 5 7 , 6 7 7 3
(reez).
98:2 lq.--
J. Org.,57,6384 Knochel,
I l h .\ hcn treated with CrCl2 ::Jcrqo an intramolecular t ..c l0- and 1l-membered ..jucts are unstable,but 2b l( :'.r 1,4-cyclohexadiene. ith rt.l ..licvcd to be responsible N .
Cobalt(I! acetylacetonate, Co(acac)2 Intramolecular homo Diels-Alder reaction of dienynes.t Norbornadienesbearing a tetheredalkyne group at C2 undergoan intramolecularhomo Diels-Alder reactionwhen treatedwith 8 mol%oof co(acac)2,(c2Hs)2Alcl (4 equiv.),and dppe at 25". This reaction is particularly facile when a 5- or 6-memberedring is formed. No reactionis observed on thermal treatmentof I at l4O-170".
\
R
CHz)n
R
Co(acac)2, (C2H5)2AlCl, dppe, benzene, 25'
\.---.16r,r
1s i l
l
7
l
OAc 3
1 R=H,n=1 R=H,n=2 R=CHs,n=1
76/" 64o/o
69/"
\f. Lautens, W. Tam,andL.G. Edwards, J. Org., 57,8 (1992).
rr. ^, rffccted in )80% overall ( l1 , . H:BBr S(CH3)2,thexYl1, .. ,.rcd by hYdrolYsisto form l ( ) l i , l o R C O O H ,w h i c h c a n b e
Copper(I) iodide-Tetrabutylammonium chloride. skipped diynes and triynes. A new route to skipped diynes involves coupling of rrtrpargylic halides or tosylateswith l-alkynes catalyzedby cul, Nacor, and Bu+NCl :r DMF or cH3cN.' This reactioncan be extendedto skipped triynes (equationII).
Copper(I) iodide-Tliphenylphosphine
C u l ,B u a N C l NaCO3,DMF
(l)
Et-----CH2l
,Zuco2cH3 co2cH3
Cyanotrimethylsilane. Cyanosily lation of ald ehy d cs acid catalyst such as Znll or A ethyldiisopropylamineare alst.rh methylsilyl ethers in 90-100'i r tavalent silicate, (CHIIS(CN )\-(( amine. The reaction can proceedi the chiral tin(Il) kwis acid l. pn ( l2-l and 1,1'-dimethylstannocene
H------cH20H
F-cHroH
-;
(tt)
L-CBH1,
CaHrz+CH2Br
T'OS
cBrc/ P(cons)s I
t
7"'"''
11+(CHz)gGOzCHg
-co2cH3
E-QsH17
5'lo/"
--c8H17
The skippeddi- or triynesare reducedto skipped(z,z)-dienesor (z,z,z)-trienesby 4H2O(equationIII)' partialreductionwith NaBH+/Ni(OAc)2' (lll) CsHrz--:\-.-CH2OH
+ (CH3)39(
90o/o
crH,rfficH20H
r S . K o b a y a s h iY , . T s u c h i y a ,a n d T t
fT. Jeffery,S. Gueugnot, Letters,33,5757(1992)' Tetrahedron andG. Linstrumelle, Cyclam (1,4,8,1 1{etraazacvclotctr
Copper(I) iodide-Ttiphenylphosphine. This coupling has been effectedwith Pd catalysts, Coupling of I-allcynes and ArX.t 80-120'. but can also be effectedwith cul/P(C6H5)j (1:2) in the presenceof K2cor at
C6H5l
+
Cul/P(C6H5)3 , K2CO3 DMF,120"
HC=CC6Hs
--;C6H5CH:CHBr + HC=CC5H11-n (Elz=ss'.1)
C6H5C=CC6H5
CoHsCH:Cl-lC=CCsHtr-n (E/Z= 99:1)
1K. Oku.o, M. Furuune,M. Miura, and M' Nomura,TetahedronLetters,33,5363 (1992)'
Epoxidation.t An iron comp of I is an effective catalyst for r or CH3CN. Thus reaction with cr
Cyclam
Cul,BuaNCl D,M F NaCO3
.CC:CH3
82v"
Cyanotrimethylsilane. cyanosilylation of aldehydes.t This reaction has been effected by use of a Lewis acid catalyst such as Znl2 or AlCb (4,542-543). Amines such as triethylamine or ethyldiisopropylamineare also highly effective catalysts, providing cyanohydrin trimethylsilyl ethers in 90-100% yield. Presumably,the reactive intermediateis a penTributylphosphineis as effective as a tertiary tavalentsilicate, (CH3)3Si(CN)N(C2H5)5. amine. The reaction can proceedin high enantioselectivity(907oee) in the presenceof the chiral tin(Il) lrwis acid 1, preparedby reaction of (+)-cinchonine with triflic acid and 1.l/-dimethylstannocene(12,20I -202).
cHz:\i\
7""o^
TfOSnO,,. ttf
---CBHl7
carc/ e(coH5)3 |
-1-.H-
V-CH2Br
/ L-caHrz
: +
.rrcncsor (Z,Z,Z)-trienesbY
I
.llr
l:
osi(cH3)3 /..',-.,..CHO I |
1,c12cl2, -28" + (CH3)3SiCN 630/"
\-/
O^"(90o/oee)
-cH20H
rS. Kobayashi,Y. Tsuchiya,and T. Mukaiyama, Chem Letters, 537,541 (1991)'
-r-r.57s7(1992). Cyclam (1,4,8,1 1-tetraazacyclotetradecane), l.
- , " ' Jrn cffcctedwith Pd catalysts' ts ;.cncc of K2COI at 80-120''
t ' -
l
NH HN
c!-
C6H5C=CC6H5
-
tr.
.) NH HN
CoHsCH:Cl-lC=CCsHrr-n (ElZ=99:1) : ' ' , 1I ( \ t e r s , 3 3 , 5 3 6 3 ( 1 9 9 2 ) '
(1)
(, Epoxidation.t An iron complex preparedby reaction of Fe(CF3SO3)2with 1 equiv. of I is an effective catalyst for epoxidation of alkeneswith Hzoz (30vo) in cH3oH product or cHrcN. Thus reaction with cyclohexeneprovides the epoxide as the main
(RRF erd t!
Cyclobutenediones
OH
I
HzOz Fe(1)(CF3S03)2 -
o"+ 40/"
t i l 17"/o
cHs\--/'o
1) C6H5L| GHs 2) CH3l,Ag2O
"A"
s
6't"/"
o
cHlcH'
CHs
1
cHs
o ceHf\coH,
CeHs
'CoHs + frans-isomer
,Bu
[\-"u^,
o.
bH
3
26%
I L. S. Liebeskind, K. L. Granberg,and J. Zli
high stereoselectivity with only tracesof the allylic alcohol. cis-stilbeneis oxidized with tothecis-epoxide.Iodosylbenzene,CcHolo'cana|sobeusedastheoxidantforthis reaction.
ls,2S-cyctohexanediot. a'])'"o"
\ho"
rW. Nam.R. Ho, andJ.S.Valentine, Am' Soc',f 13' 7052(1991)'
Asymmetric allrylation of P-kao whenprotectedas the acetal2 with tlS selectivealkylation(equationl). Cyclic sulfates,sulfites,15, 105-107; 165' they are now Review.t These products have become of special interest since In addition' of alkenes' dihydroxylation availablc in optically pure form by asymmetric and epoxides of that from differ can the regioselectivityin reactionswith nucleophiles (104 1991 through 1863 from literature covers the yields can be superior.The reference
(t)
p
o$.oo.r.
references). rB.B. t-ohray,Synthesis, (1992). 103-5 2 RX Cyclobutenediones. -98;209-I2O;' 14' 253-254:16' Naphthoquinones from cyclobutenediones (13,9'7 to 2,3-disubstituted t02). Liebeskind et al.\ have devcloped a stereocontrolledroute quinonesfrom2-alkyl.3-alkoxycyclobutenediones(l).ThusadditionofArLitol 2 with RLi followed followed by methylationprovides 2 in 5O-757o yield. Reactionof byaquenchwithtrifluoroaceticanhydrideandNHqClprovidesthccyclobutenone3. followed by oxidaThese products are convertedinto quinones4 by pyrolysis at 140" tion (CAN).
= CH3l = CrsHlgBr
I K. Kato,H. Suemune, andK. Sakai.Icrrd
t R,R)- and (S,S)-1,2-CyclohexaocditL Asymmetric olefination of mahyi cthylidenationof 4-methylcyclohexans
(R,R)- and (S,S)-1,2-Cyclohexanedi(2,2-dimethylprcpyl)amine
""'\1o
OH
I
ll
H
BuLi
61"/"
^/*tutu
oAo
17o/o
cH, Bu,pH
cHs\--/P
1) C6H5Li 2) CH3l, Ag2O
i
bcH.
)L+c6H5 o\ bcH.
87v"
cHf.-cH'
,,|""
cHf.-cH'
1
cHg
c a -r.lv ^ , , 5
2€
1)140' 2) CAN
,Bu
CHg
l\-cu,,
+ trans-isomer
Bu
o b H r\/
?
+ cHs--*Arr,
(c6H5cN)2Pdct2, KOH,CH2C|2
| NO
I O. M. Nefedov,Y. V. Tomilov, A. B. Kustitsyn,U. M Dzhemilev, and V. A. Dokitchev, Mendeleev Comm., 13 (7992).
(CH3)3SnS|C6H5(CH3)2 * CH Z",ZQ
r Y . T s u i i a n d Y . O b o r a ,A m . S o c . , 113.g-Vs rt
Dicarbonylbis(triphenylphosphine)palladium
Diborane. Diastereoselective reduction of 4-ken-2-alkylborate esters (1). This reaction can obtained be effected with several reductants,but the highest diastereoselectivity(anti) is -78' 'THF in THF.' at with BH:
Ct1. ",_,^
9{-Ci
.!.
x
BHs.rHF
'
rHF'-78' >
o-o'tcH. L I
tlt-,,tt.
,"t3t.*
B-/tcH.
Rr
,,
9H l" ?1"r. -
Ri ///\\,//\"\./t
OnC r,
syn-2
anti - 2
a
'rc of HBr. rr .Prcsence x:r-.::.\ activated arenes at room rf - - l. sqc''r Yield). lrss reactive o: f li( l- as catalyst(mesitylene :r .-. hrominated bY I in refluxing l:
.rcld).
l, - . ::, ,,. 33. 6469 ( 1992).
generated n.:...:rJ wirh diazomethane A number l.li{ rr CHrClr/O(C2Hs)2. nc .,', rquallv effective for ex situ and
Rl = CHg, R2= CHg
71o/o
34:1
R1 = CHg, R2 = iPr
89%
62:'l
Rr = !pr, R2= CHs
92/"
>50:1
I G.A. Molander,K. L. Bobbitt,andC.K. Murray,Az. Soc',ll4, 2759(1992)' (1) Dicarbonylbis(triphenylphosphine)palladium, Pd(CO)2[P(C6Hs)3]2 catalyst for this effective most is the I,4-silylstannation of l,3-dienes.l This of (trimethylreaction the Thus (E)-selective. reaction,which can be highly regio- and I). Other (equation (E)-alkene single a provides silyl)tributylstannanewith butadiene are products the and reactive less groups are with more bulky organosilylstannanes obtained in lower yields.
(CO)2Pd[P(C6H5)312
(l) Bu3snsi(cH3)s+ cHNct'
--ffi-
r
(;
(E)
ti(cH3)3
- (E)
(cH3)3Snsic6Hs(cH3)2 *cn/v"',
D..-
1cr. and V. A. Dokitchev,Mendeleev
-"*-
rY. Tsuji and Y. Obora, Am. Soc., f n, 9368 (1991).
ffitic6H5(cH3)2
102
Di-p-carbonylhexacarbonyldicobalt
Dicarbonylcyclopentadienylcobalt, CpCO(Co)2' presenceof CpCo(CO)z' the mono[2+2+2]Cycloaddilion (cf. 12,163).1 In the mixture of epimers' cyclic enyne (Z)-l cyclizesto the tetracyclic diene (2) as a 2:1 (3), and can be The product has the carbon skeleton present in the diterpene stemodin the diterpene'This converted in three steps to an intermediatein a total synthesisof cycloaddition fails with (E)-1'
The yield of the carbonylation-erpan catalyzed by both Co2(CO)s and Ru.tCC (equationIII).
/^-r-\ l
(il) \.,\ru'
l
)
\
d
+ co
CHzCOOCzHs + Ru3(CO)12
This combined catalyst can also effcrt tones to tetrahydroindolizines(equationllll rearrangement(equationIV).
CpCo(CO)z 55"k
(rrr) cH.-Q-cH,
2 (2:1)
@(col
cH2coc(cH3)3
co | (lv, CH3..\N,'
CHs
Co2(CO)e. Rua(COr. | -----;;CH2COC5H5
I J. Germanas, Am' Soc',ll3' 4006(1991)' C. Aubert,andK.P.C- Vollhardt, Di-p-carbonylhexacarbonyldicobalt, Co2(CO)a' by to Ring expansion-carbonylation.t The ring expansion of aziridines BJactams piperidones to a Rh(I) catalyst(r5,82-83) hasbeenextendedto expansionof pyrrolidines by cobalt carbonyl-catalyzedcarbonylation(equationI)'
(r) +R,.
Co2(CO)6 c6H6,02, 220'> co
R1 R1= CHs, R2= CHzCoHs R l = C H s , R 2= C o H s
(-'{^'
.)
nr AttAo Rr 24o/"
Cyclic enediynes. The realization thr an enediynecore which is essentialfor tlx svnthesisof this ring system.One approa'h eldehydeprotectedas the Co2(CO)6adduc conventionalstepsfrom cyclopentene-l--i{ and N(C2H5! cyclizesto 2 in 69% rield
o
* t\ttAol R1 15"/o
oHc
\cotcor.
i
I
t-BuMe2SiO
cH2oH 56"/"
e{
Di-p-carbonylhexacarbonyldicobalt
r :---.nce of CpCo(CO)r,the monoir:- lr as a 2:l mixture of ePimers. hr .r :Jrpcnestemodin (3), and can be ' ' : \\ nthesisof the diterPene.This
103
The yield of the carbonylation-expansionreaction is generally improved when catalyzed by both Co2(CO)s and Ru3(CO)12, dodecacarbonyl-tri-tr iangulo -ruthenium (equationIII).
/^>-1
t t (ll) \-,^-t'
)
an
tt--AttAo t
Co2(CO)8
+ CO
\ cH2cooc2H5
l
I
CHzCOOCzHs
+ Ru3(CO)12 79/o
c: \
This combined catalyst can also effect cyclization of 2,6-dimethylpiperidinylketones to tetrahydroindolizines(equationIII), and this cyclization can predominateover rearrangement(equationIV).
co
2 (2:11
(lll)
Co2(CO)6, Ru3(CO)12 cH.Af^ar. cH2coc(cH3)3
r
| (lv) c H ". A N 2 t
|
r
c
o
l
a^) l
Ru3(co)12, | co2(co)s, \ruA 77yo ,.-1)
cH2coC6H5 -\ .
I l-r. .l(x)6(1991).
t-
c\: :-.rrrnof aziridinesto B-lactamsby c\: :'r\r()nof pyrrolidinesto piperidones Ir s:
lttt
F:
-* " R1 24o/o
-
t
tR'
o
\rAo
-
CeHs
oHc \colcolu
Bu2BOTf NEt3
t-BuMe2SiO l-BuMe2SiO
cH20H 56o/o
*cH.
1o:1
/-\ lll lII ttt^o
|rr.rrCur, l
Cyclic enediynes. The realizationthat a number of antitumor antibiotics contain an enediynecore which is essentialfor their activity has led to extensivemethods for synthesisof this ring system.One approachinvolves an aldol reactionwith an acetylenic aldehydeprotectedas the Co2(CO)6adduct.Thus the keto aldehyde1, preparedin five on treatmentwith dibutylboron triflate conventionalstepsfrom cyclopentene-1,3-dione, and N(CzHs)r cyclizes to 2 in 69Vo yield. Attempted decomplexationwith N-methyl-
l
R1 15"/o
c(cH3)3
Didlt
104
Di-p-carbonylhexacarbonyldicobalt
o9l R3S|CTCCHO + CHoCH-, Coz(CO)o sc
Q,*'*o
1
2(ElZ= >%
CH2OBBu2 3 to 3' Such morpholine N-oxide (NMNO) in cyclohexene results in aromatization agents'2 aromatizationis characteristicof compoundsof this group of antitumor the antibiotic (6) of structure enediyne tetrahydroquinoline the A synthesis of propargylic alcohol with an dynemicint involves condensationof a co(co)6-protected enol.3 Thus treatment of 4 with triflic anhydride and 2,6-di-t-butyl-4-methylpyridine
The uncomplexedpropynal underqocsI Intramolecular Pauson - Khanl alkynyl allylaminochromiumor lung intramolecularPauson-Khand reac-tx
inCH2CI2/CH3NO2resultsin5in52%yie|d.(Useofnitromethaneiscrucialfor iodine provides 6, which satisfactoryresults.) This product on decomplexationwith undergoesaromatizationwhen heatedto form 7'
(co)sM -coocH3 Tf2o, cH2cl2,cH3N02 43o/o
l,M=Cr,W
M.D. Wang and H. Alper,Am. Sr. ll, r P . M a g n u sa n d T . P i t t e r n aJ, . C . S . C h d ' P. Magnus and S. M. Fortt, ibid.. 5JJ t I 'C. Mukai, O. Kataoka, and M. Hanaob ' F. Camps,J. M. Moret6, S. Ricant. arxl J
52o/"
Dichlorobis(cyclopentadienyl)hrhi c ' p l H f C l 2 - A g C l O 4 , 1 5 , 11 9 - 1 2 0 : l C l
7
6
complex I ofProPYnal Diastereoselective aldol reactions of propynals'a The cobalt almost exclusivelY' aldol syn the form (2) to reacts with O-silyl ketene O,S-acetate
Aryl C-glycosides.t This C-gl1c - )-gilvocarcin (a). An unusual feel ('-glycosidation of the A ring. folk Ihus reaction of the t--acetylfucosc,
t'plHfCl2/AgClOa (2 equiv. each) rn ! in 877ayield. This product was cor
Dichlombis(cyclopentadienyl)hafnium-Silverperchlorate
*"'tI::::,
I
+ cH3cH
98: 80 - 85% overall
CHs
RCH2CHO several sleos 467o ov€r3ll
Reaction of 3 with pyridinium of the carbonyl group' is convertedto the aldehyde3' p-toluenesulfonateeffectsdeprotectionofthecarbonylgroupfollowedbyaldolization. Dehydrationofthealdolfo|lowedbyhydrogenationprovidesthetricyclicketone5. Thisproductisconvertedinto(+)-6bystandardreactions.Thiscyclopentannelationto providetheCringproceedswithhighstereo-andregiocontrol'Sinceallylicalcoho|s canberesolvedbySharplesskineticasymmetricepoxidation,itshouldbepossibleto prepare optically active triquinanesby this route'
si(cH3)3
3:ii'"'' sr.
CHa CHs
84"/o
followed by protonolysisand cartrx was used for a synthesisof (*)-tn A lle ny lzirc oniu m reage nts.t allenylzirconiumreagent(a) that rt ctherate to form anti-B-acetvlenic . and anti-p-acetylenicalcohols.a si tbrmed.
CHS
OBzl
1, R = CHzCoHaOCH3-P
coHs4 cHs.-1^cHo Li
t
t
o
:;:tpfi
l
1) CH3CHCH=CHP(OEt)2' 2) BU4NF 94o/"
1) 2) 3) 4\
PyHTs MsCl DBU H2,Pdlc
58%
CHsCHs CHs
CHs
o -so.z.*
CHs CHg
Bicyclizationofl,6.heptenynes.3Treatmentofthechiral3-methyl-1'6-octenyne formed from Cp2ZrCltlBufi $:Z)' t, preparedfrom (+)-citronellene, with the reagent
V. Mori. N. Uesaka,and M. Shihas r{;. AgnelandE. Negishi, Am.Su . I 'G. and E. \q Agnel,Z. OwezarczYk, 'll. Ito, T. Nakamura, T. Taguchi.and
Dichlorobis(triphenylphospine)pc Carbo ny latio n of o-allY Ibc aad :hloride (1) in the presenceof tr ralladiumcatalyst(5 mol %) prorr
Dichlorobis(triphenylphospine)palladium(II)
CH.
o !-
lll
1) "ZrCp2"
acHz-.-.,.i51ocrHu;t
lAI
2 ) H a O * :C O , 73"k
I
\
'rfi
OH
F o
2. >9o%de
CHe H : -
1*:
- severalsteps 46o/o overall
d. .r Rcectionof 3 with PYridinium ir',,uP followed bY aldolization' :':,,rides thc tricYclic ketone 5' h r. This cyclopentannelationto t.:. d --- 'crrntrol.Since allylic alcohols (:. \:.:.lii()n.it shouldbe possibleto
si(cH3)3
o HU
c _
F'
(+) - 3, >99o/oee
2. This product followed by protonolysisand carbonylation,providesthe bicyclic ketone was used for a synthesisof (+)-iridomyrmecin (3)' "Cp2Zr" reacts with propargylic ethers to form an Allenylzirconium reagents.a presenceof BFr allenylzirconiumreagent(a) that reacts in sia with aldehydesin thc to the sy'?addition In ctherateto form anti-P-acetylenicalcoholsas the major product. is usually alcohol nd anti-p-acetylenicalcohols, a significant amount of an a-allenic tbrmed.
OBzl
"Cp2zl' THF.-78"
coHs-{
cHs..1^cHo
3::>epfi RJil
t{''
H-,o
cH'. H
H 2
t{Y
- CHs CHs
:hc chiral 3-methYl-1'6-octenyne rmcd from CPzZrClzlBuL\ (1:2),
o
c-CsHrrCHO BF3O(C2H5)2 76"/"
CHs
CoHs
CoHs ?
49:l
J' Org'' 57, 3519(1992) V. Mori. N. Uesaka,and M. Shibasaki, I c. Agnel and E. Negishi,Am. Soc.,ll3,'7424 (1991) 'c. Letters'33' 1543(1992)' and E. Negishi,Tetrahetlron Alnel, Z. Owezatczyk, 'H. It;, T. Nakamura, ibid'' 33' 3769(1992)' T. Taguchi,and Y' Hanzawa,
Dichlorobis(triphenylphospine)palladium(II)' (600 psi) of o-allylbenzyl Carbonylation of o-attylben4yl halides't Carbonylation in the presenceof this and (2 equiv') ;hloride (1) in the presenceof triethylamine (2) in 78o/oyield' lactone enol benzoannelated the ralladium catalyst(5 mol %) provides
rtz
Dichlombis(triphenylphosphine)palladium(II)
.Z\\.,//\r\r
r
t t *cHz
iT
,-,
l
- Copper(I) iodide
CO'N(C2H5)3
Pd(il) 780/"
(') u
Bu2MePy 9 o H Tf2O, cH2ct2,25' _
63v"
orf (D )-.,o,
=cH,
.orf
t_/
c
a
+ Hl
(E)-1
cl
HO-----.
sevefal steps
?tt orr
tr
.
,)fJ:,
(z)-1
of theantiulcer in a synthesis A similarreactionwith 3 gives4, whichis an intermediate agentu-68,215(5).
and 2 equiv. of diethylamineto givc thc tl ,nd (Z)-2 exhibit comparablecytotoxitr K. Arai, K. Yamada, andS. Tcrr K. Nakatani,
rG. wu, I. Shimoyama, J. Or9,56,6506(1991)' andE. Negishi, -Copper(I) iodide' Dichlorobis(triphenylphosphine)palladium(II) be coupling of dienol tlitriflates and propargylic alcohols.t This coupling can dicyclic the used to obtain open-chain (E)- and (Z)-dienediyne diols, analagousto enediyne system of the neocarzinostatinchromophore,responsiblefor the cytotoxity prepared of the antitumor antibiotic. Both (E)- and (Z)-dienol ditriflates (1) can be couple ditriflates from 2-formylcyclopentanoneas shown in equation(I). The dienol of cul, lo% catalyst, with propargylic alcohols in the presenceof 5 mol vo of the Pd
Dichlorodimethylsilane, (CHr):SiCl:. Reductive coupling of RCHO aad cll. uracil (5) involves a novcl coupling of u * ith dichlorodimethylsilane.Thus treatnrr bcnzeneselenoland (CHr)2SiCl: (cxccs:s n 927a yield as a mixture of epimcrs tl *ith Bu3SnH and (C2H5)BI follo*c'd br
ll3
Dichlorodimethylsilane r
I
,dide
-'-\.-O. ^-'--,ry
l F o
(l) tr
nv (cH3)2c=o
Tf2O,Bu2MePy
? o H cH2cl2,25' 63"/"
oTf
?tt orr
tr
(z)-1
( E ) -1
oTf
. X:;" (t)2-.€\^-. 'orr \--l HccH3
P d ( l l ) ,C u l , DMF NH(C2Hs)2, 91"/"
(E)-1
9Hs HO CHs CHe
{
- -oH '{
?tt orr
tr
.,x::"
CHs CHs ,CHs CHs
(z)-'l
rc-- . .:r.llcin a synthesisof the antiulcer
and 2 equiv. of diethylamineto givc the (E)- and (Z)- dienediynesystem 2. Both (E)tnd (Z)-2 exhibit comparablecytotoxity. (1991). :K. Nakatani. andS. Tcrashime,TetrahedronLetters,32,3405 K. Arai,K. Yamada,
y-(,,pper(I) iodide. coupling can be 13tltc alcohols.r This cyclic ditr.'- .lr,,ls.analagousto the cytotoxity trl : :i. rcsponsiblcfor the prepared ir-.:.:r,'l tlitriflates(1) can be dienol ditriflates couple luj' :: rl). The rrf the Pd catalYst,107oof Cul' :'
Dichlorodimethylsilane, (CH1)2SiCl2. Red.uctivecoupling of RCHO and allylic alcoholst A synthesis of tunicaminyluracil (5) involves a novel coupling of an aldehydewith an allylic alcohol, effected s ith dichlorodimethylsilane.Thus treatmentof the alcohol I and the aldehyde2 with benzeneselenoland (cHr)2Sicl2 (excess) in pyridine at 23' provides the product 3 n 92Vo yield as a mixture of epimers (1:1). Radical cyclization of 3 in acetonitrile *.ith Bu3SnH and (C2H5)B3 followed by siloxane hydrolysis provides the protected
ll4
Dichloro(ethylene)platinum
dimer
D
\HAC CH3O,,,./,,--y'lOMEM t l o-r.t\^,.
R3S|O\
/D
A]-'
lCt
(,
l l " "
rBSd brrso
CHz 1
2
o
C6HsseH (cH3)2sicl2 Py,23"
t(
R3S|O\A
,r7c"^u
*'r",
92"/"
CHs
1 ) B u s S n H(, C 2 H 5 ) 3 8 2) oH
AcNHz,,.
oH oH
>
o
o
indicatesthat rearrangementinvolves inre
*'rt,
I K. Ikura,I. Ryu,N. Kambe,and N. SoncJr .
CH3O"''\O : TBSO
t O OTBS
a ( 3- a : 1 )
o 'PMB
Diethylzinc-Chloroiodomethane, (C:H. I Cyclopropanation ofalkenes.t Thc ! from diethylzinc and CH2I2,and presuma reagentpreparedfrom (C2H5)2Znand (l
the usual Simmons-Smith reagent. pan rclvent. Moreover,cyclopropanationof alh t equationI).
OH derivate 4 of tunicaminyluracil (5). rA.G. Myers,D.Y. Gin,andK.L. Widdowson, Am- Soc.,f13' 9661(1991)'
Dichloro(ethylene)platinum dimer, IPt(C2Ho\Clr]2, Zeise's dimer (l)' Isomerization of silytoxycyclopropanes to allyt silyl ethers.t This Pd(lI) complex effects isomerizationof silyloxycyclopropanesto allyl silyl ethers. The last example
(t)
'-\
rc,/{ m
(/
S . E . D e n m a r ka n d J . P . E d w a r d s J. . O r e . . *
Diethylzinc - Chloroiodomethane
D R3S|O\ ]l--D
-"vo \- "J.."-'(. PMB
/
: o ores
lsa
1 , C D C | 32, 0 "
R3S|O. ,H
/-Y"o'
rK]-t (-J
\-,
2 SeC;Ht
?siR3
1,cHcl3
R3S|O-n Pr/
-czHs
11s
,,/tY'"^'
8a"/"
CzHs
) - -: :-\ ^,
cH3\Y.cH3
t\
"tr>_l\
H l osiR3
2v
OH
l . '--r,
-
n -^^/i
:
nssio)-,,'--r. H
indicatesthat rearrangementinvolves inversion of the silyloxy group.
o
rK. Ikura,I. Ryu,N. Kambe,andN. Sonoda, Am. Soc.,ll4,1520 (1992).
'-- o OTBS
4 3 - 4 1)
) F ^
cH3-y'cH3
o 'PMB
rc
Diethylzinc-Chloroiodomethane, (C2Hs)2Zn-ClCHzl (l)' Cyclopropanation of alkenes.r The Simmons-Smith reagentis generally prepared from diethylzinc and CH212,and presumablyis (iodomethyl)zinc,lCHzZnX. The related reagentprepared from (C2H5)2zn and clcHzl in the ratio 1:2 is more reactive than the usual Simmons-Smith reagent, particularly when used with dichloroethaneas solvent.Moreover,cyclopropanationof allylic alcoholscan show high diastereoselectivity (cquationI).
5
OH l H
OH (C2Hs)2Zn- ClCH2l,
(t) r
l l - r . ) 6 f r (l 1 9 9 1 ) .
t r l
ctcH2cH2ct,0'
a'Y.\,{
H
(99% de) r ' u ' 't . c ' . d i m e r ( 1 ) . hl ,tltl erhers.r This Pd(II) complex I , . i . i l r l c t h e r s .T h e l a s t e x a m P l e
1 S . E . D e n m a r ka n d J . P . E d w a r d s ,J . O r g . , 5 6 , 6 9 7 4 ( 1 9 9 1 ) .
116
(BINOL) 2,2/-Dihvdmxv-1,1/-binaphthyl
(Simmons-Smith reagent)' Diethylzinc-Methylene iodide allylic alcohols Cyclopropanation of substituted Asymmetric cyclopropanation't
1)f.41 2) Cfi/
(1)attachedtoacarbohydratederivedfromo.glucosewith(C2H5)2ZnandCH2I2(excess) canproceedwithhighoius",.o,"t""tivity.Thetriflateoftheproduct(2)whenheatedin
OBzl
(C2H5)22n,CH212 -35' - 0" >97"/o
(,?u'u oJ"'
1) t-BuLi(3 equiv.)
"roH OBzl
\/
\.,,
2 (>50:1 de)
1
r* a
OBzl 1) Tf2O,PY 2) DMF, H2O,
Ho,-,..yzcaas 4 (90%,98.4%ee)
3,3/-DiarYl BINOLs can be obtaincd * BINOL followed by Suzuki coupling rth (equationI)'
: 1) BuLi (3 equiv.) 2\ BTF2CCF2BT
(t) 4
\
of the cyclopropylto the aldehyde3 with release aqueousDMF undergoescontraction methanol4.NotethatthepresenceofthefreehydroxylgroupatC2oftheglucopyranoside of the product 2' I is essentialfor the high diastereoselectivity lA.B.Charett,B.C6t6,andJ.-F.Marcoux'Am.Soc.,rl3,8166(1991).
(BINOL)' 2,2/-Dihydroxy-1,1''binaphthyt 3-and3,3I-Substitution.Thedirectedortholithiationroutecanbeusedtoeffect3or carbamates' by use of the MOM or SEM ethers and 3,3'-functionalization of BINOL (THF, -78')' t-Buli of equiv. 2.2 is best lff.",.d with Generation of the monoanion G e n e r a t i o n o t t h e d i a n i o n i s b e s t e f f e c t e d w i t h 3 . 0 e q u i v . o f Bconfiguration' uLi(ether,25").This proceedswith retention of method when applied to lS;-sfNOf-
OMOM
4,4-Disubstitutedbutan4-olidcs'by additionof Gngna cnantioselectivity .ruxiliaryBINOL.The reactioncan prtx
(BINOL) 2,2i-Dihydroxy-1'l/-binaphthyl
tt7
i. :.- ill I
o:' ' "f substitutedallylic alcohols rr .\ '- | ('1H.)2Znand CH2l2(excess) n-.'. : ihc product(2) when heatedin
1) l-BuLi (2 equiv.)
,l qd-
710/o
6,?u'u oJ''' 'rroH
2 ( > 5 0 :1 d e )
HO-=//>.C6Hs 4 (90o/.,98.4"h ee)
of 3,3/-Diaryl BINoLs can be obtained by conversion to the dibromo derivative Pd[P(C6H5)3]a by mediated BINOL followed by Suzuki coupling with arylboronicacids (equationI).
Br 1) BuLi (3 equiv.) 2l BIF2CCF)BI
OMOM
84y"
OMOM
(t) tr ..- -r * irh rclcaseof the cyclopropylh \ . ir(rup at C2 of the glucopyranoside i ',:':,rduct2' nr 11991)
":t.'tion routecan be usedto effect 3'-- \1o\1 or SEM ethersor carbamates' -78")' q I I cquiv. of l-Buli (THF' This 25")' (ether, r: : rquir'. of BuLi 'rl(nti()n of configuration' s
c6H5B(OH)2 Pd(0)
Br
tsi(cH3)3 cH3cN
I
in high 4,4-Disubstituted butan-4-olides.2 Products of this type can be obtained the chiral (R)-1, of esters, inantioselectivityby addition of Grignard reagentsto 7-keto induction. .iuxiliary BINOL. The reactioncan proceedwith high 1,7-asymmetric
ll8
2,2tDihydroxy'1'l''binaphthyl
(BINOL)-Triphenylborate
o&o-cH. o'?o o
"11dll, ry*
+
B(OC5H5)3
(S) - 2' 95% ee
(A".ru
(R)-1
CH2\,,C to the use of 1'1/-binaphthyl is a general introduction Review.3 This review from 1974 to 1992' uu*iUu'lt'; 86""f""n"t' derivatives as chiral
*':?.it;?"it , retrahedron andv. Snieckus 1p.J.cox,w. wang, MiYano"J.t S and 2 y. Tamai.M. Akiyama'A Okamura' 3c. Rossini,L' Franzini'" #;;;;';Jp'
(l)
C6H5CH=NBz|
+
ocH3
ou un rl. l)1,)]).,
s03 (19e2)' sutuuao'i'svnthesis'
ta srnr Jienc promotedby (R)-1' generated ': fhis asymmetric Diels-Alder reaoion comof this organoaluminum
2,2/-Dihydroxv-1,1/'binaphthyl-TFimethvl".t:1tl:l;"
j.""1',"".##*'?i"J"'"hvdes'. *";r::Ixxfx::;;'::::;;[, -2- oxai form cis-4-alk oxY
CH2\,.OS .
( ocH3
)-l A)^o\ocH'
C6H5CHO
1' CH2C|2'CH3CN 0" ---;;;-
cH3o'^\y'
cis-3
,lkaloid derived from nicotinic acid' lbata' Tetrahedron I H. Suga, S. Shi, H. Fujieda, and T
(1991)' Leners' 32' 691 I
',''";:l:::li::;i:::l;I,:Hl:l"Tl"-reac,ioncanbeeff
ectedinT2-e0v.
with reactionof (R)-BINOL io'on reagentr' p'"pJuy "n'J the with Danishefsky and the eeby catalysis Thu-sreactionoi un uldinlin" (jt'ii)"^ii':' triphenylboratein
J' Ort 57 K. Hatltoriand H. Yamamoto'
t)ichloroketene. Ct Indolizidines; quinolizidines't gent'ntt (l) \-bcnzyl-2-vinylpiperidine
Dichlomketene
o
"\Yill,
r9a t: -
ll9
+
B(OC6H5)3
B-CnHq
o
(S) - 2, 95% ee ( R ) -I
l l L . .-l
z
-l-l
( ' t .-
' thc use of 1,1/-binaPhthYl r r r1 9 9 2 .
C6H5CH=NBzl
.
rr5.r(1992).
l r l Bzl
2, B5o/oee
dienepromotedby (R)-1, generatedin situ, providesthe adduct2 in 85o/oee (equationI). This asymmetric Diels-Alder reaction can be used to prepare (-)-anabasine (5), an
r(-'
L.C-o
o
ocH3
:
cH3cN 1, cH2cl2, 0"
1 , 4 4M . S . c{zct2, -78"
cuHu4f-
:tnr. Comm., 687 (1992). , 503 (1992).
!m. F- -. - rrf this organoaluminumcomto ;\, 'JJition with arYl aldehYdes lt:
(l)
cH2Y'oSi(CHs)s /
1
o
71v"
Bzl/N
77.7"/"
poocH3 -\ {:C
)1 oA"uru
'".a) trans - 3
. r 2 .6 e lI ( 1 9 9 1 ) .
5, tts = -79.2"
:lkaloid derived from nicotinic acid. J. Org., 57,3264(1992). K. Hatltoriand H. Yamamoto,
: Ir\ '- i!ri()ncan be cffectedin72-90Vo ;p.--.1 hv reactionof (R)-BINOL with | , : ,:r .tldimine and the Danishefsky
Dichloroketene. Indolizidines; quinolizidines.r Generation of dichloroketene in the presence of \-benzyl-2-vinylpiperidine (l) generatesan intermediate(a) that cyclizes on warming
l2O
Dichlomketene
to the 10-memberedlactam 2. A silnilar reactionwith the N-benzyl-2-vinylpyrrolidine (3) provides the 9-memberedlactam 4' 2,6-Dichloropyridine N-oxide,
CtA
X
o
i'tl
(^l^"t,
25"
cl2c=c=o
Oxidation.l In the presence of ruth RuTMPOz, and a trace of HBr or HCl. 1 secondary alcohols at 25" in high I ield Adamantaneis oxidized mainly to the l-hrt (15-25Vo) and adamantanone-2(7-21 '1zn
\....,.N-.._..C6H5 1
,"--rAcH" t
l
cl
60'
\.--rya"cctt
CI
Bzl I
oCH.
a
t "
z--zl\CH, ( l \--N..,-CuHu
ct2c=c=o
cl cl
25" 64"/"
..) t
l
RuTPP(CO).H& benzene.20'
+
1
*1
ft""u cyclization and Exposureof either 2 or 4 to 12or c6H5SeBr triggers a transannular quinolizidines(5) from 2 or dcbenzylationkr providc iodo- or phcnylseleno-substituted the analosousindolizidines from 4.
OH .\
t
2
-
12,50" 857"
I E . D . E d s t r o m ,A m . S o c . ,f 1 3 ' 6 6 9 0 ( 1 9 9 1 ) .
cl
l
Il. Ohtake,T. Higuchi, and M. Hirobe. .{a .S
CI
ldisilou I J- Dichloro-1,1,3,3-tetraisopropy t(cH:):cHlzSi(cl)osi(cDcH(cH.):l:I lt Regio- and stereoselectivedihfiranl I exclusivelywith the isolatedcvcloallc \\'hereasdirect osmylationof 2 providcs
1,3-Dichloro-1,1J"3-tetraisopmpyldisiloxane
\ -benzyl-2-vinYlPYrrolidine
,-\
/\i -l-l ClN-o*id", 2,6-Dichloropyridine
l2l
l-Cl
o
(1) Oxidation.r ln the presence of ruthenium porphyrin oxo complexes' such as RuTMPOz, and a trace of HBr or HCl, pyridine N-oxide I can oxidize alkanes to secondary alcohols at 25' in high yield. The reactive intermediate is not known. Adamantaneis oxidized mainly to the l-hydroxy derivativc (68Vo);adamantane-1,3-diol (l-2%) are minor products. (15-25Vo')and adamantanone-2
cl cl
CHa
I '
cl cl
.^> l
l
R u T P P ( C O )H, B r benzene,20'
+
1
'x"* (,
94o/o
ri\
",A*A",
o
*1
ft""u cyclizationand t : - - :. .r transannular u--
C6H5COCH3
o
OH
.:rd quinolizidines(5) from 2 or
.\
t
l
a\ t
l
I
H
.-\
l ^ l I z9l
N -.-4.,
:H. Ohtake, T. Higuchi,andM. Hirobe,Am.Soc.,114,10660(1992).
l " ' o 5
I J-Dichloro-1,1,3,3-tetraisopropyldisiloxane(TIPDS-Cl2), 1' [ (CH: ):CH]zSi(CI)OS(CI)CH(CH:)zlz $6,r2s 126). Regio- and stereoselective dihydroxylation.t This reagent adds to the oxepin ! exclusively with the isolated cycloalkene double bond to provide 3 (84Vo yield) Whereas direct osmylation of 2 provides a mixture of diols in low yield, osmyla-
(Diethylamino) (phenyl)oxosulfonium
methylide
CoHs
1
.98o/oae
R = n-CeHrz
o
(2s)-hydroxl keto DIBAH (2 equiv') to the to the 'rt converted be can de). The products (Evans n ammonium triancetoxyborohydride of 2'3-epry Regioselectivereduction pure 3-all enantiomerically "on r"r*d into -15 - l at CH2CI2 in equiv.) (3 oi"O"
Raney Ni
oH 9H l . cH.McH. (R'R) - 4
andN' Ogunr'Srd I M. Hayashi. T. Yoshiga' : t,t. gisct,,Z.-R.Liu, and M' Singh'J t)rt ' La ti. sorruaieandN. Ghiatou'Tetrahedma 'J. M. Chong,ibid', 33, 33 (1992)' t i.'1. cor"ylnd G' B' Jones'J' org" 37' ltt ( I S,2R,4S,5R)-2,5-Diisopropylcyclobcr PreParation.r'
(cH3)2cH\, HO
(D Ior ct Chiral titanium catalYst ansa-bis{tr chiral titanium catalyst,an of I T ith reaction of the dimesylate
(1) 125 (1s,2R,4s,5R)-2,5-Diisopmpylcyclohexane-l'4-diol
a:-
^llopriate choiceof i-BuzAlH ::rioselectivitY to the PrimarY -rJuced bY i-Bu2AlH mainlY
0:
.-.li()nto the PrimarYalcohol' .: :norides. PhenYl-substituted . Rcductionof theseePoxides
Ir lc.
I
2 with high diastereoselectivity (>95Eo DIBAH (2 equiv.) to the (2S)-hydroxy ketone anti-l'3-diol4 by reduction with tetramethylde). The products can be converied to the reagent) followed by desulfurization' ammonium triancetoxyborohydride (Evans These epoxy alcohols can be Regioselective reduction of 2,3'epory alcohols'a by reduction of their tosylates with converted into enantiomericalli pure 2-alkanols -15 - 25"' DIBAH (3 equiv.) in CHzClz at
Illl
I
9H
DIBAH
CHr +
..nQ
RCH2CH2OH
n-C16H21,.MoTs
CH
-/.\ "illBilt, n-crcH21,"-ycH3 + n-C'roHx' ) I s7"^ 6t ,, : 3 CHs >98o/oee
>98% ee
OH
100:1 0: 100
t-"ttlt ^\.,^ors o '
0: 100 65:35
18:82 bY : \fto sulfoxides(1), PrePared bY reduced are :,,lucncsulfinate,
=-
O H ? ? cHa*tti't'* 1 (CH3)4N.HB (OAc)3 HOAC
l:-
.-n-c,0H2.,^-] n-c1oHz1"'\Y,,ltt
sso/'
6H
94:6
cHs
ethers are ethers's /-Butyldimethylsilyl Reiluctive cleavage of t-butytdimethylsilyl DIBAH by cleaved reductively Uut they can also be generallycleaved by fluoride lon' yield' in84-917o alcohols to yield the corresponding in CHzClz at23'in1-2 hours
97:3
h\
---^: +
9O"/"
I M. Hayashi, T. Yoshiga'and N Oguni'Synlat'-41,9 .(1991)' ';;, 57' 1618.(1ee2)' t;.; Z.-R.Liu, andM' Singh'J' org'' 1605(1992)' 33' r G. Solladi6andN' Ghiatou'Tet'ih"d'onLetters' (1992)' t J.M. Chong,ibid', 33, 33 J' Org'' 37' 1028(1992)' ti.l. co..y1nd G B' Jones' (1)' ( I S,2R,4S,5R)-2,5-Diisopropylcyclohexane'l'4-diol , PreParation.r
(CH3)2CH6...OH
t
l
Ho"'\^cH(cH3)2 OH 9H I ' cn3,McH3 ( R ' R )- 4
of alkenes'z The enantioselec.tivekomerization Chiral titaniun catallst Q) for the dichloride (2)' is preparedby conchiral titanium catalyst,t"l"'-OOtt"denyl)titanium is that product form a of r wiih indenytlithium to rcaction of the dimesyrut.
DimethYlsulfoxonium
methYlide
cH30
o
CH3O
Hs o.(
1
cH3o
v e r t e d i n t o 2 b y r e a c t i o n w i t h B u L i a n d t h e n w i t h T i C l l i n Tfrom H F athe t - . isopropyl 7 8 . 6 5 . . Agroup' single indenyl groupsare placedaway product is formed in which the the isomerization of the LiAiH; (4 equiv ) can catalyze This reagent, when rcduced by in 767o ee' product only 1i1 to 1S;-l as the meso-trans-4-butyf-f-uinyf"ytiohexane
NHCOCH3 (! 4)
(""
a\ t YI
1, L|AIH4 mesitylene,23'
l
c(cH3)3 3
(cHt ll
100"/.
-
I
c(cH3)3 (s)-4, 76ol"
l-"tr--.
I (A , ll . I
l
"t"t.,] (R)-4
r M . G . B a n w e l l ,J . N . L a m b e r t ,M . F \ l e c l r t
(teez).
Dimethyl sulfoxide-Triphosgen€' Triphosgene(CCIIO)2C:O. is a rcad Ofidation.3 This combination(l t rs rmall- and large-scaleSwern oxidatttns
H H
crHr-+cH2oH 1Z. Chenand R.L. Halterman,Synleu'142(1990)' 2ldem,Am. Soc.,114,2216(1992)'
DimethYlsulfoxonium methYlide' C y c l o p r o p a n a t i o n ' , T h e k e y s t e p i n a b i o m i m e t i c s y n t h e s iin s oseveral f ( + ) . c osteps l c h i cffom ine(4) reactionof the tricyclic l, prepared is a regio_and stereoselective 5-bromo-2-methoxyphenol,withdimethylsulfoxoniummethylidetogiveasingleproduct ( 2 ) i n l 5 a o y i e t d . W h e n t r e a t e d w i t h t r i f l u o r o a c e t i c a c i d a tproduct 2 5 " , t h i sisp rconverted o d u c t f e a into rlanges O-methyl ether 3' This in 897o yield to the a-tropolone (+)-colchicine (4) in four known steps'
/-*'r*,
H. EckertandB' Forster,Angew'Chen It .tldrichimicaActa, 21, 47 (1988)' C. Palomo,F. P. Cossio,J.M Ontoria'arrJ
l2-Diphenyl-1,2-ethanediamine. lG l: Asymmetric sYnthesisof l)'dbJt rcactionof (R,R)-l with a l,2-dione to
1,2-Diphenyl- 1,2-ethanediamine
127
H2CSO(CH3)2 D M S O ,1 8 '
ltt
*, c
I
I'HF at -78 -. 65". A single :'.\av from the isoProPYlgrouP' :.rlrzcthe isomerizationof the
cH3o
,'nl)' product in 76Voee'
NHCOCH3
cH30
(1 4)
t.\
r M . G . B a n w e l l ,J . N . L a m b e r t ,M . F . M a c k a y , a n d R . J . G r e e n w o o dJ, . C . S . C h e m .C o m m . , 9 7 4
tl
(tee2).
n: 72' ..
I c(cHs)s (R)-4
Dimethyl sulfoxide -Triphosgene. (CClrO)2C:O, is a readilyavailablersubstitutefor phosgene.2 Triphosgene Oxidation.3 This combination(1) is comparableto DMSO-oxalyl chloride for both small- and larqe-scaleSwern oxidations.
H H
czHs#cH2oH
1, N(C2H5)3 -78-0'
l l /FN. O' PMP
(4) n '- -' . .\nthcsisof (a)-colchicine l. prcparedin severalstepsfrom 1. n:.-- 'le th\ lidc to give a singleproduct :rr. ,-rJ et l5', this product rearranges b(' .r lhis product is converted into
H H
c2Hs+_j-cHo l l /FN, OPMP
ll. Eckertand B. Forster,Angew.Chem.Int. Ed., 26,894 (1987). - .lldrichimicaActa, 21, 47 (1988). (1991). J. Org-,56,5948 F.P.Cossio, J.M. Ontoria, andJ.M. Odriozola, C. Palomo,
lJ-Diphenyl-1,2-ethanediamine, 16, 153-158. Asymmetric synthesis of 1,2-diamines.t This synthesis involves as the first step :!'actionof (R,R)-l with a 1,2-dioneto form a dihydropyrazine(1,2-diimine,a), which
lza
1,2-Diphenyl-1,2-ethanediamine
can be reducedto a piperazine2 by various hydride reagents.The highest diastereoselectivity obtainswith NaBH:CN and an acid catalyst,pyridinium p-toluenesulfonate,in CH3OH at -30', which affords the diaxial product (2). Reductionof the C-N bonds can be effectedby acetylationand cleavagewith lithium/NHr. Somewhatbetter results can be obtained by conversion of 2 to the biscarbamate3 by reaction with isobutyl chloroformateand cleavagewith LilNH3. This 1,2-diaminederivative is cleaved to the
-;
cH3"\"'\oi'--t" (E)-2
I
(S, S)-1,N(C2Hs)3 | hexane I C6H5CH3,
bishydrobromidesalt 4 in 68% yield and 99Vo ee.
I
9BR'* I
c6Hs\ NH,
faoHsn-ru1-cHsl | | | \ll CH.l LauHru"
+ C H 3 C O C O C H 3+ l
|
CoHu."'\*r, ( R , R )1 -
PPTS NaBH3CN, cH3oH,20' _ SSYo
1)CICOO-l-Bu 2)Li/NH3
o\ | \
a
H C6H51.-N--7rCHs | I C6Hur..'\;r1l",rata H 2
NHCOO-l-Bu I
cHs\-AcHs : NHCOO-r-Bu (R,R)- 3
1)-2oo | CH"^
ll-cH,
2) H2o _ 650/o
H{
"'
ery
(E,z)_3 H
coHsr..-N._acHs + 15:1
HBr,AoOH 80"
l
l t'-t'-at. CoHs"" H
of allyl alcohol itself, but rearrangemcnrof r: proceedswith high enantioselectivin..
Enantioselective Darzens reaction.-' Rr hvdeswhen promotedby (R,R)-l resultsin ar can be debrominatedby Bu3SnH/AIBN or err
HBr.H2N
tttfcH. t : HBr.H2N (R,R)- 4, 99o/"ee
Asymmetric lreland-Claisen rearrangement.2 The chiral diazaborolidine S,S-1 rearrangementof allylic esters.This can effect highly enantio- and diastereoselective reagenthas previously been used to convert (E)-crotyl propionate(2) into the (E)- or (Z)-enolate(3) dependingon the solvent and the base(16,155).Thus 2 is convertedinto (E,E)-3 by reactionwith I and ethyldiisopropylaminein CH2CI2in CH2C|2at -78". On standingat -20" for severaldays it rearrangesto the threo-acid4 in >97% ee. Reaction of 2 with I and triethylamine in toluene-hexane results in (E,Z)-3, which rearranges at -20' to the erythro-acid 4 tn >967o ee. The by-product of rearrangement is the bis-sulfonimide precursor of 1. Lower enantioselectivityobtains in the case of esters
d
o CnHqCHO +
N'Q
ll
BrcH2
oc(cH3)3
KOC(CH3)3 HOC(CH3)s
CoHs
OC(CHJ3 3, oe-140o
rith base.Theseepoxidesare easill con\cno irc easily reducedto B-amino a-hvdrorr cs
1,2-Diphenyl-1,2-ethanediamine
-l'he highest diastereose:..," 'rum in t\- : P-toluenesulfonate. honds C-N I R-.:rcrionof the rr \ ll,. Somewhatbetterresults r:'. .r hr reaction with isobutYl n: -. .icrivativeis cleavedto the
(S,S)-1,1-Pr2NC2Hr, ?8R.2 cH^cr,.-78o , 6-\.-cHs
o -
t
l
o'A\"-cH3
cH.,.\.,.
%CHs
(E)-2
(E, E)-3
I( S ,S ) - 1 ,N ( c 2 H 5 ) 3 |
I
r,-ro" I ,rr,ol'u"'"
hexane C6H5CH3,
i
l. Hs
3.Hs
OBRr*
t
*Y"'1
-
?- "" )l -cH,
ru^cH'l a
129
1) -20o 2) H2O > 65o/o
I
o
o
,o\.""t.
,o\c"
cHzx-/',rcHs
cHzx2.,rcHs
erythto-4 (>960/"ee)
threo_ (>g7o/oeel
(E,Z)-3
H C6Hs1.N-"eCHs
t
\*'-"t. CoHs*'' H
6r
of allyl alcohol itself, but rearrangementof various allylic propionateand butyrateesters proceedswith high enantioselectivity. Enantioselective Darzens reaction.s Reaction of l-butyl bromoacetatewith aldehydcswhen promotedby (R,R)-l resultsin an anti-adduct(2) in >91Va ee. The product can be debrominatedby Bu3SnH/AIBN or convertedto a glycidic ester(3) by treatment
H B r . H 2t N
e'
l
-
cH.-=AcH. : (R,R) - 4' 99o/oee
(RR , )-1,
o
HBr.H2N C6H5CHO+
Jl-oc1cH.;.
BrcH2/
N(CcH97Vo ee' Reaction c\- '. rn (E.Z)-3, which rearranges is the lr,:: 'Juct of rearrangement trr '. ',htainsin the case of esters
N . O
KOC(CH3)3 HOC(CHds
82/"
f" ll cuHu-^)i^oc(cH3)3 75"/" :
NaN3
coHs
oc(cH3)3 3, ct6-140o
OH 4
with base.These epoxidesare easily convertedto B-azido a-hydroxy esters(4), which are easily reduced to B-amino a-hydroxy esters.
130
(S)-(+)- or tRx - r
(&R)-1,2-Diphenylethane-1,2-diol,dimethylether
Asymmetric synthesis of B-amino acid esters.4 The chiral diazaborolidine I (16,155) also effects diastereo-and enantioselectivereactions of (S)-r-butyl thioproponoate (2) with N-benzyl or N-allyl aldimines 3 to form B-amino acid esters 4, precursors to chiral trans-B-lactams (5) in 9O-99Vo ee.
"r.? lf-*
r--Y -'-O'-O
+ rY'\ \--\,2 I
LJ 2,R=c-CoHrr
C6H5CH=NCH2CH=CH2 3
*
(s,s)-1, N(c2Hs)s
o tl
C6H5CH3, hexane, -78"
cH.cHrAsc(cH3)3
CH2=61611'N O t t l ceHs/-lAsc(cH3)3 = CHs
r-BuMgX
R'N4 ,
O
L_l'cn, c"(,
4 (antilsyn = >99:1)
5 , 9 0 %e e
I M. Shindo, K. Koga, and K. Tomioka. .{r I M. H. Nantz, D. A. Lee, D. M. Bender, and A. H. Roohi, J. Org., 57, 6653 (1992)' 28.J. Corey and D.-H. I e,e,Am. Sac., ll3, 4026 (1991). 38.J. Corey and S. Choi, TetrahedronLetters,32,2857 (1991). a E. J. Corev. C. P. Decicco, and R. C. Newbold, TetrahedronLeuers, 32, 528'7 (1'991)
(&R)-1,2-Diphenylethane-1,2.dio|, dimethyl ether (1)
c6H: CH3O
,cuHu
(S)-(+)- or (R)-(-)-Diphenyl(l-merbla E nantios elective cyanomethy latiu-l action of BTCHzCN with ZnlCu. adds t cquiv.) to give B-hydroxy nitriles in t{'. the optical yield is markedly decreascd 7U7o).Therefore, I servesboth as a licz
qi
( R , R )- 1 ( 1 6 , 1 5 8 - 1 5 s ) .
i
OCH3
CHr
c6HscHo Asymmetric aromatic allqlation; binaphthyls.t The reaction of l-naphthyllithium with a naphthylimine (2) catalyzed by I provides 3, which is hydrolyzed (H2O' CFTCOOH, NazSO+),with recovery of 1, to the aldehyde 4 in 85% ee. The stereochemistry can be improved by use of a bulky R group in 2.
+
BTZnCHfN
K. Soai. Y. Hirose. and S. Sakata.Tetralx$
(S)-(+)- or (R)-(-)-Diphenyl(1-methyl-2-pyrrolidinyl)methanol (1)
c ,.rrrl diazaborolidineI o.. ,,t (S)-t-butyl thiopron: j-.tmino acid esters 4,
cH.?
liu't
r)r.4. r)v'\/ :-a
l3t
(R,R)-1 c6H5cH3,-45'
Li 2,R=c-Q.11" 3
(s.s)-1, N(C2Hd3 hexane,-78' StHsCHs,
85% I H.o.
t -
'la
R
,
O
L-J
c,H{
CH"
5, 90% ee 4 ,gso/oee
. i-
-r: 5lu7 (1991).
v.
6
rn5-j ( 1992).
' M. Shindo, K. Koga, and K. Tomioka, Am. Soc., ll4, g732 ,lg92).
(S)-(+)- or (R)-(-)-Diphenyt(l-methyt-2-pyrrotidinyt)methanot (l). Enantioselective cyanomethylation.l cyanomethylzinc bromide, prepared by reaction of BrcH2cN with znlcu, adds to aryl aldehydesin rhe presenceof (S)-l (l cquiv.) to give B-hydroxy nitriles in 87-93vo ee. If only 0.3 mol% of (S)-l is present the optical yield is markedly decreased(in the case of C6HsCHO ec falls from 93 to 787o).Therefore, I servesboth as a lieand and a catalvst.
poHs Ar,\-cuHu (s)-1 \Nl, bH
' r 8 ' 15 9 ) .
I
CHs ( s )- 1
c6H5cHo :! :. :r()nof l-naphthyllithium r.:'rih is hydrolyzed(H2O' d- { in 85Va ee. The stereon l
+
BTZnCH2CN
T H F ,- 1 3 "
*
RCH(OH)CH2CN (S), 93%ee
K. Soai, Y. Hirose, and S. Sakata, Tetrahed.ronAsymmetry, 3, 6j7 (1gg2)
r32
Diphenylsilane/AIBN
Diphenylsilane/AlBN. into alkenes by Alkenes from vic-diols.r Bisldithiocarbonates) can be converted areequally initiator an and Diphenylsilane (8,499). reactionwith tributyltin hydride/AIBN particularly gives reaction radical This effective and avoid use of toxic tin compounds. high yields in reactionsof nucleosidederivatives' 1 ) N a H ;C S 2 ,C H 3 l
R3Siq
2) (c6H5)2siH2,AIBN 80- 1100 > 911"
\)-e"s" Hd
R35iq \)-4"""
OH
lD.H.R.Barton,D.O'Jang,andJ.Cs.Jaszberenyi,TetrahedronLetters,32,2569(1991').
Enzymes. The earliest use of enzYmesr common bakers' Yeast (Sacc/rarv in the wine industrY.Although tt
by fermenting Yeastto benzvl-l' reactionwas viewed as a challcq as the biochemical one. Indeed t reportedin Organic Synlfteses.Ho
ways as shown bY two exhaust reports, more examPles from I cnantiomericexcessis at least)9
tbr preparation of enantiomerice The recent decisions of the Fo cnantiomericdrugs ratherthan to
ro use of enzymesor other as1Bakers' Yeast is used almo h-v a dehydrogenasewhich usrl
reductions,highest enantiosele ketones.B-Keto estersare also p-keto acids can also be reducc Yeast contains a varielv of cnzyme is preferable' These art and liPases.I lvases,isomerases, Purified reductasesusuallYrequ can be used as biocatalYsts.A
available.5These reductionscar The most widelY used enzrr nitrilases,ProbablYbecausetk commerciallY.TheY are Partic Esterasescan also .r'nthesis.s'e
Enzyme-catalYzedtransesterific and diols.lo A promisingnew areaof enz rcdox systemsthat are not PY-ri benzylviologen(commerciallr I
eas,formate, or carbon monorr sourceis a 2-enoatereductase.c
-.1:rbc convertedinto alkenesby - . ..rlanc and an initiator areequally ry': l' - :.'Jical reactiongives particularly tt..
>
::..
Enzymes. The earliestuse of enzymesas reagentsfor enantioselectivereactionsemployed the common bakers' yeast (Saccharomycescerevisiae), which had been used for centuries
R 3 Soi
\y
Base
. 'n Ldters, 32,2569 (1991).
in the wine industry. Although it was known in 1966 that benzaldehyde-l-dis reduced by fermenting yeast to benzyl-r-d alcohol in looro ee, this example of an asymmetric reaction was viewed as a challenge to chemists to develop chemical systems as efficient as the biochemical one. Indeed only two examplesr of enzymatic reactionshave been reported in Orgonic Syntheses.Ho'vre\er, Jeast reductionshave proved usetu) in numerous ways as shown by two exhaustivereports listing nearly 700 references.2 Since these reports' more examples from 1988 through 1991 have been listed if the reported enantiomericexcessis atleast)95Vo.3 This last review coversthe general useof enzymes for preparation of enantiomerically pure compounds (gg0 references). The recentdecisionsof the Food and Drug Administrationto give preference to single enantiomericdrugs ratherthan to the racemateswill undoubtedlyprovide further impetus to use of enzymesor other asymmetricreactionsin drug design.a Bakers' yeast is used armost excrusivery for reduction, principalry of ketones, by a dehydrogenasewhich usually follows the prelog-cram rule. As with chemical reductions,highest enantioselectivityobtains with aromatic aldehydes and aryr methyl ketones.p-Keto estersare arso reduced with high eanantioserectivity by yeast. some B-keto acids can also be reducedefficiently to (R)_B_hydroxyacids. Yeast contains a variety of enzymes, and in some cases use of a single purified enzyme is preferable.These are divided into oxidoreductases, transferases, hydrolases, lyases'isomerases, and lipases.Many of theseare commerciallyavailable(but expensive). Purified reductasesusually require expensivecofactors.In addition individual microbes can be used as biocatalysts.A general review of microbial asymmetric reductionsis available.5These reductionscan be the oppositeof those of yeast. The most widely used enzymesare the hydrolytic enzymes: lipases,proteases,and nitrilases,probably becausethese enzymes do not require cofactors and are available commercially. They are particularly useful for resolution of esters,6,? and for organic synthesis.8'e Esterasescan also catalyzeesterificationif the water concentration is low. Enzyme-catalyzed transesterification can be used for resolution of secondary alcohols and diols.ro A promisingnew areaof enzymaticreactionsis that of anaerobes. Theseorganismsuse redox systemsthat are not pyridine nucleotidedependent,but can use methylvirorogenor benzylviologen(commerciallyavailable)as mediators.Erectron donorscan be hydrogen qas' formate, or carbon monoxide rather than glucose.rl The first new enzyme from this sourceis a 2-enoatereductase,effected with stereospeclfic trans-addition of hydroeen. An
134
EPhedrine
additionaldoubleortriplebondinconjunctionisnotreduced.2-Enalsalealsoreduced, butreversibly.A2-hydroxycarboxylateviologenoxidoreductamhasalsobeenidentified. Carboxylicacidreductase.f,o,nunu",obescanreduceacidstoaldehydesinthepresence of methYlviologen. Anothernewdevelopmentinenzymaticreactionsistheuseofmonoclonalantibodies ascatalysts.Theseantibodiesshowregio-andstereoselectivity'substratespecificity,and rateacceleration.Hilvertl2hasdiscussedthreedifferentreactionsthatalecatalyzedby theseantibodies:decarboxylation,Diels-A|derreactions,andClaisenrearrangements. possibilities' This catalysis is a new field with tremendous (1990). 1 (1985);K. Mori andH. Mori, ibid.,68,56 1D. Seebach et al., organic Synthesis,63' (1991)' 49 9f' Rev'' 2S. Servin,Synthesis, I (1;qi; R. CsukandB.I' Glanzer'Chem' 1071(1992)' 3 E. Santaniello,P. Ferraboschi, P. Grisenti,and A. Manzocchi,chem' Rev',92' 4 "Chiral Drugs,"C&EN, Sept' 28, 46 (1992)' 5 H. Yamadaand S' Shimizu'Angew'Chem'Int' Ed'' 27' 622 (1988)' 6C.-S.Ch"nandC.J.Seh,Angew'Chem'lnt'Ed'28'695-707(1989)' 1047(1991)' 7 W. Baland,C. Frescsel, and M' Lorenz'Synthesis' 8A.I.M.Janssen,A.J.H.Khunder,andB.Zwanenburg,Tetrahedron,47,4513,7409,7645(|991). PureAppl. R. Sumayev,and M. Schneider, 9U. Ader, P' Andersch'M. Bergu'U. Goesgens, Chem.,64, 1164(1'992)' '753(1990)' r0H. G. Leuenberger,PureAppl' Chem'' 62' (1992)' rrH. Simon,PureAppl' Chem',64' 1181 12D.Hilvert,PureAppl' Chem',64' 1103(1992)'
l' I J987o ee.
(2S,4R)-1 + (CH3)2Zn Preliminary results indicate r.\. ?:-.- .,\ a chiral ligand for dibutYl- , .nhcdrincwith HMPA. Highest r.: I l()r onc equiv. of the cuprate
?3ot"'.
\efrt'B.l
o : , - . : :l l M o r | i b i d . , 6 8 , 5 6 ( 1 9 9 0 ) . '. r , .r Rt't., 91,49 (1991). r, - r hL'm.Rev., 92, lO71 (1992).
C6H5 COOC2H5
ether 0'
t
l
(^f^t"' HO
Bzl 2
*
c6Hscooc2Hs t l "'ctts
(\N/ HO Bzl
86:14
I H2,PdlC
{ cooc2H5 HrN^cH. (R)-3
h
I C. Andrbs,A. Gonz6lez, M. A. Salvado,and S. Garcia-Granda, A. P6rez-Encabo, R. Pedrosa, Letters,33, 4743 (1992). F. G6mez-Beltrin,Tetrahedron
I t r - - ,.clcctivity can vary from 0 to
ligandshave a : : , : -riral phosphorus tlr .
rq9l).
Ethyl (S)-lactate. Chiral sulfuxides.l These have been prepared by a Sharpless-type asymmetric oxidationof sulfides(13,53),but this route is only efficient for preparationof aryl methyl sulfoxides(ee up to 92-96Vo). A more generalroute involves reactionof a pure chiral
(E)-Ethylidenecyclopmpanone
136
ketal
cyclic sulfite (2) with organometallicreagents.It is particularlyuseful in the caseof the sulfite2, preparedas shown from ethyl (S)-lactate.The reactionof 2 with an alkyllithium
cH3 ,cH3 ^ oxo *
cH1;lrocttr
^J
->
2c6H5Mscr "tt1r"utu >
C6H3C>+ 60'
8ar
soct2,N(c2H5)s
,J rd'cut,
\
cHcoocH3 cHcoocH3
CHs 50% overall
cH3(
1
1
CHe poHs *C^H.
d.'s-.b l"o 'tr"nr-z
CHs
,CoHs cH3Mst ,K"utu -HO p 7O/" CH"-S.
-
6!
"'..
n-OctMgBr, A
-'100o/o
CHo
./
n-Oct
- s'o l
+1
(R)-4(100%ee)
cH3od
cts -2460 |
1 ) n - O c tM g B r( 6 1 % ) 2) cH3Msl (-100%)
|
I n-Oct. ,CH3
:csult in productswith four chiral ccnta
+ 1
.('.o (S)-4(100%ee)
or alkyl Grignard reagentproceedswith marked regioslectivityand complete Inverslon of sulfur to provide a sulfinate(3), which on reactionwith a secondorganometallicgives a chiral sulfoxide (4) in quantitativeyield togetherwith the chiral auxiliary diol l. The method is particularly useful in preparationof alkyl l-butyl sulfoxides since t-BuMgCl reactswith trans-2with a selectivity of 95:5 in contrastto that of CHjMgCl (80:20). I F. Rebiere, O. Samuel,L. Ricard,and H. B. Kagan,J. Org., 56,5991(1991).
(E)-Ethylidenecyclopropanoneketal (l). [3+2]Cycloaddilion to alkenes.r The ketal I when heated (60-100") can undergo regio- and endo-selective[3 + 2]cycloadditionto electron-deficientalkenes.Since hydrolysis of the adduct proceedswith >90% stereoselectivity,this cycloaddition can
{r S. Ejeri,S. Yamago,and E. Nakamura.
(E)-Ethylidenecyclopmpanone
-:;lrrlv usefulin the caseof the ,.rion of 2 with an alkYllithium
F ft
CHs ,CHs
.1
o--.-o + cHcoocH3 cHcoocH3 /\
->
i.
SOC|2, N(C2Hs)3
CHg -rr
50% overall 1
| "oo", "ro I .r l^Q'
'
l0oo
CH3 ,n-Oct
..t"'o
?"
+1
(R)-4(100%ee)
O-\--OCH29CH20H l
l
cH" I z\--cHs \ / cH3o2c'
borcH, >9:1
rcsult in products with four chiral centers with high stereocontrol i S. Ejeri, S. Yamago, and E. Nakamura,Am. Soc., 114,8707 (1992)'
t\f . i
lr
i
..;itrvitv and completeinverston "r .r \cc()ndorganometallic gives r rhc chiral auxiliarYdiol t. The ''utrl sulfoxidessince l-BuMgCl -' :Lrthat of CHsMgCl (80:20). s 6 5 e 9 l( 1 9 9 1 ) .
il I .\ hcn heated(60-100') can unrlcctron-deficientalkenes.Since u. -ricctivity, this cycloadditioncan re'-
ketal
137
Ferric chloride. Perylenequinone(2).t
A novel route to this quinone (2) involves double coupling (1), prepared as shown, by treatment with FeCl3 of the 5-bromo-1,2-napthoquinone
o /'\/-\
t
l
l
equiv.) is most satisfactory,and CH.1NO; rs tl
OAICb
1 ) S e O z ,H O A o( 7 1 " / . ) 2) NBS, H2SO4(41%)
l
This is a fairly generalanomerization.tetn are labile to FeCl3, but reactionsare fa^steru with furanosides.The reaction of the glrcos temperatureand is complete in 15 minutc'st.r Oxidative coupling of ArOAlC12.' Otxt plicated mixtures, but oxidative coupling of , route to hydroxylatedbi- and tetraaryls.The s phenolswith AlCl3 in CHTNOz and need nt{ I
coocH3 coocH3
A
2 | \/
FeCl3 CH3N02,25'
I
I
CHg
CHg
l0ol. FeCl3/CH3CN 25' 910k
FeCl3 CHsNOz,80'
cH3o cH30
CHs
ocH3o 2 in anhydrousacetonitrileat 25". Anomerization catalJst.2 In the courseof debenzylation/4-methoxycinnamoylation of the a-glycopranosideI promotedby FeClj, Nakanishie/ a/. observedthat the anomeric p-methoxyl group is anomerizedto give a-glycoside 2 (a/B : 95:5).
BzlO
ocH3 BzlO
"'oBzl
1) FeCl3 AgOTf 2) 4-CH3OCinnCl,
OR t
^
vo)*...ocH3
t l RO/Y,,OR
OR 2, R = CHzOCinn
tf$. -15I I Z. Diwu and J.W. lnwn, Tetrahed762, \. Ikemoto, O.K. Kim, L.-C.l-o, V. Satlanan ! etters,33, 4295(1992). (i. Sartori,R. Maggi,F. Bigi, A. Arienti.G (est ,r1r.t3 (1992).
lluorosilicic acid, H2SiF6. Desilylation.l This acid is less acidic rh jffcct on acid-labileprotectinggroups.A funL ,i r-butyldimethylsilylethers in the Prcs.'nct .rhers. The selectivity of HzSiFr,can be enh :ficctive than DMAP). The cleavageis effccr .ifter one hour.
RL t A. S. Pilcher,D. K. Hill, S.J. Shimshock. r 1992).
Fluomsilicic
rr- - . i 2) involvesdoublecoupling s . rn. hy treatment with FeCl3
acid
139
This is a fairly generalanomerization.tetracetyl,Acetonidesand benzylidine acetals are labile to FeCl:, but reactionsare faster with acetyl derivatives.The method fails with furanosides. The reaction of the glycoside I is carried out in CHzClz at room temperatureand is complete in 15 minutes to 5 hours. oxidative coupling of phenols results in comoxidative coupling of AroAlcl2.3 plicated mixtures, but oxidative coupling of dichloroaluminum phenolatesis a useful route to hydroxylated bi- and tetraaryls. The starting material is obtained by reaction of phenolswith AlCl3 in CH:NOz and need not be isolated.Of severaloxidants,FeCl3 (1 equiv.) is most satisfactory,and CH3NOz is the preferredsolvent.
ocH3o
"-'-)-'-ro
QHs FeCl3 cH3N02, 25'
i l l )\z\/coocH3
h:
Br CHs
rsomers
+ 98:2
lFl FeCl3 cH3N02, 80'
coocH3 'coocH3
+
tsomers
98:2
CH
r-- r .,:r()n-l-methoxycinnamoylation thatthe anomeric .',i1.rrhserved n:. N l , c - 1 , (Br : 9 5 : 5 ) . OR
: ! -
\,.o{'.ocH3 | | eo/'{""oR t
l
I OR 2, R = CH2OCinn
' Z. Diwu and J. W. Lown, Tetrahedron, 48, 45 (1992). I N. fkemoto,O. K. Kim, L.-C. l-o, V. Satyanarayana, M. Chang,and K. Nakanishi,Tetrahedron Letters,33, 4295 (1992). t 48, G. Sartori,R. Maggi,F. Bigi, A. Arienti,G. Casnati,G. Bocelli,and G. Mori, Tetrahedron, e483 (1992).
F-luorosilicicacid, H2SiF6. Desilylatian.t This acid is less acidic than HF, and can effect desilylationwithout c-ffecton acid-labileprotectinggroups.A further advantageis that it can effect desilylation of r-butyldimethylsilylethers in the presenceof l-butyldiphenylsilylor triisopropylsilyl cthers.The selectivity of HzSiFe can be enhancedby addition of triethylamine (more cffectivethan DMAP). The cleavageis effectedin CH:CN at 0" and is usually complete after one hour. J. Org.,57,2492 andP. DeShong, R.E. Waltermire, D.K. Hill, S.J. Shimshock, A.S. Pilcher, \t992).
+ (CH3(CH2)aCO)20
Gallium(Il) chloride, GaCl' GaCl: (Ga2Cla)' ReductiveFriedel.Craftsreaction.|Reactionofaniso|ewithGazCla(2equiv')and anaromaticaldehydeinCS2atloomtempelatureresultsindiphenylmethanes.Similar reaction involves the reducing resultsobtain with ketonesand aliphatic aldehydes.This ability of GaCl and the Lewis acid activity of GaClr'
'ffi cHo Ga2Cl4 cs2,25"
,\
i l l
cH,o)J
47v"
Y
+
11 ,"\a/\/\
i
OCHs
\2\ocHs 89 .
l
t
i
l
\z\ocn\Z\o*r.
T. Ohno,T' Nishimura'S S T. Mukaiyama, : T. Harada,T. Ohno,S. Kobayashi, andT I
Grignard reagents. Modified Grignard reagents, RUg) hv reactionof RLi and Mgtz [L:OSO: ligand can exert a marked effect in ad rcactsexclusivelywith an aldehydein tl .rldehydein high selectivity (equationl
l
o (r)
c6H5cHo *
"rru^
CHsQ
?""'
U
cHo ..\
l
l
33' 6357 I y. Hashimoto, K. Hirata, N. Kihara, M. Hasegawa, and K. Saigo, Tetrahedron Letters'
(1ee2). Gallium(IlD chloride-Silver perchlorate' Friedel.Craftsacylation.ThisreactionisgenerallyeffectedwithAlClr'buta stoichiometricamountisrequired.SinceacombinationofLewisacidsissometimes et al.t have examined the reactivity more effective than a single t-ewis acid, Mukaiyama AgCloa and report that the combination of of several lrwis acids in combination with AgClOawithGaCl:,AlCl3,orBCl3resultsinacatalystthatcaneffectFriedel-Crafts when Agcloa and Gacl3 are present uilution in good yield. Highest yields are obtained presumablyGacl(clo+)2, and high is in the ratio of 2:1. The altual catalytic species catalyst'2 yields are obtained by use of I0 mol 7a of this
c6H5YcHo
cH3MgL
CHs
L=Cl'Br'l L=OTs L=OAc
The ligand has a marked effcc :'chiral aldehydes(equationIl). lt can .:lohexanones(equationIII).
Grignard
+ (CHg(CHz)rCO)zO
reagents
?"r'
G a C l 3/ A g C l O 4( l : 2 ) cH2cl2,35'
,t\
VI
9'1"/"
oA(cHr)o CHs .{,lc with GazClq(2 equiv') and Similar . rn diphenYlmethanes' rc.rctioninvolvesthe reducing
' : (
ocH3
hC
Aq
. 't1 -.,-\.'\. l
+ t
i
I T. Mukaiyama, Chem.Letters,7059(1991). S. Suda,andS. Kobayashi, T. Ohno,T. Nishimura, : T. Harada,T. Ohno,S. Kobayashi, 1216(1991)' Synthesis, andT. Mukaiyama,
Grignard reagents. Modifi.ed Grignard reagents, RMgL.t These Grignard reagents can be prepared bv reactionof RLi and MgL, [L:OSO2CFr, OSO2CHj, OCOCHI, OCOC(CH3)r]' The ligand can exert a marked effect in addition to carbonyls.Thus cHrMgococ(cHl)l rcactsexclusively with an aldehydein the presenceof ketone to form the adduct of the .rldehydein high selectivity (equationI).
l
l
o
l
-ocn\Z\ocn,
(l)
C6H5CHO
+
CH3MgOcoC(CH3)3
cuHrAcH.
- n3v,
?*. c.HuAoH
cH3lcH3
*
cu"u^o"
99:1
li
\
\.irtl(). TetrahedronLetters' 33' 6351
c6H5YcHo
CH3MgL
"utuyo"".
i ' , : , . 1' t . l
-.
U6nS -- -,,\^,
CHs
CHs
but a ; .,':-i.rllv cffectedwith AlCl3' sometimes is ni ::rr,nof kwis acids a" t . : ,tl.r haveexaminedthe reactivity of 1"o. .rntl report that the combination Friedel-Crafu : - :i.,lrst that can effect are presenl tx.: .\ tcn AgClOa and GaCl3 '-i:urritbly GaCl(ClOa)2'and high 1 -
9H :
OH I
L = Cl, Br, |
8Oo/"
70:30
L = OTs
76/o
92:B
L = OAc
83o/"
9 1: 9
I CHs
, \.rr3
The ligand has a marked effect on the reaction of Grignard reagcnts with :.chiral aldehydes(equationII). It can also affect the addition of reagentsto substituted .',:krhexanones(equationIII).
Grignard
reagents
_o (llr)(cfthc-H OH
?ut' (cH3)3c=JA?oH
1cH.;.c-AfcoHs
lM.T.
C6H5MgBr
94o/o
49:51
C6H5MgOTf
87"/o
73:27
C6H5MgOTs
9O/"
85:15
l. l, 1,2,3,3,3-Heptamethyltrisilane,( CH t, I I Preparation. Radical reductions.2 This silane is I :cduction of substrateswhen the produo r tcneral procedureit is used in combinatioo ,r 75-90'. It is effectivefor reductionof ha
\1. Kumada,M. Ishikawa,andS. Maeda../ () : t'. Chatgilialoglu, A. Guerrini,and M. Luc:ru
Reetz, N. Harmat, and R. Mahrwald, Angew Chem.Int. Ed., 31,342 (1992).
Hexamethylditin.
[4+IlRadical annelation.t Inadiatro 'rJone 1, phenyl isocyanide(5 equiv.).ari :: tl0'results in the tetracycle2 in -l{X? 1
"
z^r)
o tl +
C6H5NC
,r/\-/
[ .s
'\-1
o
| \z\')'-("8o%' Yields are generally t"t^i" "Jtoride'
aceticor more effectivethan
l -Hvdroxy-3-isothiocyanatotetrabut]l 'Acetalizltion'' Distannoxanesof activateboth d can they 115,89)because 1 is found Of a number of stannoxanes' ethvlerx with ketones ,lf aldehydesand usuallr t which of cvclic a,B-enones'
andP'Nantka-NT:':lt'#'ri8;ilil?? rR.Balicki, L.Kaczmarek, A: "?:),:.,";r;,iri. P.A Giguere' and 26..Lu, E.w. Hughes. i' euti't.'i'andP' Nantka-NamrrsKr' t;. ;;;;;"'ki'
tonr,tuntl.
(l)'
o
(R,R) or (S.,S)-6'6'-(1-Hydroxy'2'2-dimethylpropyl)-2'2l-bipyridine a/oof this of 5 mol Preparatton' . . ,: -.L,.r-;-" n RCHO.2 ln the presence
.,':iii*;,;ff:;;::I::if#iltffiil (equationl)'
ll
a\
'r ardehvdes 'oi'i.,"*'0"varie'v
+ HOCH{
\-/
with high enantiosetectivity
o
c!-lell
-^j,'\ t t
C(CHs)s CoHs
0)
C(CHg)s
(cH3)3c
OH (R)-2
(R,R)- 1
1, toluene -25 -> 00
Zn(C2H5)2
80 - 97%
,
RCHO
\..e"
gf-c2H5
2',/-"r/
o
HOCFtPTT
l
'1 I'iitrl. Sincea cycloalkene 5. i:r rr\ crall processprobably b. l.l-diol or oxidizedfurther ir::!:'.-bv this reactionin 8O7o r:.lJ. B
149
l-Hydroxy-3-isothiocyanatotetrabutyldistannoxane
Itnt
, . , . 1( 1 9 9 2 ) .
Surprisingly,the simple pyridine (R)-2 is almost as effective as (R,R)-1 as the chiral catalyst.Moreover it can show high asymmetricamplification.Thus use of R-2 with an ee of 14Vocan provide an adduct with 87% ee. Enantioselective addition of R2Zn to enones.s This conjugate addition of R2Zn to chalconescan be effected by catalysiswith Ni(acac)2-(S,S)-1 in the ratio l:20. In this caseuse of aceto-or propionitrile as solvent is essential.In this reaction,the pyrid-
o
CzHsQ
Ni(acac)2,(S,S)-1 (C2H5)22n, CH3CN
cuHu4JcuHu
cunu,,,+cuH,
(R), 72o/oee n :. ,\ croxidationto a sulfone, ) " : l ( \ o f H 2 O 2w i t h u r e ai n rl. r'l and provides sulfoxides
ine (R)-2 is more effective than (S,S)-1 as the chiral ligand. Thus use of Ni(acac)2(R)-2 producesthe same adduct in 827o ee. Asymmetric amplificationwith (R)-2 was also observedin this reaction.
o : . : 1),i c e . n,--\ ()r of N-heteroaromatic r- .rrllt the HzOz/ureaadduct :r :J cf'fectivethan acetic or
I C. Bolm, M. Ewald,M. Felder,andG. Schlingloff,Ber.,125,1''l'69 (1992). rC. Bolm, G. Schlingloff,andK. Harms,Ber., 125, 1191(1992). I C. Bolm, M. Ewald,and M. Felder,Ber., 125,1205(1992). (1). l-Hydroxy-3-isothiocyanatotetrabutyldistannoxane,HOSn(Bu)2OSn(Bu)2NCS Acetalizatian,r Distannoxanesof this type are useful catalysts for esterification ( 15,89)becausethey can activateboth alcoholsand carbonylgroupson the sametemplate. Of a number of stannoxanes,I is found to be the most efficient catalystfor acetalization of aldehydesand ketoneswith ethyleneglycol. In particularit can promoteacetalization
,._). l:.: , .. r1992). ;
of cyclic a,B-enones,which usuallyproceedsin low yield. l - h i p r r i d i n e( l ) . tl^- :-:.\cnceof 5 mol % of this : , * idc variety of aldehYdes
1-l
o
A
(-j
001 1 X
+ HocH2cH2oH ""L
(-l
o
CHsll
^
z-\ I
OH
68/"
i-1-'-2-.....-,>
^\*,/\-.,.C(CHs)g
''
a--.-H\ l l l
+
( 1 0e q . ) HOCH2CH2OH
\--O
+
1
(R) 2
\..et nG-czHs
93/"
150
N-HYdmxYurethane
1 J. Otera, N. Dan-oh, and H' Nozaki, Tetrahedron' 48' 1449 (1992)'
14, 179- 180; 16' l7 9' [Hydroxy(tosyloxy)iodolbenzene, is usually conductedin refluxing a-Tosylorylation of ketones'\ This reaction acetonitrile.Therateofthereactionismarkedlyincreasedbysonication.Thusitcan beconductedundersonlcationat55.in10-30minutes.Thisversioncanbeusedto evenalicyclicketones' tosyloxylate
,OBzl BzlO-\YOr -O- -COOCzHs BzIOW--N' BzlO H 2
HMPA (82%) 1) NaH, (C2H5)2O, 2) NaOH{s), CH3OH (80%)
B'C Bz
I D. Yang, S.-H. Kim, and D. Kahne,Az. -kr
C6H5|(OH)OTS cH3cN.((((
O ii
A CHe-
v
-CHs
91o/"
O
O
A ..cHs+ rso=.,\.cH3 CHs- Y 5:1 611
o
a\ t
1
OTs
l
r A . T u n c a y ,J . A . D u s t m a n ,G . F i s h e r ,c . I . T u n c a y ,a n d K , S . S u s r i c k , T e r r a h e d r o n L e t t e r s , S 3 ,
7647 (r9e2).
(1)' Available from Aldrich' N-Hydroxyurethane, HONHCOOC2H5 N_oLinkedglycosides.|Thetrisaccharidegroupofseveralpotentantitumor linkage. A general method for stereoselective antibiotics contains an unusual N-o The N-hydroxyurethaneas the key reagent' synthesis of such saccharidesemploys selectively occurs glycosylation that group so carboethoxy group deactivatesthe nitrogen withthehydroxylgroup,butitfacilitatesdeprotonationofthenitrogentopermit s u b s e q u e n t S p 2 d i s p l a c e m e n t w i t h i n v e r s i o n . T h e r e q u i s i t e g l y c o s y l u r e t h aof n e2s s u c h a s 2 glycosyl.sulfoxidewith 1' Deprotonation can be prepareddirectly by reactionof a ( N a H ) p r o v i d e s a n a n i o n o n n i t , o g " n t h a t r e a c t s w i t h a t r i f l a t e ( 3 ) w i t h i n v e- r s 25" i o n ito nhigh by NaOH (solid) in CH3OH at 0" yield. The coupled product is def,rotected disaccharide4' provide thc N-O
I
N-Hydmxyurethane
tt9 qt.
,oBzl
ezo-\vQ
o_N-cooczHs
BzlO--r*/ BzlO
) tr.-.,11\conducted in refluxing q J \r sonication.Thus it can r I:r. versioncan be used to
H 2
1) NaH, (C2H5)2O, HMPA (82%) 2) NaOH1el, CH3OH (80%)
o
tl )H, - TsO--.../A-..-,-CH3 . ' 5 1
ls
\
Letters, 33, : -trck. Tetrahed,ron
i: ". \ldrich. o-:- ,l scveral potent antitumor nr:, rncthodfor stereoselective rr-:'- its the keY reagent.The 6 s. .., r:r lationoccursselectively l:: - ,)l thc nitrogen to Permit suchas 2 r.:'- :lrcosyl urethanes of 2 o\ .:, \\ ith l. DeProtonation high in r:.:' ,:r (3) with inversion s :, rn CHrOH at 0' * 25' to
\-\-O
BzloS
Btlobcu. 3
BzlO
BzlO
r D . Y a n g , S . - H . K i m , a n d D Kahne, Am. Soc., ll3, 471.5 (1.991);Idem, in press
l5l
BocO
cHrZ-\')'-"-'
r
CHs
.a
1
water or Indium. 1 indium is stable to boiling Unlike most metals' a water" in AllYlntion 25' with no need for aldehvdesin water at effecl il;;;;";;; can alcohol. Indium promotor'
o tl
o^o t
l
-y' r^ -(cxz lcH2" -\
iH. H2O,25"
c6H5cHo * ,rNc^'
In, -G**
2a
?t
c6n5*cH2
lz, CHgCN'-20' lBr, C6H5CH3'-80-85'
OH OH
*
cuHuAcno
erNcH,
-a*
cuau/\1,-'-zcH' OH = 67:33) @Yn/anti
Thereactionwhenextendedtoacrylatesprovideshydroxyacrylicesters'whichare precursorsto methylene TJactones'
The generallY higher selcorr homoallylic carbonates. lJ.J.-w. Duan,P.A. Sprenger. and I
Iodine/Pyridine. a-Iodination of cYclulLcz cquiv.) dissolved in PYridineCO
oH 9Hz
. r,-y::;. c6H5cHo
1 C.J. Li and T.H.
rHl
"uruScoocH3
32"1.017 (1991)' Chan, Tetrahedron Letters'
"^t"ir#,iii**[)]i;t'"rl;""'"'
ncO,,,.O
or the rhe conversion ol no\latttr.carbonates''
atNtemperatures c a r b o n a t e l t o 2 h a s n ' O i t i " * i f y b e erBr n ein f f etoluene, c t e d * uparticularly it'inCHrC a t - 2 0 ' ' l t c aofn b e with ;.;;i, higher carriedout with -80-85".
C . R . J o h n s o n ,J . P . A d a m s . M P Ukokovi6, Tetrahedron Leuers. 33
Iodine/Pyridine
153
BocO I
Cuzr'"f'VOgzt CHs 1 m . rtable to boiling water or : .ir 25" with no need for a l.l
o tl o^o l
o,
l
o tl
l -\ -\ -(CHz)zOBzl + IcH2-'-\a-'\ lCHz' Y
OH )"'r.
o r
(cH2)20Bzl
CHs
CHs
2a
2p
*CHz t2,cH3cN,-20" -80-85" lBr,C6H5CH3,
OH
7g%
5.7:1
8oo/o
14.9:1
I
- ,, )--,r'----ZCHz -
l
OH = 67:33) \syn/anti
The generally higher selectivity of IBr was observed with a number of other homoallylic carbonates. I J.J.-W.Duan,P.A. Sprenger, andA. B. Smith,III, Tetrahedron Leuers,33, 6439(lgg2).
hl.:- ,\\ acrylic esters,which are
oH
c.,i.
Iodine/Pyridine. a-Iodination of cycloalkenones.t This reaction can be effected with 12 (1-4 equiv.)dissolvedin pyridine/CCl+(1:1) at O - 25".
CHe
o
'-l\AcoocH3 A
(A"r.
nco,,, cro trnalt'r.i The conversion of the I ::: ('HICN at -2O".It can be n. :.lrricularly at temperaturesof
o t2,pytccta)-'.'
1*-
t.*CHsr l
77o/"
nco,,, 1^7o
a,
C . R . J o h n s o n ,J . P . A d a m s , M . P . B r a u n , C . B . W . S e n a n a y a k aP, . M . W o v k u l i c h , a n d M . R . Ukokovid, Tetrahedron Letters, 33, 917 (1992).
154
Iodine-Silvertrifluoroacehte
'u':;i,:';;:"i";X:;;;?:;,;:li:,:ihtdroruransLip**1'hasprepared choice by a r' unor'u"shownthat
n'jJ"tr''""'il*t thefour isomers"r tr't
CHs 1,,CF3COOAg
"t')t)r
-l
\cH.
oH
/l
\ I
CHs
II c.nus"ct
\-
\r'=.t
l(
r\ ll
I
\Z^-r'i
4'1"/"
)-oLi
1
lr . . t . dengibsin(6) from the : : . :r:r()rL-none
rW. Wang and V. Snieckus,J. Org., 57, 424 (1992). 28. G6mez, E. Guiti6n, and L. Castedo, Synleu., 9o3 (1992).
. 5 Methylation and desilYlation with BCl3 provides6. - :-.rlkvlation
,1:.1
t
Lithium diisopropylamide/Butyllithium. (LDA) B-Lithio ketone enolates.r B-Stannyl ketones2such as I on deprotonation -78 to 0" are convertedinto to the enolate followed by LilSn exchangewith BuLi at the p-lithio ketone(Z)-enolatea. This speciesundergoesB-alkylation more readily than
coN(c2Hs)2
a-alkylation; B-alkylation followed by a-allylation is also possible.
OH TES Ol-Pr
FC
Lir. o--Li
0"
,-rr-v
t-BuMSnBu3
5
\
1) LDA, -78" 2) BuLi,-78'-
o tl
a
1
o r-euAlcHs)ocHs
1) n - C5H11Br n - C5H11Br
71"/"
a
2) cH2=cHcH2Br 700/o
o .rr\tcHs)scHg
\'-zcu,
{.c I I H. Nakahira,I. Ryu, M. Ikebe, N. Kambe, and N. Sonoda,Angew. Chem.Int. Ed.' 30' 1'77(1991) r I. Ryu, S. Murai, and N. Sonoda,J. Org., 51,2389 (1986).
a'i tll,'
rproach to the basic skeleton of ,'t rhc amide I to form 2, effected
Lithium perchlorate. [1,3]Sigmatropicrearrangementof allyl vinyl ethers.t Allylic vinyl ethersrearin diethyletherat 25'to homoallylicaldehydes. rangein 3M lithiumperchlorate
Lithium
Perrchlorate
cHa?
QBzl
cH.
cHo
* cnlvsn(cH3)3
LiClO4,ether 90"/.
HO'
r il-
,CH2CHO
CHs'l-OH
I
H
HO-
t
CHs'
-
H
\oH
CHa
l oAcH,
I
al t$ctt.
Aldol reaction of silyl enol ethcrs'' ketal I at 25' in the presenceof LiCIO' tUnder these conditions a chiral a-alkorr :
&::
psiR3 c6H5cHO +
cHz{
!
ocH3 ConjugateadditionoJ'o-silylketeneacetalstoenones.2Additionofl-methoxy-1(r-butyldimethylsilyloxy)cthylenetocyclohexenoneproceedsinlowyieldwhencatalyzed in 95% yield when catalyzedby 1'0 M by TiCla or TiCl+/Ti(O-i-fr;, Uut is effected LiClOa in diethYl ether'
osiR3
o
A
(A
* cHg
""ryOSi(f-Bu)Mez ocH3
LiClOa,Et2O
737"
U
CHs..--,.CHO : * 6azt
CHzl
/osiR3 ocH3 1
a\
s"rr"oocH3 osiR3
o .,\
1
I
*
"t."tYosi(t-Bu)Mez OC2H5
B7v"
\--\.".
cooc2Hs
to a-hydrory aldehydes'3 This reaction syn-Selectiveadtlition of allylstannanes (Ticla, MgBr2). It can also be effected by is usually effected with rcwjs acid catalysts use of 5 M LiCl4O in ether'
:helation control.
Substilution of allylic alcohok by s$ .ubstitution with 1-methoxy-1-(t-bunldtr Jicthyl ether.
Lithium
perchlorate
QBzl
QBzl -,\ -CHO * cHf'-,/Sn(cHs)gry CHs'
cn"r,\:,^"-r'cH, 0H ( 2 5: 1 )
,CH2CHO
CH Z"'-,.sn(CH3)3
Q--'"to H
t-BuMe2si6 6vort'r =cH, 6tr,tOlvt
f-BuMe2SiO
Aldol reaction of silyl enol ethers.a Benzaldehyde reacts with the silyl ketene ketal I at 25' in the presenceof Licloa (3 mol vo) to give the aldol 2 in 860/oyield. under these conditions a chiral a-alkoxy aldehyde reacts with I to give the aldol of
c '.:cocH3
'CHg
psiR3
* .t'1"r. c6H5cHo Additionof 1-methoxY-lr,,fr. \. r .. . ..r. in low yield when catalyzed i .:,lJ u'hen catalYzedbY 1'0 M
.
C . : ' J
: OBzl
a\
Uk#:oocH3 OSiRJ
o
+
frnel
/
PSiR3
ocH3
Liclo4' etnet.22o -
CHg
ocH3
: OBzl II I H F I V
ocH3
A
htd,r,trt' aldehydes.3 This reaction . \tillr-). It can also be effectedby
Resio
"urr/t-Ao"r.
1
W"t'cooc2Hs
-#*
1
CH3--.--.CHO
osiR3
Liclo4'
chelation control. substitution of allylic alcohols by silyt ketene acetals.s Allylic alcohols undergo (1) in 3M LiClOa in substitutionwith 1-methoxy-l-(r-butyldimethylsilyloxy)ethylene Jiethyl ether.
Lithiun pyrrolindobomhYdride
OH
I
ar \',
OSi-t-Bu(CH3)2
Licto4,o(c2Hs)2
I
I'
I ,2\
eo"/o
cH99:1)
o H o l t l c6n5lfc5H5 CHs
these alcohols (acetyl, benzyl). The high regioselectivity is attributed to magnesium chelation.The reactioncan also be used to generatesecondarydiols (last example).
(antilsyn = 98i2)
o' Hl ol
cuHrlt'cuH, CHs
9Bt
9t' ,t'\.'^\
l t t -crHu
1 "o, w
+
fan'o'
Mglz
cHg
\"rru
90"/"
(antilsyn= 99:1) (98:2)
(-. ri.
rhriumis highly dependenton ll,,*gv.r, the order of addition
J. Org.,56,5978 r ..\.Maryanoff,
P \ . ,lcoholswith MgI2 in toluene r l - . :c.c iodohydrins are reduced - .rpplicableto derivativesof rl
I C. Bonini,G. Righi,andG. Sotgiu,J. Org., 56, 6206(1991).
Manganese(Ill) acetate. The acetoacetateI undergoes cyclizaOxidative cyclization by addition to C=N.t '2H2O (0.5 in CH3COOH to give the ketone presence equiv.) tion in the of Mn(OAc)r (30-5OVo), of an intermediateimine. which is evidently formed by hydrolysis 2
o A,coocH3 -cH2cN |
,,,zcu" I
CHs 1
cH3ooc/ Mn(OAc)3
o>/K
/,--E\" 2
r76
Mercury(II)
acetate
This reaction can be used for synthesisof a decalindionesuch as 4 from 3, or for cyclization to cyclopentanones.
cH3cHo
CHr i l -
"r.\oot CH3 CH3
o ll
COOCH3 v -cH2cN
Mn(OAc)s +
|
13"/"
CeHs 3
'B.B. SniderandB.O. Buckman, J. Org.,57,322(1992).
Manganese(Ill) acetate-Copper(Il) acetate. Radical cyclization of polyenes.t Radical cyclization of the tetraunsaturatedBketo ester1 with MnO(OAc)7/Cu(OAc)2(2:l) affords the o-homo-5a-androstane2 with seven chiral centers in 3lVo yield.
CH3CHO +
cny'YooH I
z
CoHs Mn(OAc)3,Cu(OAc)2 ACOH,25' 3'1"/"
r P . A . Z o r e t i c ,X . W e n g ,M . L . C a s p a r a , n d D . G . D a v i s , T e t r a h e d r o n L e t t e r s , 3 2 , 4 8 1(91 9 9 1 ) .
Mercury(Il) acetate (2) can be preparedby reactionof hemiperoxy1,2,4-Trioxanes. 1,2,4-Trioxanes acetals(L) with Hg(OAc)2(1 equiv.) catalyzedby HClOa.This route can show high Thus the trioxane3 has the chair conformationwith all three diastereoselectivity.
substituentsequatorial. I A. J. BloodworthandN. A. Tallant.J. ('..s ('rk!.
Manganese(Il) acetate
,-J ^.tr,,nc such as 4 from 3, or for
OH
cH3cHo
CH, i l -
"t,\oot
t
,fr.\o H
l
l
cH.
-
1
cH3 cH3 1
l I 42o/^ -- | +
I CzHs 4
rYHs1on"1, 2)NaBH4 CH.
I ' o^o cHs>tr- _o
CHe' X cH3 cH3 2
pl:.',:i,,n of the tetraunsaturated lr'-- :r-homo-5a-androsta 2 nwei t h
CH"
cH3cHo* "rrzYo CoHs
I ' o^o
1)CF3COOH 2) Hg(OAc)2
O"Ornarr\6 CoHs uo-ru"r. | *"""o { CH. I
'
oi{o t - , 1 cH"-*do - t CoHs
. ,' n L e t t e r s 3 , 2, 4819 (1991).
3 (e,e,e >97o/o)
rr,-..i br reactionof hemiperoxyl{t t t- This route can show high ci : ' .()nformation with all three
"
"t.\o
cH3 cH3
coocH" " *.J-.\
cH, o
cF3cooH
substituentsequatorial. ' A. J. Bfoodworthand N. A. Tallant,J. C. S. Chem.Comm.,428(1.992).
178
l-Mesityl-2,2,2-trifluomethanol
Mercury(Il) trifloummethanesulfonate-N,N-Dimethylaniline' Hg(OTflr'C6H5N(CH3)2 0), 12, 307. polyene cyclizations.l This reagent (1) is particularly useful for cyclization of polyenes containing various oxygenated groups that can function as terminating groups' In this case cyclization occurs on oxygen rather than carbon, as observed with kwis the acid catalysts. Subsequentto cyclization, reduction with NaB&/NaOH eliminates mercury substituent.
Example: CHs CHs
o
1 ) 1 , C H 3 N O 2- ,2 0 ' 2) NaBH4,NaOH
?H'9r' ?
/f"-\ cH3l+cH3
cHz
2
\
q ?'.?" o^o'Y)
cu/-........ .Z-.c 3,>97:3
24o/"
I A. S. Gopalan, R. Prieto, B. Mueller, and D. Peters, TetrahedronLetters, 33' 1'679(1992)'
I -Mesityl-2,2,2-trifluoroethanol,l. Preparation:l
'8.J. Corey,X.-M. Cheng,K.A. CimPrxt' I : E.J.Corey,X.-M. Cheng,andK.A- (-tnq
Metal halides. Cleavage of terminal ePoxidcs: hd (l) can result in two halohydrins.Br p halohydrinscan be obtainedwith abou
H
9oHs
(r-|{coHu r o \-,N-e' Bu
(2)
o
A
n-C6H17
cH. - o I
ll
4t\/t"r, I ll cH3"'^\.,,^..-cH3
ce,z' coHscHs.-78", 100%
TiCl4,C7Hr6,-25"
>951
TiBrz(NRz)z , C7H16,0'
>951
CFs
ee 1, 100o/o
ester Asymmetric Diels-Alder reactions of a, B-unsaturated acids.2 The acrylate in cyclopentadiene (2) of this alcohol (l) undergoeslrwis acid-catalyzedreactionswith >97:3 diastereoselcctivitY.
HCt,H2O,25'
>954
-\ J . J . E i s c h ,Z . - R . L i u , X . M a , a n d G
2
Metal halides
o
! laniline,
(cH3)2Atcl -7A'
A rl
:ul.,rlr useful for cYclization of n :.-rction as terminatinggroups. ci:a,\n. as observedwith lrwis itl- \.rUHr/NaOH eliminatesthe
CHz
?" ?'.
\
H20-DME,
DI
o-)l( F
coo
CHr#
CHs
4
3,>97:3
t'
! . r t t : . 3 3 . 1 6 7 9( 1 9 9 2 ) .
rE.J. Corey,X.-M. Cheng,K.A. Cimprich,andS. Sarshar, Letters,32,6835(1991). Tetrahedron rE.J. Corey,X.-M. Cheng,andK.A. Cimprich, ibid.,32,6839(1991).
Metal halides. Cleavage of terminal epoxides; halohydrins.t The cleavage of a terminal epoxide (1) can result in two halohydrins.By proper choice of a metal halide either one of the halohydrinscan be obtainedwith about 95% regioselectivity.
r2)
o
.+
RCH(OH)CHzX +
RCH(X)CHzOH
n-C6H 1 7
CH" OH
r " l
ffcF3 t t l ll.-,,,,,,.*cH.
1 , 1 0 0 %e e
T i C l r , C z H r o ,- 2 5 '
>95o/"
5:95
T i B r 2 ( N R 2 ) 2 , C 7 H 1 6 , 0 ' >957"
94:6
HCt,H2O,25"
89:11
wotrd acids.z The acrYlateester in with cyclopentadiene r,.:-| 1,\DS J.J. Eisch, Z.-R. Liu, X. Ma, and G.-X. Zheng,J. Org.,57,5140 (1'992).
180
(rS,2R)-2n r}|.rra
(S)-or(R)-2-Methoxy'2/-diphenylphosphino'l,l/'binaphthyl
Methanesulfonyl chloride/Sodium hydrogen carbonate. p-Lactams.t Treatment of the B-amino acid I with 1 equiv. of CH:SOzCI at 45. in CH3NO2 containing suspendedNaHCO: furnishesthe B-lactam 2 in the highest yield reported to date for this cyclodehydration. The cis-isomer of I also undergoesthis
OH cH^)'..
+ HSiCl3
Pd-rRr'
99i
MsCl,NaHCO3 CH3N02,45'
/cH2coocH3
97%
HotcArun, 2
b+HSicr3;b reaction to give cis-2 (75Voyield). Yields are lower when applied to simple B-amino acids,probaLrlybecauseof lower solubility in CHTNOzand higher temperatures,75-80''
exo.1
I Y. Uozumi,S.-Y.Lee,andT. Hayashi,Terrohc
I M. F. Loewe,R.J. Cvetovich,and G. G. Hazen,Tetrahedron Letters,32,2299 (1991)' ( I S,2R)-2-(p-Methoxyphenylsulfonyl)emin Enantioselective addition of (CzH:t:Z
(S)- or (R)-2-Methoxy'2/-diphenylphosphino-1,1/-binaphthyl(l)'
N-sulfonylaminoalcohols, I was found to tr additionof diethylzincto aldehydescatalvzcdI chloride. Addition of calcium hydride or r cnantioselectivitybut can increasethe vield
c p-CH30C6H.Sq
ocH3
(R)-(+)-1
P(CoHs)z
I
c6HscHo + (C2H)2Zn
Asymmetric hydrosilylation of norbornene (2).t This reaction can be effected by in high regio- and enantioselectivityby reaction of 2 with clrSiH catalyzed to be converted product can The (R)-1. with complexed dimer (allyl)chloropalladium 96Va ee. (4) in (1S,2S,4R)-norbornanol
c-C6H11CHO +
(C2H5\2Zn
c*{:
I -phenylpropanol
(f S,2R)-2-(p-Methoxyphenylsulfonyl)amino-
lrl ate. ..:::
I cquiv. of CH:SOzCI at
\r-::
trr'. :hc P-lactam 2 in the highest L l - : . , ' m c r o f I a l s o u n d e r g o e st h i s
+ HSicl3 t
\ 7l_^.'-SiCf. z-'.\,/
ojll)r_ nn"
3 (exo,10O/"1 eo"/.I IH:KHco3 n'u' I \
zl1-oH z_\\,/ (1S,2S,4R)-4(93%ee)
5
b+HSicr3;rb,-ticr'; ..:.n appliedto simPle B-amino 75-80'. ' j:r.: hiqhcrtemPeratures, T
"'
(1R,2S,4R),95oloee
exo,1O0"/"
I Y. Uozumi,S.-Y.Lee,andT. Hayashi,Tetrahedron (1992). Letters,33,'71,85
::t r\. 32,2299(1991). ( f S,2R)-2-(p-Methoxyphenylsulfonyl)amino-1-phenylpropanol (l).
i n a p h t h Y l( l ) .
Enantioselective addition of (CzH)zZn to RCHO.| Of a variety of chiral N-sulfonylaminoalcohols,I was found to be the most effective ligand for asymmetric additionof diethylzincto aldehydescatalyzedby titanium(IV) isopropoxidein methylene chloride. Addition of calcium hydride or 4 A molecular sieves does not affect the enantioselectivitybut can increasethe yield.
CHs
-CoHs
/-R=\
p-CH3OC6HaSO2 NH
OH
(1)
r -1+)-1 1 , Ti(O-'-P04
C6H5CHO
+
(C2H5)27n
C a H 2 ,C H 2 C | 2, 0 '
tutu)a"r. H O H (S) , 97%ee c-C6H11fCHe
). I hi: reaction can be effected I *ith ChSiH catalYzedbY t - nroduct can be convertedto
c-C6H11CHO +
(C2H5\2Zn 77o/o
H O H (S),90%ee
182
(Danishefsky's diene)
,rdns-l-Methoxy-3-trimethylsilyloxy'I,3-butadiene
1 K. Ito. Y. Kimura,
and H. Okamura,
and T. Katsuki,
Synlett, 573 (1992)'
,aCuHu tl * CH3OOC-.._..N
Cl-h
,
t..
i-P{'H
c
1
f _ \ o
(1)
(S)-2-(Methoxymethyl)pyrrolidine.\""\""-CHt
?)
H 2-Methylenecyclohexenones.l A diastereoselective synthesis of a 2-methylenethe chiral cyclohexenone(5) involves use of (S)-2-(methoxymethyl)pyrrolidine(1) as group. exo-methylene the of generation auxiliary and as the leaving group for
I
///
Eiu",4
c6Hs{}LocH3
i-Pr''
l-Pr""f-6g6611.
(Y
coocH3
1)NBS, ccr4 2)1
>^
CHe
/'1..COOCtlt
:
. - I , ) a d d i t i o no f b e n z y l o x y k e t e n e s
[\.
.'riutcd B-lactams (3), which can .:rc acids(5).
t-
oc(cH3)3 N'Bzl 3 (15:1)
Hcl ,or" I (cH3)rcHoH I HO,,,.r.C6H5 | -r'i::
I
syn, syn 2
OBzl 4
Tetrahedron, 4t, 'nd S. Terashima,
syn, anti 3
R = CoHs-
98:2
R = H2C=CH-
80:20
R = BzlOCHz-
t2:BB
R = (l-Pr)3SiOCH2-
15:BB
2-aryl- and 2-vinylpropionardehydesreact with .syr, syn-selectivity, whereas the Bbenzyloxyaldehydesand B-triisopropyrsityroxyaldehydesreactwith syn, anti-serectivity. I M. Ahmar, R. Block,
G. Mandville,and I. Romain,Tetrahedron Lerters,33,2501 ogg2\.
l0-Methyl-9,lO-dihydroacridene/Sodium
affill
l.
Yru-\Z
,rrruy')icoocH(cH3)2 :
cu" cH3 cH3
ll
borohydride,
| / NaBHo
(1)
CHe Photocatalysis of radical cycrization. This system, when irradiated, can effect dehalogenationof aliphatic bromidesand aryl halidesvia a radical intermediate.rIt can also effect radical cyclization of 1-allyloxy-2-halobenzenes (equationl) in 76vo isolated vield.2
(2R3&5R)-4-Methyl-5'phenyl-3-phenylthio'2-morpholinol
rC. Agami, F. Couty, L. Hamon, B. Prince. and (' I 2 C. Agami, F. Couty, B. Prince, and C. Puchcx.r?v
CHr
zYt
l^i;
ll l. -$OCH2CH=CH2
76"/"
t
i
l
t
(Y) \_,,^-o
-
Methyl(phenylseleno)malononitrile,
t M. Ishikawa and S. Fukuzumi, Am. Soc'' 112' 8864 (1990)' 2 G. Boisvert and R. Giasson, Tetrahedron Letters' 33,6587 (1992)'
ro-r.ot'l
# lor,"(i' I cur,u"l'-*" cH. I L cHs Asymmetric synthesisof N-methyl'a-amino
I
cH.4 This reagent is prepared by reaction of
(l)' (2&3&5R)-4-Methyl-S-phenyl-3-phenylthio-2-morpholinot' glyoxalwith (R)-NThis chiralmorpholineis obtainedin 85Voyield by reactionof in water'r andthiophenol methylphenylglycinol
..oH gHo I
NC
C6H5SeBr. Radical additions to alkenes,t Unlike rcd containing OR, SR, or NR2 groups (l6.ltt-1 of AIBN undergoes1,2-additionto alkenes p alkenesproceedsin high rick 1,2-disubstituted
CsHsSH
Bu
cH2
1 ,A I B N cHct3,60'_ 97%
esters'2 This morpholine can be used
asachiraltemplateforsynthesisofN-methyl-a-aminoesters.Thusreactionwithan group by an alkyl group by the alkylcopper involves displacementof the phenylthio reactionwith an alkylzinc contrast, In 90:10). (about usual Sn2 processwith inversion possibly via an iminium retention, complete iodide involves substitutionwith essentially
C6Hu"\.CHs
intermediate.Thealkylatedproduct(2)isthenoxidizedtoanoxazinone(3),whichon provides N-methyl-a-amino treatmentwith vinyl chloroformatefollowed by hydrolysis esters(4)inhighopticalpurity.Thisapproachtochiralaminoacidsisunusualinthat dependingon the choice of the either enantiomercan be formed from the sametemplate (expensive)is not recovered auxiliary chiral the organometallicreagent.Unfortunately,
c2H56'\.''cHa
--
r2..*
for reuse.
'
Prznt ,OY"
aoYot C6Hr,."
\rAr, r
CHs 2 (>96%de) 1) cH2=cHococl 2) HaO+. CHaOH -8O"/o
-
!"ror?'60-80'/'
(oYo cuH;"\ry e' CHs 3
r D . P . C u r r a n a n d G . T h o m a ,A m . S o c . , l l { . 1 J . \
CH3O--.7,O
r I
HtrtAPr CHs 4
Methyl trifluoromethanesulfonate, CH.OTf . A new route to o f5+2]Cycloaddition. activation of an unsaturatedpyrone such a:s a pyrylium salt (a), which undergoes[5-1)cr to give 2 in 84% yield.
Methyl trifl uorcmethanesulfonate 1 C. Agami, F. Couty, L. Hamon, B. Prince, and C. Puchot, Tetrahedron,46,7003 (1990)' 2C. Agami, F. Couty, B. Prince, and C. Puchot, ibid.,47,4343 (1991).
NCVCN
Methyl(phenylseleno)malononitrile,
cHr
(1)
secuHu
This reagent is prepared by reaction of the anion of methylmalononitrile with rpholinol (l). tr :-.rctionof glyoxal with (R)-N-
C6H5SeBr. Radical afulitions to alkenes.r Unlike iodomalonitriles which do not add to alkenes containing OR, SR, or NR2 groups (16,183-184), this malononitrile in the presence of AIBN undergoesl,2-addition to alkenes possessingthese groups. The addition to 1,2-disubstitutedalkenesproceedsin high yield and with high regioselectivity.
,.O,J|OH -
-
t|
i!
l
|
E e l - .i *c6Hr'."l=lnscuHu
I,A|BN
CHs 1
Bu
cH2
"+#*
NC
cH./fsec6H5
'this
Bu
morPholinecan be used t r\ |'r.- c:tcrs. Thus reaction with an r, --'up bY an alkYl grouP bY the . -':.r\t. reactionwith an alkylzinc tc -. .ntron,possiblyvia an iminium il..-.: i,, an oxazinone(3), which on i: . ..rr providesN-methyl-a-amino ;i^ ': .rnrinoacidsis unusualin that rpi,'. Jcpcndingon the choiceof the [\:. ::\ (cxpensive)is not recovered
CN
Nc\
cH.
/cN
SeC6H5
(\cH,
CoHs syn/anti=80:20 NC 6p SeC6H5
\ / t
^ ,, ^.'\-CHg U2H5U
92"/o
CH3"/\"\cH3 oc2H5 syn/anti -- 25 :75
: t. ,'i+ ^ :': -: -
.'O'-ZO | I | I ^ . . * t \ N A'iP r CoHs CHs 3
I D. P. Curran and G. Thoma, Am. Soc., ll4,
4436 (1992)-
Methyl trifluoromethanesulfonate, CH3OTf. A new route to complex seven-membered rings involves [5+2]Cycloaddition. activation of an unsaturatedpyrone such as 1 with CH-:OTf (2 equiv., 20") to form a pyrylium salt (a), which undergoes[5*2]cycloaddition at 25" when exposedto CsF to give 2 in 847o yield.
Methyltrioxorhenium
hydrolysisof epoxidesto trans-1,2-diolsThrs additionof amines. 2 cH3oTl, cH2cl2,20'
1Hp --.: 'Fr
^,, .-\--CHt UH3 CHa
I
a\ t
I c'r sa7"I orrr/cFl2ct2 I ru'
I xrc 6'
l
7CA
1 H?C 6'
cHZ"".'oH
I
$a
Aldehyde olefination.a CH-rReO. (lt rs aldehydeswith a diazoalkaneand a phosphtr The actual catalyst may be CHTReO:OPR' I aromatic aldehydesand also to enals' Somc rn only moderate Yield.
2 (3.8:1) of phoboids such as tigliane (3)' Phoboids Note that 2 correspondsto the B/c ring promoters' are of interestas highly potenttumor J' Org'' 56' 626'1('1991) 1P.A. WenderandJ.L. Mascarefras,
CH3-..,/.CHO
in cH2cl2 or coHscl at 25"' neous catalystfor metathesisof alkenes
CH3CH=CHC2H5
CaHeCH=CH2
1 Al2O3/SiO2 -***
Nlta
CHg\...\--COOCzHs l CHs (E/Z= 85 : 15)
(1)' Methyltrioxorhenium, CHrReOr with HSn (CH.r)3and purified by vacuum This oxide is preparedby reactionof Re2O7 sublimation'ltissolubleinorganicsolventsandalsoinwaterandisstabletoairand .-._otefinmetathesis.2CHrReormixedwithAl2o3/Sio2isaneffectiveheterogeacid.r
+
I
CHg
ficHo
*
Nza
ozN*
fi*cooc4 ozNV
cH3cH=cHcH3 CaHeCH=CHCaHe +
C2H5CH=CHC2H5
CHr=611t
catalyst for epoxidation of alkenes with Epoxi.dation.3 CHrReOr is an effective or water at -10'to 80"' It also can c^tzlyze H2O2 in l-butyl alcohol, tetrahydrofuran'
"31 (Elz=s7 * .\. Herrmann,J. G. Kuchler, G. Weichsclhlu ntm., 372,351 (1989). \\'.A. Herrmann, W. Wagner, U.N. Flessmr' I' r.J., 30, 1636 (1991). \\. A. Herrmann, R. W. Fischer,and D' \A \|er ' \ \ . A . H e r r m a n na n d M . ' V ' l a n g ,i b i d ' . 3 0 ' l r ' r l
Methyltrioxorhenium
193
hydrolysisof epoxidesto trans-1,2-diols.This secondaryreaction can be suppressedby addition of amines.
CH."\'-CHs
o -
OH
1, H2O2 -10" 100"/"
No
cHs/YcHs OH cH3/oH
CHe
I '
a\ t
1, H2O2 25"
l
/-Yo \-l
70v" 1, H2O2 25" . 90"k
cHNoH
ot>-rot
Aldehyde olefi.nation.a cHrReor (1) is an efficient catalyst for condensationof aldehydeswith a diazoalkaneand a phosphineto form an alkeneand a phosphineoxide. The actual catalyst may be cHrReozoPR3. The reaction is applicableto aliphatic and aromatic aldehydesand also to enals. Some cycloketonesundergo this olefination but
li.o
in onlv moderate vield. 2 (3.8:1)
CH3-- -,CHO Y
l. ..r.h as tigliane (3). Phoboids
I
rurz\coocrHu
ir ( ll.), and PurifiedbY vacuum '- .\.rlcrand is stableto air and
82lo
CHs CHs\..\_-COOCzHs I CHe ( E / Z= 8 5 : 1 5 )
I
1, P(C6H5)3 C o H o2, 0 ' ,
+
O=P(CoHs)s +
Nz
1,PBu3
[aY"'o
l\tr^coocrH,
z*cooc2Hs I ll orNV
+
'*#-
orN& \r( )- is an effcctive heteroge< lt.('l at 25'.
C2H5CH=CHC2H5
ih,
+
CH2=CH'
l : : ipoxidation of alkeneswith ' ttr t10".It also can catalYze
o=PBuo
N2
(ElZ--97:3) :W.A. Herrmann,J.G. Kuchler, G. Weichselbaumer,E. Herdtweck, and P. Kiprof, J' Organomet. C h e m . ,3 7 2 , 3 5 1 ( 1 9 8 9 ) . rW.A. Herrmann, W. Wagner,U.N. Flessner,U. Volkhardt, and H. Komber, Angew. Chem' Int' Ed., 30,1636 (1991). 'W.A. H e r r m a n n ,R . W . F i s c h e r ,a n d D . W . M a r z , i b i d . , 3 0 , 1 6 3 8 ( 1 9 9 1 ) . 'w.A. Herrmann and M. Wang, ibid., 30, 1641 (1991).
194
carbene complexes
Molybdenum
Molecular Sieves. Stereoselectivity effects.l There are several recent reports that molecular sieves can improve the stereoselectivity of various reactions such as the Sharplessepoxidation (e.g., f3,51). The beneficialeffect has been attributedto water-scavengingby the sieves. of the Pd-catalyzed Molecular sievesalso show a markedeffect on the diastereoselectivity I). ln thesereactions, (equation chiral acids with cyclizationof cis-1,2-divinylcyclohexane the diastereoto increase in some cases additions of molecular sieves wele found
,ocH3 (Co)sMol Bu
CH2=66611
molecular cyclization of the carbene complcr
bene I with methyl acrylate in THF ar 6-i' pn 2 in 71.Vo yield.2
H /fl \'/
f/'\+,'\CH, | | :"2 |
1) BuLi 2) Mo(CO)6 3) cHqoSO^cFl -
eo1on.1,,o{:!o
|
,,\LJ
+
v/|"gzvrt2 H
Mno"'(CHq)^c=O
R*COOH
*
|(CHj3C=CR
.v
R = (CH2)2CH3
'*o"ot
ocoR'
CHz
>
T .t(Rl I
Y.T..--/
6 H
selectivity, in one case from 0 to 54Va ee. In more cases,the addition of molecular The highest selectivity obtains with sieves could even reversethe diastereoselectivity. Lancaster4 A and 13X sieves,both of which have sodium as the counterion.The steric effects do not result from elimination of water, since sieves containing ZOVoof water show improved stereoselectivity.No explanationis available at present,but a surface effect is one possibility.
[
r
I .r - rHF,6s" | ,#uo(co)o - l ( i l l\--,/'.. ocHo L
l
I q iI I
The processhas been extendedto the drr molybdenum carbene4 at 60" results in a r [3.3]sigmatropic rearrangementto hexahrdr analogouschromium complex with 3 also rc lower yield. An electron-withdrawinggroup r
I L. Tottie,P. Baeckstriim, Org.'S7'65'79(1992). andA. Heumann,J. C. Moberg,J. Tegenfeldt, H_
\- -*co@ Molybdenum carbene complexes. Thesecomplexescan be preparedin about55Voyield by reactionof RLi with Mo(CO)e followed by methylation (equationI). .l) RLi,ether,0"
Mo(CO)o
+
2) cH3oso2F,o' 55%
3
cooc2H5
/ocH3 (co)sMol
t
R
Cyclopropanation.r These carbenesare particularly useful for cyclopropanation of electron-poor olefins. The reaction occurs under milder conditions and at a taster rate with molybdenum carbenesthan with chromium- or tungsten-derivedcomplexes'This cyclopropanation has been used to trap a molybdenum vinylcarbene generatedby intra-
5
D. F. Harvey and M. F. Brown, Tetrahedroa l.ctt, Idem, Am. Soc., 112,7806 (1990). D.F. Harveyand K.P. Lund, ibid.,113.5{x6 rt,
Molybdenum carbene complexes
:p,n. that molecular sieves 3. :hc SharplessePoxidation tc: .eavengingby the sieves. el;irivity of the Pd-catalYzed qi.r:r\)nI). In thesereactions, i :. increasethe diastereo-
raj o
75o/o
cH{r tar"u cH3"V"-o5,ar."u"u cH.-.-2...--d
€(F
8r
"r1-""\t, o
1o>-cuHu
CHS
7-o1-coHu
(
)
d)--t"'
" "*- >
C:\'H. double addition to nitriles to form lert-amta addition is about four times slower than th
additiontowittig{ypereactions.,hislaboratoryhasreportedsevera|novelusesforthese compoundssuchasaselectiveacetalizationofaldehydes(equationl).Acetalizationcan alcohol in almost quantitativeyield' also be effectedby the system SbClr/Al and an (l)
RCHO
+
Sb(OC2H5)3 + CH2=QHCH2BT
RCH(OCzHs)z+
o jl
(ll) gt'l
\q2
+ Al + C2H5OH
sbcrr,25.
?
c6H5cN
C6H5COCH3
THF {6
&JC€O +
crHuoFR;;AcH, c2Hso\
PC'rlu RrARz
r"-}cocH3
4 &rc€
C6H5CH=CHCN +
The reaction of anhydrous BaI2 with
lithiumbiphenylide(2equiv.)inTHFprovidesareactivebariumspeciesthatreactswith -7g. to iorm allylbarium chlorides.These reagentsreact with high allylic chl,oridesat a-selectivitywithcarbonyl"o'npound'toformhomoallylicalcoholswithretentionof configuration.
3 BuCeCl2
1a"t-
I Y.-2. Huang, Acc-Chem.Res',25, 182 (1992)'
Organobarium reagents. Altylbarium reagents;homoallytic alcohols't
C6H5CN +
3 CH3CeClz
Bu ,FNH
t-Bu
+
3 CH3CeCl2
6ar
Organocerium
OH
'l ) Ba* 2) C5H11CHO
'(Y"'
rd\rersl.r Both RzAlCl and ,:'::: rclectivity.
I 4vc^H,. t -
.......................................-".,'........* 560/o
" CHs (Z/E=99:1, o,lY= 77 1231
CHs p1 o ^'tt(CHg)z + cH:
r€agents
s4n-1
QoHs
99:1
OH
i 1
)Ho -
^-OCZHS
+
sVn-2 (ZlE= 98:2, crly=92:8)
99: 1
CH,. t1'..2
rA. Yanagisawa, Am. Soc.,f13, 8955(1991). S. Habaue,andH. Yamamoto, l-:
r()ql).
h .: ! , ttt'rs, 33,4353
(1992)'
compounds.In {,:r.rn()antimony r:..: .cvcral novel usesfor these s , ,.iLtittionI). Acetalizationcan r: .,lmostquantitativeYield.
Organocerium reagents. Addition to RC=N and >C:NH.| Organocerium reagents (RCeCl2) undergo doubleaddition to nitriles to form /ert-aminesoften in high yield. The rate of this double addition is about four times slower than that of addition to a carbonyl group.
C6H5CN
+
Bu I
rHF'-65- 25'
3 BuCeCl2
C6H5-f-NH2
eoo/o---_
Bu quant.
o
C6H5CN
+
C6H5COCH3
BUCECI, -----' >
BU ?' ... . + CoHs-fNH2
CoHs-fOH CHa
CHs
78:22
crHroFR;;AcH, ,
C2H5O',roCrHu
r.+cocH3
+
4 Bucectz--iu*
RrARz
C6H5CH=CHCN
+
3 CH3CeCl2
?' ,r:t
HrN-t-\ Bu
cH? ?t'
-46%-
/--J-NHz
C6H5CH2 i '- Ltion of anhYdrousBaI2 with rc ^.:nurTlspeciesthat reactswith i I rc.c reagentsreact with high ol..,re alcoholswith retentionof
Bu
Er.rH t-Bu
Bu -+ 3 CH3CeCl2 62%- t-tr-f*t, CHs
?u
/-l-o{ Bu
CHg
206
Organocerium reagent
Thelastexampleshowsthattheseorganoceriumreagentsalsoreactwithketimines tertiarY amines' form to a-Silytketones.'Organoceriumreagents(15'221)addtothecarbonylgroupof enolates(a)' which undergo alkylation on trialkylsilylketenesto to,,n- B-'ityt cerium ketones.This tandemalkylation can be used reactionwith RI and HMpA to form a-silyl ketonesby the choiceof RCeClz and RX' to prepareeitherone of the two possiblea-silyl
R3sicH:c:o
OC"1ffll NHacr
Prcecrz- f rHF'-78'> ln.si./e,
? R3si---Apr
)A
Rs= t-BuMez
^-^,I cn.r
or-r.
I HMPA
V
o
tl RsSi-...,_Ap.. I CHs
(3).3 The synthesis Asymmetric synthesisof tll-l,3.diphenyl-1,3-propanediamine of CeHsCeClz addition by amines chiral of of 3 is an extension ot a synthesis of CcHsCeClz to the addition Thus (C6H5Li/CeClr) to hydrazont" 1tl'Zl'l-218)' be cinnamaldehyde'provides 2' which can dihydropyrazoleI' preparedas shown from
t) H2NNH2(-60%) 2) (l - BuOCO)2O(-90"/')
t-Boc.'N-N
/ \ r\\ ceHs-'^\,,/ /
C6H5'"\'-CHO
(dl-trans)'2
1)rFA
2) Hr. RaneyNi -'-;;-so'/"-
CeCt
rE. Ciganek,J. Org., 57,4521'(19921: Y. Kita, S. Matsuda,S. Kitagaki,Y. Tsuzu\r.|| -1S.E. Denmarkand J.-H.Kim, Synthesi-s. llr tl a N. Greevesand L. Lyford, Tetrahedron Lenat
Organochromium reagents. RCrClzt Reagentsof the type RCrCI; r -J by reaction of CrCh(THF)r in THF at reagentsalkylate aldehydesin yields of { aromatic aldehydes.They generalll do rxr I hydroxyl, methoxyl, or dimethylamino Iru4 CHrCrClz(THF)r in good yield with rcn lacking such grouPs'
o C8f,rC
X cH3cH3
c6H5Li/cecl3 rHF, -78' oc - 94"/"
1
cunu--(.zlcuH,
rHF, (((( +
Jt -oH CHs-
converted into 3'
H Boc.. N-N
CeCl3.7H2O
NHu - NHz | i
c6H5Sc6H5
o o H i
l
l
cH3"AY\cH3
lsr
CHs C. Beirich,A. Hamsen.T \l'{ T. Kauffmann, t57 /L992).
dl-3
Ultrasound-assistedpreparation'aCeCl:isnotsolubleinTHF'buttheheptahydratewhensonicatedlnrnpisconvertedintothesolubleCeCI:.THF.Reactionof in srtu' CeCl: 'THF with RLi provides RCeCl2
Organocopper reagents. Stannylcupration of proparglanitct ,mines (1) react with BurSn(Bu)CutC':-i :-substituted 3-(tributylstannyl)allllamtrrs ..]-disubstitutedallylamines (3).
Organocopper r€agents
!s::. irlsoreactwith ketimtnes
THF, ((((
C e C l 3 .7 H 2 O +
Rut I
CeCl3'THF -:
.,,:.1lo the carbonYlgroup of , .,rrch undergoalkYlationon i r:-.1ifl] alkYlationcan be used r ':, choiceof RCeClzand RX'
'.-.ct 4 ^ ^ , ':'"
I BuCeCl2 |
77v"l n | \ - ro i Bu. ,OH \./ \-.-
? HSDI\/,,/\pf
.l
r
l l
rE. Ciganek,J. Org., 57, 4521(1992). 2 Y. Kita, S. Matsuda,S. Kitagaki,Y. Tsuzuki,and S. Akai, Synlett,401 (1991,). I S.E. Denmarkand J.-H. Kim, Synthesis, 229 (1992). 4 N. Greevesand L. Lyford, Tetrahedron Letters,33, 4759(1992).
ncdiamine (3)'3 The sYnthesis r. hr addition of CaHsCeClz a.l.:::r(tnof CoHsCeClzto the :f ..:-. providcs2, which can be
t - 3c c N-N \\ la.-"J
C6H5Li/CeCl3 THF, -78" > 85 -94"/"
1
Organochromium reagents. RCrCl2t Reagentsof the type RCrClz can be preparedin situ or in crystallineform by reaction of CrCh(THF)r in THF at -2O' with RLi, RMgX, or (C2Hs)rAl. These reagentsalkylate aldehydesin yields of 4O-90Vo, being highest with CH-lCrClz and aromaticaldehydes.They generallydo not alkylate simple ketones,but ketonesbearing hydroxyl, methoxyl, or dimethylaminogroups on the a- or B-position arc alkylated by CH:CrClz(THF)3 in good yield with very high selectivity in the presenceof ketones lacking such groups.
o l- -oH cHs' X cH3 cH3
o o H i l l cH."'^\*cH. l CHg
\N: NHt
A"uru
CH3CrCl2,20o
cH3/oH )( -oH CHs- X cH3cH3 cH3pH 9H
cH.#cH" l CHs
: T. Kauffmann, Ber., 125, C. Beirich,A. Hamsen,T. Mijller,C. Philipp,and D. Wingbermiihle, t57 /L9921.
d t- 3
s" .'lc in THF, but the hePtahYr , . . ' l r C c C l r ' T H F . R e a c t i o no f
Organocopper reagents. Stannylcupration of propargylamines,t Boc- or Si(CHr)r-protected propargylrmines (l) react with BurSn(Bu)Cu(CN)Li3 and then with an electrophile to form :-substituted 3-(tributylstannyl)allylamines(2). These products can be converted into 1.2-disubstitutedallylamines (3).
OrganocoPP€r rcag€nts
1) Bu3Sn(Bu)Cu(CN)Li2 2) cH3l
H-------\
gu"sn-YNHBoc " l CHe
NHBoc
Allylic organocopper reagcnts.' by reduction of CuCN' LiX. reacts r organocopperreagents,which couplc
2
1
"nt)^"o"' CHs BzlPdCllP(CoHs)slz,
c'l
CHs,,-/-,,-...Onc
710/o
CH::Z
3 Cyclica-alkoxyorganocuprates.3Acyclicopticallyactivea-alkoxyorganocopper reactions'In contrast' reagentsunfortunatelyundergo racemizationduring 1,4-addition acyclica-alkoxyorganocopperreagentcanbestableat-Ts".Enantiomericallypure acid (15,171) via reagentsof this type have been preparedfrom (R)-3-hydroxybutyric
1) Cu' 2) C6H5CO
CHe
t -
cttr,,,,.^ycl
thealdehydeltogive4-(tributylstannyl)-1'3-dioxanes(3),whichareseparableby
CHs-
OMOM | -\ v -cHo
1) LiSnBu3 -2\ t\4O1M9!*
OMOM MOMO I I CHsSSnBu3
BF3Et2o
The particularvalue of this routc t range of functional groups: enonc. cp
2
1
o^o r l
o^o l
l
+
*
(R,R)-3
(R,S)-3
l
flashchromatography.Thecorresponding4-|ithio.l,3.dioxanes,formedbytransmetalaThe axial isomer' derived tion with BuLi, differ markedly in conformationalstability. fromthe(R,R)-3isunstableabove-TS.andrearrangestotheequatoria|isomer'The with BuLi' then CuI' and a-alkoxycopper reagent4, formed from (R,S)-3, by treatment finallyTMEDAat-78.'reactswithethylpropiolateinthcpresenccofClSi(CH3}to form a single adduct (5) in 92o/oyield'
o^o | | cHsscu-TMEDA-Lil
+
'9 H---< bc2Hs
4
cHa
"'snBu3
cH"*
cH3/-*snBu3
clsi(cH3)3' rHF'-7g'cs2"/"
Y
cHl"v
o
l
z
cl
Amide cuprates;B-lacnms.' .l ':act with 1,3-dienoates to give rrrth rquationI). This reactioncanbc crta
,, CuHu*co2CH3
o^o
"r"&oc2H5 o
r I with the dienoate2 follo*cd tn :calmentof 3 with (C6H5)1P?rSt;
209
Organocopperreagents
N SN-VNHBOC I CHs 2
}c:
Allylic organocopper reagents.a The activated copper species (Cu+), produced by reduction of CuCN .LiX, reacts with allyl chlorides and acetatesto afford allylic organocopperreagents,which couple with various electrophilesin good yields'
CHs\/'..-..oAc
^-*,,*
CHs-.,/'-,,,.Cu*
--cH,
n-"-:6HsCHO
-
syn/anti=70:30 lr .:.tirc a-alkoxYorganocopPer f-.,.:Jrtionrcactions.In contrast, -So. EnantiomericallYPure a: r ; : , ' r r b u t y r i c a c i d ( 1 5 , 1 7 1 )v i a -l r. which are separablebY
:
or,,toM :
'
BF3'EI2O
snBu3
CH:r
t cHr,,,,,ycr
1) Cu* 2) CsHsCO
=cH,
74"/"
The particularvalue of this route to organocopperreagentsis that it toleratesa wide range of functional groups: enone, epoxide, carbamate,nitrile.
r\
- "'snBue
-
1) Cu* 2) C6H5CHO
lFa.3 h r.,ttcs.formed bY transmetala'Ihe axial isomcr, derived h,:::r ',, the equatorialisomer.The 1c. :J:r'-nt with BuLi, then CuI, and rr :'rr prcsenceof ClSi(CHr)r to
c cC2H5
clsi(cH3)3, THF.-78oc > 92v"
CoHs
CHz
Amide cuprates; B-lactams.s Amide cupratessuch as [BzlSi(CHr)3N]rCuLi (l) react with 1,3-dienoatesto give with high or exclusive rcgioselectivitythe l,4-adduct coupling.Thus reaction lcquation I). This reactioncan be extendedto a three-component
NHBzI
(l) CuHr*CozCHs
+
1
#
cuHu*Co2CH3
'f I with the dienoate2 followed by trapping with CoHsCHO gives 3 in 77Vo yield gives the B-lactam4. Treatmentof 3 with (C6H5)2P/PyS)2
Organocopper r€agents
+ H--+ Bu3Sn(Bu)Cu(CN)Li2
CHs\/\4CO2i-pr+C6H5CHO+1
pu(Bu)(CN)Li2
Bu3Sn, BzINH OH
/)
CHs
cH.
\
H
$cuH.
99:1
BuCuMgBrl'BF3 THF,s(cH3)2 >99:1
1)CuCN
Bu(CN)CuMgBrBF3 THF,2 Li
zl r-i$ocx ..\r-Li ll
also undergosubstitutionreactionscan Vinylcuprates.Lr Vinylcuprates(2) that can vinyl cuprates can convert a l-alkyne be prepared as shown in equation(lI)' These
Y
3)Or
|
I ocH3
ocH3
I
R
l \ (l) lll ce' zr(H)cr'
iH
/
Bzl
/--
+
1)2 cH3Li 2) (2-ThlCu(CN)Li
",'''"0'
N)Li2
'cu(c
ws
,,^\r\2
99: l
oR' R3sio--\,,\coocH3
t R35iO-..-.,.(,.....,,\COOCH3 :
R'= BOM R=CHg
1 41 1 9.9:1
87"/o 88/"
Bzl..-*-Boc
(CH3)2CuLi, ClSi(CH3)3 THF,-78'- 20'
cHs,,.-..........Z-.coocH3
81"/"
Bzl..t*-Boc
cHsl-:,^coocH3
eH.
(s)-3
syn-4
C113,,,
(22R)'2(98:2) CH.
Conjugate addilion of BuCu.tT BuCu activated by ISi(CHr)r adds to the chiral crotonateI with excellentdiastereoselectivity. In contrast,additionsof lithium butylcuprates arc highly dependenton the exact compositionof the reagentand on the conditions,and
O
3H:,
(22S)-2(97:3)
(s)-2
1 ( 2 2 R 1 - 2( 1 0 0 : 0 ) loxt - and y-ureido'a , B-enoates't6 adds to 7-alkoxy n: '- j.-lcthvlsilane rI; -, -.tivitv obtainswith a benzylh95% ee
L:.:rx has reviewed reactionsof \r' rt. Ni(ll), Pd(0), Pd(II)' and u:r.:.lrrly effective for coupling of can promoteconjugate \i -.rt.rlvsts r:: r:lcludesa list of more than 35 [,,:':matskY reagents. :.',phtrric andmoisture-sensitive' but it is exPensive'A s I :Lrurccs, - \ 1 i \ * i t h Z n C l 2 i n e t h e rt o f o r m J ^ ' nrccipitationwith dioxane'The
Altylethylzinc.3 A reagent(2) of this type is preparedby hydroborationof l-hexyne with dicyclohexylborane(1 equiv.) to form an (E)-1-alkenylborane1, which undergoes transmetalationto form 2 on treatmentwith diethylzinc.This reagentaddsto an aldehyde in the presenceof the catalyst(-)-3-exo-(dimethylamino)isoborneol(DAIB, 3) to form a secondary(E)-allylic alcohol in 70-95% yield with 79-98% ee.
BUC=CH
B'-z-a("-n"r)
G,,,,
1
I etzn { CoHs
3, 00
C6H5CHO +
7O%)' aldehydesto form allenesin satisfactoryyield iC.E. TuckerandP. Knochel, Am. Soc.,lf3' 9ft88(1991)'
t :-, : F:l
-.lBt Zn
RcH2-< )cl Zr cPz
1
Osmium(IID chloride, OsCl3. Oxidation of B-lactams.r In the presence of OsClr (catalytic), B-lactams are Highest yields obtain oxidized by a peracid in acetic acid to give 4-acetoxy-B-lactams. $ith peracetic acid, but C6H5IO and C6Hsl(OAc)z can be used. This oxidation is
236
0smium tetmxide
n ,,-NH (
OsCl3 cHecogH,HoAc
a(oo" /FNH
78o/"
o'
R.SiO
R.SiO "
cH.+{oA"
l H cH3,,\-l
o/-*^
o/-*'
2 (>99%de)
1
intermediate in the of I into the acetate 2' a key particularly useful lbr conversion presumably an oxoosmium(V) complex is involved' synthesis of carbapenemantibiotics. Letters'32' S Akutagawa'Tetrahedron I S. Murahashi,T. Saito,T' Naota'H' Kumobayashi'and 214s (19er).
Note that the mirror-imagereciprocitl ber* basesthemselves. A further improvement can be effected t'r basedon olefin),which accelerateshl drolr srs
99/o de) ci.:ii 2. a keY intermediate in the rr "'.mium(V) complex is involved. \
\\utaqawa, Tetrahedron Letters, 32,
Note that the mirror-image reciprocity between I and 2 is greater than in the cinchona bases themselves. A further improvementcan be effectedby addition of methanesulfonamide (1 equiv. basedon olefin), which accelerateshydrolysisof osmateesterintermediates.This catalyst is useful if the alkeneis trisubstitutedor 1,2-disubstituted, but is not useful in the caseof terminal alkenes.Addition of the sulfonamidepermits osmylationsat 0", with enhances enantioselectivity. Use of these phthalazineligands and addition of a sulfonamideresults in enantioselectivitiesof 95-99.5Vo in the caseof nonterminalalkenes.In general,reactionswith ligand I are somewhatmore enantioselectivethan those with ligand 2. However, the use of these dihydroquinidine and dihydroquinine phthalazine ligands does not improve the enantioselectivity of cis-disubstitutedalkenes.2 The problem in this case can be solved by use of carbamate ligands such as (9-Oindolinylcarbamoyl)dihydroquinidine, DHQO-IND (f).
cHs H
15. 140-247; 16,249). In the ar:rJ hv useof estersof dihydroquiobtainsby use k: rnantioselectivity
poHs
OsO4,K3Fe(CN)6 1, K2CO3,I-BuOH/H2O
H
to\,
./ot
CH.t"'/1",'6u9u H H
l
r,,:rthalazinewith dihydroquinidine
237
72o/oee
Asymmetric monodihydrorylation of 1,3-dienes.t This osmylation can be effected with use of [1,4-bis(9-O-dihydroquinidinyl)phthalazine (1) as the ligand. In this reaction the productswith few exceptionare ene diols; generallyosmylationoccurswith the more electron-richdouble bond. Some regioselectivityis observedwith nonconjugateddienes, with a preferencefor trisubstituteddouble bonds over terminal ones.
\ . .N)
t ) \ ,
OH I
1 OsO4,K3Fe(CN)6,
ocH3
c6Hu'-\-A--coHs
"urrl-f'\-"u
84%
OH >99%ee OH
cHrM
-G""./f:cH, cHz
*.r.-.1if-oH
OH
3 :l 72o/" Ae
9oo/oee
?t' cH3-'\.."\--\
cH2;
ct'.'ot "t.-Ji*"t, 98o/oee
t
238
Osmiumtetrcxide
Asymmetric dihydrorylation of enol ethers.a This reaction can be effected in high yield by reaction with K2O3O2(OH)+,K:Fe(CN)6, or K2CO3 catalyzedby either (DHQD)2-PHAL or (DHQ)2-PHAL. The dihydroxylation can be carried out on the
Asymmetric synthesis of hydmn-1 p, y- and 7, D-unsaturated estersis accom y-lactones, generally in 96-98'? ee. scrystallization. mtx
R3SiO
Z\r\,-cH3 l t l cH.oA.'
60 - 851
cH3o 99% ee K2OsO2(OH)4, K2CO3 K3Fe(CN)6, (DHO)2- PHAL
R3SiO
-A
,"oA-.\-*
94o/o
(ZE=99:1)
"r.oV
CHs
(r Oa f,
cH3soy'{H2 HP I t-BuOH.
o
K2OsO2(OH)a, K2C03 KsFe(CN)6, (DHQD)2- PHAL
R
o 2
cHg
(E)
.ROU 997o ee
qude EIZ mixture obtained by conversionof ketonesinto enol methyl ethers or enol silyl ethers. Asymmetric dihydroxylation of enynes.5 Even though alkynes can be oxidized to a-diketones by osoa, 1,3-enynescan be convertedto ynediols exclusivelyby osmiumcatalyzedasymmetric dihydroxylation using a dihydroquinidinecatalyst. The enantioselectivity in this reaction can be markedly enhancedby use of a new ligand l, in which two dihydroquinidinesare connectedby a phthalazinespacergroup. Using this new ligand, 1,3-enynesin which the ene group is ,rans-disubstitutedare convertedinto 1,2-diolstn 73-97o/oee.
60 - 85a
A symmetric dihydroxy lation of allct vlation, can accelerateOsOa-dihvdrorr DABCOs have been shown to bc usefu DABCOs of this type availablefrom (S.S is l.
,#ra"H20
cH2oTBPS (s,s)-1
Nr K-'Feo C^H^'/; " " -'-t' -CsHs ,
Review of asymmetric dihydrox-vbn *as initiatedby Criegee'sobsenatronrn
Osmium tetmxide
ff :. rc.tction can be effected in ,- K:CO3 c talYzedbY either ! a:r :' can be carried out on the
Asymmetric synthesisof hydrory-y-Iactones.6 Asymmetric dihydroxylationof estersis accompanied by spontaneous lactonization to hydroxy B,y- andy, 6-unsaturated generally in 96-98% ee, which can be increased, to l00Va by a single TJactones, crystallization.
o CHs
,*oA-'x-t
mix a or p, cH3s02NH2 t-BuOHH , 2O,0"
'oF(* or
....."................'..'...,-..........................* 60 - 85o/o
Y" o
ar-.r^r)
(R,R) 100o/o ee
99% ee
o
-
('(Y"
(S,S) 10Oo/o ee
o
"
tl
\\
OH
60 - 85%
Aol (
o \--^\.\_,-R
-n3v
r
l
:- .rr:halkYnescan be oxidized to r r "r.liols cxclusivelyby osmiumd:'-Lrinidinecatalyst.The enantioc..: 'r\ use of a new ligand I' in r::.,i.1/inospacergroup' Using this u,:. Jr.ubstitutedare convertedinto
: HO
HO (R,R) 100o/o ee
99o/o €€
e. r:rl()cnol methyl ethersor enol
239
(S,S) 10oe/o ee
Asymmetric dihydroxylation of alkenes.T DABCO, known to acceleratedihydroxvlation, can accelerateOsOa-dihydroxylations;new C2-symmetrical2,3-disubstituted DABCOs have been shown to be useful for asymmetric dihydroxylations.Of several DABCOs of this type availablefrom (S,S)-threitol1,4-dibenzylether,the most effective is l.
/ l-N. rl'-)-cn2oTBPS
'*a,,orr* (s,s)-1
1-,
3ir \
O s O a ,( S , S ) - 1 ,
coHs-.-Z\"uru@#&
OH
"uru*"^r. | OH
" "
(S,S),41olo ee Review of asymmetric dihydroxylation. t-ohray8 has reviewed this reaction, which - rs initiated by criegee's observationin 1936 that pyridine can acceleratethe rate of
240
Osmiumtetmxide-Bis(3-methyl-2,4-pentanedionato)nickel(ID
reaction.As a consequence other tertiaryaminesand diamineswere examinedas catalysts, and were found to also effect enantioselective oxidation of alkenesby Sharplessin 1980. Further searcheventuallyled to bisdihydroquinidineand bisdihydroquinine1,4-ethersof phthalazine.l-ohray and Bhushan(1992) havefound that the bisester(1) of a dicarboxylic acid is an excellentchiral auxiliary for asymmetricdihvdroxvlationof trans-disubstituted alkenes.
CHq
t -
cH.Moe.l
cn/\pnrecHi
'T. Takai, T. Yamada,and T
o ll
Oxalyl chloride (ClC)2. N-AllEl maleinides.t A sha anhydride(l) wirh amines ro fcr thcse products with oxalyl chkrn HCI affords the desiredmaleimrd
F\
o4oAo ' K. B. Sharpless,W. Amberg, Y. L. Bennani, G. A. Crispino,J. Hartung,K.-S. Jeong,H.-L. Kwong, K. Morikawa, Z.-M. Wang, D. Xu, and X.-L. Zhang,J. Org.,57,2168 (1992). 2 L. Wang and K. B. Sharpless, Am. Soc., ll4, 7568 (lgg2). 3 D. Xu, G.A. Crispino, and K. B. Sharpless,ibid., 114,75i0 (1gg2). aT. Hashiyama,K. Morikawa, and K.B. Sharpless,J. Org., 57,5067 (lgg2). s K.-S. Jeong, P. Sjci, and K. B. Sharpless,ktrahedron Letters, 33,3833 (1992). 6 Z.-M. Wang, X.-L. Zhang, K. B. Sharpless,S. C. Sinha, A. Sinha-Bagchi,and E.Keinan,ibid., 33, 6407 (1992). ? T. Oishi and M. Hirama, ibid., 33, 639 (lgg2). 8 B. B. Lohray, Tetahedron: Asymmetry, 3, l3l7 (1gg2).
Osmium tetroxide-Bis(3-methyl-2,4-pentanedionato)nickel(II), OsOa/Ni(mac)2. a-Hydrory ketones.l In the presenceof OsOa (l mol Vol and Ni(mac)2 (3 mol Vo), variousalkenesare oxidized by molecular02 and an aldehyde(usually isobutyraldehyde) to a-hydroxy ketonesin good yield, which can be improved by addition of 2,6-lutidine (2 mol Vo) to suppressepoxidation.
+ CHz:CF
1
o4"A cHl a
3 -A ry I -3,4 -dihy drois oqu i n olint chler-Napieralski reaction,bur rhi isoquinolines.In a modified proccd sith oxalyl chloride to form r.
liminium ion b. This ion cyclizesro hv treatmentwith sulfuric acid in m
i\cl
ll
Oxalyl chloride
h.,: ::r. \\crc examinedascatalysts. r.,: : .,lkcncsby Sharpless in 1980. a:.r ^r\Jihvdroquinine1,4-ethers of h :' '-, l-'iscster (l) of a dicarboxylic h..:- rr lationof rrans-disubstituted
HO\/CH3
02, OsOa,Ni(mac)2 (CH3)2CHCHO, base
QHsI
----
CH3-'\."\
Og.t
ctr---f-otr' o
A2%-
67o/"
o HO. JI -(cHr8cH3 v
CrH" n
o
rT. Takai, T. yamada, and T. Mukaiyama, Chem.Letters, .1499 0991\.
Y-l N' ./
Jo""
o tl
Oxalyl chtoride (ClCt:. N-Allql maleimides.l A short route to these compoundsinvorvesreactionof maleic anhydride (l) with amines to form mareamic acids (2, >95o/o yierd). on treatmentof theseproducts with oxalyl chloride, the hydrochlorides 3 are obtained.Elimination of HCI affords rhe desiredmareimides(4), which arc obtainedin 55-i3vo overail vierd.
/
\
O4OAO 1
ov:\zo cH.cr^ ""'"'! + CHz:CHCH2NH2 I f CH2:CHCH2NH OH 2
. r r 1: r l u n g ,K . - S .J e o n g ,H . - L . K w o n g , . 51. t76u (1992).
II crcococr
+ 0* 2so : ' < r 1 6(71 9 9 2 ) . (1992). r. -r-r..1833 r ' ,-llagchi, andE.Keinan, ibid.,33,
/
on*Ao
\
I
CH2CH=CH2 4
o, n ickel(II), OsOa/Ni(mac)2. | ::,,l .i) and Ni(mac)2(3 mol Vo), Li, r r rlc (usually isobutyraldehyde) g: ,r cd by addition of 2,6-lutidine
,rCl
N(c2Hs)3,25o
*E'2.
r^rrrr o4rAo I
CH2CH=CH2 3
3'Aryl'3,4-dihydroisoquinolines.2 Isoquinorines are generaily preparedby the Bischler-Napieralski reaction,but this crassicar route is not usefur in the case of 3_aryl_ isoquinolines'In a modified procedure,the precursor,(phenyrethyr)amide (r), is treated with oxalyl chloride to form a, which on treatment with Fect3 forms an N-acyliminium ion b. This ion cycrizesto 2, which is convertedinto 3,4-dihydroisoquinorine 3 by treatmentwith surfuricacid in methanor. overat yierdsof 3 are in the ,ung" 55-.s,vo.
Oxazabomlidines
(\1coHs
,.\./.--.,.CoHu
(crco)2
\2 r" o
l
l l
l
I o
\? t'1oAo i
\r''cHo 4-\./,-
:
CHs
+
:
cHo ('1,,,o
-:J
|:':
il I' "' CHsN (92o/"eel
1. :, r rlrne providesthe enantiomerof
9
0
o
o
oArA-Jl.=-"t. :
'B=l
\rn3 1b
+
oAt'l
:
'B=l
eH. CHe
anti, anti - 2b (74V")
CHg 83:17
Under the same conditions,similar anti-selectivealdol reactionsobtain with several other chiral ethyl ketonessuch as 3.4
OxodiPerorlrrll Oxazolidinones, chiral
Asymmetric reduction of ketinirct found to achieve high enantioselecr of ltsuno, preParedfrom BHr and (S derived from (S)-valine,(12'31). is thc Like Corey's oxazaborolidinesderir cd
(c-Hex)2BCl (iHg)zcHcl-lo
o
89%
ezrol)/-cH3 CHg
amounts. The highest enantioseledtr aromatic ketones (as high as 88cr ct of N-t-butylimines of aryl ketones(gl
3
?? "
e,o-?-aYcH'
6H. 6H. cu.
dialkyl ketoneswith 1 resultsin l(l-,
+ Bzlo CH3 CH3
>30:1
anti,anti - 4
srn, anti - 4
cHsl
,CHI
c f----
N'B'o Asymmetricaldolreactions,sThechiralN.propionyloxazolidinone(1),prepared highly -diastereoselective steps from (1R)-(-)-camphorquinone' 'undergoes several in for improving the J'y"utlinity high of uo"uniugt "io)ttlJ aldol reactions with the
H
ilcut'r "o*"i'0,,,,",T:r*:Jl#,1*:*;','I:*:ilffi;:i!i:11?::'.::: Aarru facial preparedbY transmetalatto crystallization'lne oleled of 98-99% after one by (supported with diastereomericpunties (Z)-enolates chelationof intermediate *tin .ot consistent is exhibits also selectivity enolate silyl enol ether)'The lithium an X-ray crystalstructur";;;;;;o;d
r
CoHs
tc(cH3)3 c6H5
cH3
I D. A. Evans, H. P. Ng, J. S. Clark. anJ f, : D. A. Evans, J. S. Clark, R. Metternx-t-
(leeO).
I M. P. Bonnerand E. R. Thornton..{n I r B.T. Cho and Y. S. Chun,Tetrahednt
o
',,*5tt' O
OBzl
(rl) I lt -'--',cHs " + cH.^cHo x{
CHs
-X6 92:8
chiral highlydoubleasymmetricinductiononreactionwith(R)-2.benzyloxypropanol(matching chiral auxiliary provides ttOu"tiut removal of the pair, equation II)' Hydrolytic o' carboxYlic acids or alcohols'
Oxodiperoxymolybdenum (pyridir t lVcdejs reagent.MoOPH). (3R)- or (35) -3-HYdroryas4rtt by hydroxllatitto diastereoselectivity Thus this derivative 1 of L-aspanic I
with MoOPH Providesthe 3-hldror of this hydroxylation is highlv dcg wn-selectivity is obtained with t.}l! THF-HMPA. The highest anti-selcct then with LHMDS in THF.
Oxodipemxymolybdenum(pyridine)(hexamethylphosphoric -- *ex)2BCl
:-,:cHcHo 890./o
CHs lzO
triamide)
Asymmetric reduction of ketimines to sec-amines.4 of the various hydride reagents found to achieve high enantioselectivereduction of ketones, the oxazaborolidine I of ltsuno, prepared from BH3 and (s)-(-)-2-amino-3-methyl-1,1-diphenylbutane-l-ol, derived from (S)-valine,(12,31), is the most effective in terms of asymmetricinduction. Like corey's oxazaborolidinesderived from (S)-proline,I can also be used in catalytic amounts. The highest enantioselectivitiesobtain in reduction of N-phenylimines of aromatic ketones (as high as 88Vo ee). The enantioselectivitiesare lower in the casc of N-t-butyliminesof aryl ketones(80vo ee).Reductionof N-phenyliminesof prochiral dialkyl ketoneswith I results in 10-25% ees.
CH3 CH3 CH3 syn, anti - 4
cH.1
(1), prepared -f ',nr()nvloxazolidinone
tCHs
zCuH, KCuHt Nt^ro D H
. ..rJcrsoes highly diastereoselective -rir crvstallinityfor improving the iu:: rnolate or the titanium enolate,
NC^H^
.-'. r rth aldehydesto form syz-adducts r .:r:tallization. The observedfacial (supportedby r:r:rrcdiale(Z)-enolates alsoexhibits enolate r lithium l-hc :r-,:
a.rr-'Jl.-;r;,
-
:
R
c6Hs,.
o o H
. *"$" CHs
CHg
98-99:2-1
1 , T H F ,3 0 0
98%
H\...NC6H5
cuHu,. crHu (R),87%ee
NC(CH3)3
qH
1
cH3
Ha.NC(CHa)o
cuHu^cH. (R), 80oloee
I D. A. Evans, H. P. Ng, J. S. Clark, and D. L. Rieger, Tetrahedron,4g, 2127 (1gg2\. zD.A. Evans, J . S . C l a r k , R . M e t t e r n i c h ,V . J . N o v a c k , a n d G . S . S h e p p a r dA, m . 5 . c . , l l l ,
g66
( I eeO).
3 M. P. BonnerandE.R. Thornton, Am. Soc.,ll3, 1299(1991). 4 B. T. Cho and Y. S. Chun,Tetrahedron: Asymmetry,3,15U3(1992).
92:8 (matching R r-2-benzyloxypropanol chiral provides rl : :hc chiral auxiliary 1:-
Oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide). (Vedejs reagent,MoOPH). (3R)' or (3s)-3-Hydroxyaspartates.t These amino acids can be prepared in high diastereoselectivityby hydroxylation of the enolate of N-(9-phenylfluorenyl)aspartates. Thus this derivative I of L-asparticacid on treatmentwith a basefollowed by reaction with MooPH provides the 3-hydroxy derivative, syn- and anti-2. The stereoselectivity of this hydroxylation is highly dependenton the base and the solvent. The highest syr-selectivity is obtained with LHMDS, LiN[si(cH1]12, as base in THF-DMpu or THF-HMPA. The highest anti-selectivity is obtained by treatment first with BuLi and then with LHMDS in THF.
Oxygen 1K. Kaneda. S. Haruna. T. Imanaka. \l l|r Letters, 33, 6827 (1992). 2 R. Ramasseul.M. Tavares.and J.-C. \lrctro
Pf=
Oxygen, singlet. Stereoselective photoorygenation of oxygen with allylic alcoholscan shou hr8 tivity. Thus the allylic alcohol (E)-l rer
1) base 2) MoOPH
-^\ -COzCHs CH.OTC- Y I NHPf
OH L-1
l- -cozcHs cH3o2c-Y
+
9H ;- -cozcHs
CHeOzC-
(2S,3R) - 2
(2S,35) - 2
LHMDS,HMPA
95"/"
BuLi, LHMDS,THF
7oo/"
I
NHPf
NHPI
Oxygen -Epoxi'dation.LTheepoxidationofalkenescanbeeffectedwithmolecularoxygen andanaldehyde.Isobutyraldehydeandpivaldehydearethemosteffective.Notethata metalcatalystisnotinvolved.Yieldsarehighestwhentheratioofalkenetoaldehyde is l:3.
+
I
H
o
Hoo' -'r 1o2, ccta Aar" l l - + cHr cH, cH. c ( SS t . i
(E)-1
1 1: 1 1 '.20
R.F. de Boer' and M'P' Alvarez'Tetrahedron rF.J. Sardina,M.M. Paz,E. Fernaridez-Megia, (1992). 463'7 Letters,33,
o6H13ACH2
o
)f
formed with 93 :7 diastereoselectivirI (82: 18) but onll' 31 :6E regioselectivity Photooxygenation of Gc-Gc bt or the azadigermiridine2 with tetraptn peroxides(3 and 4, respectivelv).
h v , 1 O 2 ,T P P ,
02 + (cHs)sccHo!gt#*'gg
Ar2Ge-GeAr2
coHo _ 61"/"
ArzG
1
c.",rX
(cH3)3CCO2H
*+:FaoO^"" O^"" Epoxidationofcholesterol.2Thisreactioncanbeeffectedwith02andisobuin CH2CI2 at room temperature'This tyraldehyde as reductant in quantitative yield I : I mixture. Addition of a (tetraphenylreaction provides the d_ and B-oxides as a porphrinato)nickel(ll)catalystdoesnotaffecttherate,butenhancesp-stereoselectivity
Qa:26).
Ar = C6H3(C2H5)2
H N vtes2ce/-beMes2
F
t\
+sz- Mes2Ge'
o-
Both 3 and 4 are reducedby tnphenll The 1,2-digermetene7 undergocr 1 (DCA) to form the I j dicyanoanthracene
Oxygen,singlet
251
1 K. Kaneda,S. Haruna,T. Imanaka,M. Hamamoto,Y. Nishiyama,and Y. Ishii, Tetrahedron Letters, 33, 682'7(1992). 2R. Ramasseul, M. Tavares,and J.-C. Marchon,J. Chem.Res.(S), 1O4(1992).
t-] ' ,f,
) / Oxygen, singlet. Stereoselectivephotoorygenation of allylic alcohols.t The ene reaction of singlet oxygen with allylic alcoholscan show high regioselectivityand also high diastereoselectivity. Thus the allylic alcohol (E)-1 reactsto form 2 and3 in the ratio 96:4,brtt2 is
9H LC
t,
+
.--- -COzCHs CHqOzC' Y I NHPI (2S' 3R) - 2
I
t'
cH. ro2,ccr4
l l cH.AcH,
-
I """Hoo- -j.f^.H,: f-"r' * a"r' Hoo-
cHs
cHz cHs
3
.rr lloer, and M P' Alvarez'Tetrahedron
oxygen n.. ..rrrbc effectedwith molecular that a Note effective' lc,-.Jc are the most aldehyde to alkene of g:.-' shcn the ratio
t L ^
cHz cHsfigoH
93:7
1:20 Ri
I
(s,R)-2
(s,s)-2
(E)-1
' 11 : 1
OH
OH
OH
OH
formed with 93:7 diastereoselectivity.In contrast, the acetateof (E)-1 shows high (82: 18) but only 32:68 diastereoselectivity. regioselectivity Photooxygenation of Ge-Ge bonds.2 Photooxygenation of the digermirane I or the azadigermiridine2 with tetraphenylporphine(TPP) as sensitizeraffords cyclic peroxides(3 and 4, respectively).
hv, lO2, TPP,
n
clcH2cH2cl,40oc 100%
Rr,celheRr,
.o
t Ar = C.11.16r'nu,,
+
(CHs)sCCOzH
coHo 61%
H N -M ,/\ Mes2ce-GeMes2 2 and isobu2.:. 'r can bc effected with Oz Thb temperature' ir! .: ll] CHrCl2 at room (tetraphenyla of I mixture. Addition -, c\' :'ri ratc. but enhancesB-stereoselectiviq
-9"Ar, Ar2Ge! b-d
t"='l-']"- Ar2Ge'. 'o,GeAr2 e5o/"
a
H (c6H5)3p -GeMes2 MeszGei tr o-o .N.
4
5 H N Mes2Ge( )cetvte",
o 6
Both 3 and 4 are reducedby triphenylphosphineto 5 and 6, respectively. The l,2-digermetene 7 undergoes photooxygenation in the presence of 9,108 in 80% yield. (DCA) to form the 1,2,3,6-dioxadigermine Jicyanoanthracene
oxygen, singl€t-Titanium(IV)
isopropoxide
si(cH3)
hv,1o2,DCA
zCaHs
l-l
/caHu
fu^' +
CHICN/CH2C|2
nrzcelenrz
o-o
Ar2Ge-GeAr2
'qn
(-\
n
\-,
e (3%)
I (80%) 7
si(cH3)3
tr-Aar. acids'3 Reaction of pyrrole-2of pyrrole-2-carboxylic water Oxidative decarboxylation in i-ProH or cH3cN and I and 2 with singlet oxygen as such acids carboxylic in high yield' (3: 1) results in 5-hydroxy-3-pyrrolin-2-ones
cHs
,cH.
/ \ \ CH3OOC--\*'^-cOon
1oz, (cH3)2cHoH/H20 ( 3 :1 ) ,
83"/"
cHs FH" /-\
cH3ooc*.,Ao H O T
I
r W. Adam and M. Richter,Tetrahedron l cttct
Ozone. Oxidation of RICH(OH)SiRJ to R'C( lanes are oxidized by ozone to the corrcrF attachedto silicon is an allyl group'
CHs
CHg
3
1
OH -,,\-si1cH.;rcH2cH:Cll2 csHtt-
CH30. CHsO.
'Oz'
H
/// \ \\\
cH3ooc--\*'^cooH
cH3cN/H20 ( 3 :1 ) .
92"/"
I
CHs
/-\
cH3ooc*.,Ao HO 'f CHs
o
-,\il -si(cH3)3 csH.r(
4 This reaction can be used to con\cn
1) BuqSnLi
6549 (1992)' I W. Adam and B' Nestler' Am' Soc'' f 14' cl\'.911m''
45't'4s8(1ee2)' ."0 *. o"J",l' i s 2M. Kako,r. Akasaka, (1ee1)' ' l' org, s6' 6e42 t ;.;.;;;"; "'tl c M' Baldino isopropoxide'15' 322' Oxygen,singlet-Titanium(IV) of vinvlsilanesin the presa"ntt', Vinylsilanes- sil)l ))""t ,t1t::::tt*ttion iigrt regio-anddiastereoselectivity' *ilvr epoxyalcohols*itr, p-silyl enceof Ti(o-i-pr)+ "tr-a. *ittt O' to providea first step an tnt '"u"'tn the as involves The conversion undergoesepoxidation' "Urtn """nt, which then
CHO
zi (ci.).sicN 3) BuLi
-------------.-79/o
-v
3-Atkoxy-1'alkenes - aatkort al in the presence of CH3OHNaOH' Prcs convertedinto a dimethyl acetal. rrhich reaction with ozone.
'U
si(cH3)3
v - |
t :
GeA12
o
a
,tcaHs
n12eelenr2
102, Ti(O-l-Pr)4
Ozone
7Oo/o
e (3%)
?.
si(cH3)3 Bu-.rZ\cHs
(cH3)3si, _o
-
"o)-!
59o/o
:'lic acids.3 Reactionof pyrrole-2water :cr rn i-PrOH or CHrCN and t h r r el d .
Bu I W. Adam and M. Richter,Tetrahedron Letters,33,3461 (1992).
cH3\-JcH3 t:l
""oo;o/Fo
Ozone. Oxidation of Rt CH@H)SiRj to Rl COOH.t a-Hydroxytrialkylsilanes and acylsilanesare oxidized by ozone to the correspondingcarboxylic acids,even when one group attachedto silicon is an allyl group.
CHg 3
OH |
crH'
--
1) os 2) s(cH3)2
c5H11co2H
81"/"-
si(cH3)2cH2cH:cH2
cH3O\---
{
"t'oor"o#o CHs
o crH,,,Asi(cHs)s
4
This reaction can be used to convert aldehydesto acids.
OH i ', t-:
-r57,458(1992)'
tr..
cHoll BuLi 3fr1,1'","3)
i
797o
pres".r *..otion of vinylsilanesin the diastereoselectivity' and n::. hrgh regioi ::.1!tronwith 02 to provide a B-silyl )c
os
nYsi(CH3)3 V
l
|
i
8oo/"
6\COOH l
|
\/
3-Alkory-1-alkenes - a-alkox! esters.2 This conversion can be effected by ozone in the presenceof CH3OH,I{aOH. Presumablyan intermediatea-alkoxy aldehyde is convertedinto a dimethyl acetal, which is convertedto the a-alkoxy ester by further reaction with ozone.
OBzl
c6^r")"'zcHz
U3
oBzr i,i:,jii ---.---------* cuH,,sAcHo
OBzl ,.. -o-Na* CoHrsI ocH3
za./" I o.
I
OBzl
I
c6H13^co2cH3
OBzl
Palladium(II) acetate. Cyclimtion of 4,6- and 5,74icnea 3) cyclize in the presenceof pd(OAcl: and indolizidinone 4, respectivell..in g
cH/"z\(cHr^col l,n=2
-SrlBi,?Ba-*coocH3 -
----rs%
(, 3.n-
cHsozc(cHz)6co2cH3 75o/o
I R.J. Linderman and K. Chen, Tetrahedron Letters, 33' 6'167 (1992)' 2J.A. Marshall, A.W. Garofalo, and R.C. Sedrani' Synlett, 643 (7992)'
Oxaspirocyclic addition to I J4icr, with p-benzoquinonein acetone-:rrtrc in a spirocyclic ether 2, formed bu an r addition of the oxygen function can tr which results in the spirocyclic erhcr J
.Y
99% cis)
rc-
oBzl
{.--
I
,, ,.)-.--.O-ttta-
\.6n 13
|
OCH3 78YoI o"
I
OBzl
I
C5H13
Palladium(ID acetate. Cyclization of 4,6- and 5,7-dieneamides.l (ct., 16,261). These dieneamides(l and 3) cyclize in the presenceof Pd(OAc)2 and an oxidant (CuCl2/Or) to pyrrolizidinone2 and indolizidinone 4, respectively,in 85-90Vo yield.
CO2CH3
1-r'\ \-tf(
Pd(OAc)2,THF
OBzl
cHl'4(cH2)ncoNH,
**#g
1,n=2
2
O-coocH3 3, n=3
---------------85o/"
trl -*\,
F1.O2C(CH2)6CO2CH3
6 - ' - Ll ( ) 9 2 ) . -- ':1 (1992).
o
4
o
Oxaspirocyclic addition to l,3-dienes.2 Pd(II) catalyzed oxidation of the diene I with p-benzoquinonein acetone-aceticacid in the presenceof a base, Li2CO3, results in a spirocyclic ether 2, formed by an overall trans-addition to the diene. Overall cisaddition of the oxygen function can be effected by replacementof Li2COr by LiCl, which results in the spirocyclic ether 3.
(CH2)3OH
q-)
Pd(oAc)2, [o] HOAo,Li2CO3
^,.-/
860/o
AcO2 (>960/otrans) I
73"7.I I t
Pd(OAc)2, [Ol r-icr
o1 /\/
t
cl ,.'\/
l
3 (>99% cts)
Palladium(II)
ac€tate
Methyl enol ethers readily RCH2CHO - RCH:CHOCHj - RCH:CHCHO'3 prepared by reaction of aldehydes with (methyloxymethylene)triphenylphosphorane, and then with NaHCOT [(C6H5)3P:CHOCH3], when treatedwith Pd(OAc)z in CH:CN 'H2O (1 equiv.) are convertedinto a, B-unsaturatedaldehydes' and Cu(OAc)2
Pd(OAc)2,NaHCOg
tffittHo -srt C6Hs(CHs)aCH=CHOCHs c6Hs(cH3)4c
J CH.PTf "\K
z ,a d
t
)
+ H2c^cH2os I
-H
f'^Yott. cHz"''a
cHr
caHsN
ajt'^
c6H5(cH3)4cH=cHCHO
CaHsN Heck cyclization.a A short, efficient, and asymmetric synthesis of the anticancer (4) involvesN-alkylationof the optically activehydroxylactone alkaloid (S)-camptothecin 1 with the bromoquinoline2 to provide 3. This product undergoesHeck cyclization to the alkaloid 4 in 59% Yield.
Coupling of vinyl halides with oIIvinyl halides with allylic alcohols unJc mixture of products.Addition of silrer cr in a palladium-catalyzedcoupling of rrnr a y,6-enal, with retentionof confieur.ri
CHr:666"rO"
Et
Pd(ClAcll
&.rrt*rSO. KOC(CH3)3 DME
87"/"
rY*Y'' \,,'\Z\z
i
/-\ coHrs
I
Palladium-catalyzed coupling of a r rn presenceof silver acetateor carbonarcn configurationof the vinyl halide.
1 , c r 6+ 1 0 5 o
OH
cHtsAcrH,.,
A
CoHrs (S)-4,crp+42o
Heck-type coupling of allylic alcohols and enol triflates.5 This vinylation of allylic alcohols can be effectedby catalysiswith Pd(OAc)z and tri-o{olylphosphine (l:2) and triethylamine (excess) as base. The major products are conjugated dienols.
^tr
I
Arylation of allylic alcohok." ..\^t :rpe reactionto form p-aryl-a,p-unsarun P(CoHs): as catalysts and I equir'. of , :ompounds. Reaction of aryl iodides and allrlic r :ransferconditions(NaHCO:/BurNCl ) rcs
Palladium(II)
:H()
oTf
MethYl enol ethers readilY
rr r rr r t hvlene)triphenylphosphorane, r: ( I{.CN and then with NaHCO: r. r
Pd(OAc)2,Ar3P -t-\
+ H2C''
N(C2H5)3, DMF -CH2OH ---r"*-
Pd(OAc)2,NaHCO3 Cu(OAc)zHzO
= C H O C H g- -
,r%-
-r- cH"pH=cHcH2oH K cJr
-l
f
t
t a. 2 "/ COOCzHs
A a -;** m+ O a ol1:f" ,$-\" ,$-\" qv,
.:(
.:(
I R. Grigg,A. Teasdale, andV. Sridharan, Tetrahedron Letters,32,3859(1991). I l r / , rrt'r.t,32' 3855 (1991). rt: [
,..,J\N-\-,,
n'lf,r".fi. o (R)4
I t,^.r Jzrrto
7
s$'
o
o o H
Pr
(+)-8
NaOCH3,CH3OH
Pr
)-.-z\ t
l
D(+)-9
Rl .,cooH
fi|tt"ot' (R)-2
(S)-Phenylalanine dimethylamide
273
' D. L. Comins and H. Hong, Am. Soc., ll3, 6672 (1991). .
--F. -78'
-CaHs 65't
(S)-Phenylalanine dimethylamide, -HzN^,J,.,,r,"r.,,
(1)
y o
r.
* " ,
o .\.s'1i-e4. l l l
,t'-lt-
{.
\--J
5 .r rlhcsis of the alkaloids (+)c .:r'rrroof 5 reactswith dimethylr',- i). Desilylation(oxalic acid, rJ:' 7. The dimethYlamidegrouP I I ..,tulyzedby CeCl3(2'5 equiv.) )l{ rn CHIOH Provides(+)-9 in
(R)- and (S)-a,a-Disubstituted a-amino acids.t Although only a few a-amino acids of this type are known, they are present in some microbial peptide antibiotics. A number of routes are known to racemic or to one enantiomerof amino acids of this type, but the most practical route to both enantiomersappearsto be resolutionof racemic N-acylatedderivativesof these acids by a chiral amide containingone or two (S)-phenylalanineresidues.The diastereomersobtained in this way can be separated by crystallizationor by flash chromatographyon silica gel. Thus the racemic amino acid (2) is converted to the 1,3-oxazol-5(41{)-one(3) by an activating agent such as 1,l/-carbonyldiimidizole(cDI), which without isolation is coupled with the chiral amine I (DMF, 50) to form two diastereomericdipeptides (4) which are separated by crystallizationor chromatographyon silica gel. Several methods are available for cleaving the chiral amide, but the most useful is reactionwith cFrSo.H in cH.oH at 80' (SchemeI).
tl
o si(i-P03
I
o
cDl | -.---_
-coo'r
IRl--J
*ltt"ot3
)-o
\
I nr'trrr^n'
2
3
6(97:3) )H
t
PrMgCl, CeCl3
cH2c6Hs
?
O
tlA*\N(cH3)2
Rr' fiHcJil. o
Rrl NHcJl3 o
(R)-4
(s)-4
I 1)Ac,o.A I 2) H3O+ I
\ "-
:,
\ N-
I
CH2C6H5
t'>,""'(I\N(cH3)2
Rl .,cooH l|*t.o*3
I lir.cooH "'runcon'', .' i/
* 1
(R)-2
(s)-2 SchemeI
274
(1S,2R)-(+)-Phenylcyclohexanol
In some cases,better Iesultswere obtainedby use of l-phenylalanyl-l-phenylalanine dimethylamide in place of l. I D. Obrecht,c. Spiegler,p. Schonholger, K. Miiller, H. Heimgartner,and F. Stierli,Helv., 75, 1666 (1992). (1s,2R)-(+)-Phenylcyclohex anol (13,244; 14,128- 129, 16,113 114) (l)' use as chiral auxiliury. whitesellr has reviewed use of this chiral alcohol One particularly as comparedwith that of (-)-menthol and (1R)-(+)-8-phenylmenthol' of trans-2-phenylresolution by available I are of enantiomers both is that advantage 2-substituted cyclohexanol by means of enzymatic hydrolysis of the esters and that originally was used auxiliary this chiral Although available. readily are cyclohexanols of alkylation for asymmetric useful is also it glyoxylates, of reactions of ene for control enolates,and for control of various cycloaddition reactions' The reaction of a chiral vinyl ether (2) Asymmetric t4+2llt3+2lcycloailditions.2 adduct (a) and a nitroalkene (l) catalyzed by a Lewis acid results in an intermediate and (-)which undergoesan intramolecular [3+2]cycloaddition. Both (*)-camphor have been used as the chiral auxiliary. Thus the vinyl ether (2) trans-2-phenylhexanol Hydrogenation formed from the latter auxiliary reacts with I to give 3 in 737o yield. 4, in which lactam a-hydroxy tricyclic a provides and auxiliary chiral the cleaves
Noz
"r.\-JJ-coocH3
^ rt"-R* + l l CHz
Cl2Ti(O-l-P02 cHzcl2'-90"
:"""'l 2
730/o
cH3ooc
H2 RaneyNi I O-/o
H (1S)- 4' 98%ee
Clhasthe(S)-configuration.Ifthereactionofl.and2iscatalyzedbymethylaluminum MAPh, (1R)-4 is obtained in 797o ee' Surprisingly' use of bis(2,6-diphenylphenoxide), MAD' provides (1S)-a in 75% methylaluminum bis(2,6-di-r-butyl-4-methylphenoxide)' can also be ee. when (*)-camphor rs used as the chiral auxiliary, the enantioselectivity
controlled by the choice of lru is xr ee, and Cl2Ti(O-l-Pr)2provides ( ISF
the Lewis acid catalyst can be as effc Chiral a -methyle ne-y -but-vrfua y-butyrolactonessuch as 7 utilizcs tlx 1,l-dibromohexane andZn-TiCl,' T! reactswith dichloroketene to form thc 4 followed by oxidation with chromr (+)-5. Hydrogenationand oxidation p final stepinvolves introductionof a rn< a naturalantitumorantibiotic.
C6Hs,,../,^\
I c6Hsocory
l + Q H ' 2
( Z \ - 3 + C 't " C = C = .o! ^ 65-79a
1) H2,Pd/C 2) RuCl3,NalOa 3) cH2N2 _ 61oloOv€rdll
o
aP
Hooc"lr
( - )- 6
3 -H y dro xy -4 -phe ny l- p -lactans -' couplewith the N-(trimethylsilrl)im .tcreoselectivitydependsin part on c'stergroup. Use of either (+1- or r .ruxiliary results entirely in a as-p-l r -)-menthyl or of Oppolzer'so-i-.97\
cbl
2603(leeo).
aP.D.Bailey,R.D.wilson,andG,R.Brown,J.C.S.PerkinI,1337(1991). ;lcaves the C-O
(S)-PhenYlglYcine. The organozinc reagents deAsymmetric synthesisof a'methylene-y-lactams'r a-methylene-7-lactams' form react with imines to rived from 2_(bromomethyrju".yrut". provides theseproducts imine chiral auxiliary for the Use of (S)-1-phenylglycineas the in )95Vo ee.
bond and also redut-rr
:ransfer hydrogenolysis provides the l-suh
Reduction of 2 with triethvlsilanc catr bond to give 5 in >94% de. This pn
t'-O
t'nfortunately the chiral auxilian
is n<x n
(R)-(-)-2-Phenytglycinot (l)
cooc2H5 +
BrZn=_-\CHz
C6H5C=NH \ -.COOC2H5 rHF,20 30' go-esz I CoHs
//FHz
I
Bzl
cuHu4lrAo m. :hr lpipecolicacid (equationII). and ethyl lR ,-l-phcnylethylamine :; ) n 447oyield and TOVode.This h. . hiralauxiliaryto ethyl (2S,4R)gives t R r-l with cyclopentadiene
cuHu
+ c2H5oZnBr cooc2H5
(>95% ee)
'Y.A.
Demb6l6,c. Beland,P. Hitchcock, and J. vlrieras, Tetrahedron:Asymmetry,3,35r (rgg2).
(R)-(-)-2-Phenylglycinot (t), tS,2S6 Asymmetricsynthesisof pynolidines and pyrrolinones.t This chiral B-hydroxyamine(l) reactswith a 7-ketoacidin refluxingtolueneto form a chiralbicycliclactam 2 in 75-98% yield.Treatment of 2 with excessalane,generated fromAlcl.r andLiAlHa,
,,,.fl:oo""' 2 (7oo/ode)
9t'
OH ( \'-NHz -: CoHs
R
-
I
I
-NAcoocrHu
r ' ll37 (1991).
'l-he organozincreagentsdeLr. :".:' tirrm a-methylene-7-lactams. :..i imine providestheseproducts
75 - 9go/o
R, AtH3
i' I )eclercq,TetrahedronLetters,,31,
to.-, ll o
c6HscH3 A, -H2O
(R)-1
H (25,43)- 3
r-..,:,Jron: Asymmetry,3, 459 (1,992).
"^
75 - gso/"
HO
\.rru--z :
HCOONH4 Pd/c 60 - 7go/o
R1.,
HNJ
6uH, 3 (>97o/" de)
cleaves the c-o bond and also reducesthe carbonyl group to provide 3, which on transfer hydrogenolysisprovides the l-substitutedpyrrolidine 4. Reduction of 2 with triethylsilane catalyzedby Ticla effects only cleavageof the c-o bond to give 5 in )94o/o de. This product is reducedto the lactam 6 by Li/NHr. Unfortunatelythe chiral auxiliary is not recovered.
Phenyliodine(IIf
diacetate- Iodine
(CzHs)gSiH Ticl4 -t
a3 - 94"/"
>
*" Hq a\
R
w*{
Li/NHg CzHsOH 65 - 93%
CHr
,
oHil-
/--\
r*\/
.r^! l
l
t2 c6H5t(oAc)2. h v
l
tl
6uHuo
o
| ,^ l
-"-
l
cHs
t
6
5
|
1
r L. E. Burgessand A. I. Meyers,J' Org ' 57' 1656(1992)'
Phenyliodine(tll) diacetate, CcHsl(OAc)z' I with Oxidation of an N-protected tyrosine Oxidation of N-protecteil tyrosine't by treatment a spirolactone(2)' which is converted C6H5I(OAc)2in methanol p'ouid"' common to system bicyclic a 3' exo-hydroindole with NaHCO3 in CHrOH into the of can be converteddirectly into 3 by oxidation various Stemonaalkaloids.Actually 1 linthepresenceofsodiumbicarbonate.Theconversionoflto3evident|yinvolves intramolecular by a highly diastereoselective para-hydroxylationof u ph"nol followed
2 --^, "-"fI N"Hco.
l--\
HO-
p-CH3C6HaMgBr
t\N*'i l
2
1
oH
1) NaOCH3 2) (HOOC)2 88k from 1
CeCl3 1)NaBHa. 2 ) M s c lD , MAP _ 58"2.
I W.J. Richter, Ber., 117,2328(l9rr{r r J.M. Bruneli,O. Pardigon, B. Faurc.ad
N-(Phenylseleneno)phthalimide. Cyclizttion of hommUybc akol cyclization can be effected*ith alnrc with Nicolaou's reagentl. The prtrdr tetrahydrofurans.
l r l
P-CH3C6Ha\"'-TCO2R*
I
CO2R*
for reduction of ketonesby ditnranc Highest enantioselectivityobtains frtrr methyl ketone is reducedwith 9l-r c Use of 1 equiv. of 2 permits reducti<x ee. This oxazaphospholidineresembl
r rscr CHP"
CHa-.-..A.r_r,,,:-rra. I
H
bore=t
3
4
93% ee.
F.A. Davis,R.T. Reddy,andR.E. Reddr..I (}l
nrlrndtDe
(+)- or (-)-(N-Phenylsulfonyl-3,3-dichlorncamphoryl)oxaziridine
o. j' cuHu-s-N4c6H,
'.
),
CHl'
oLi I
-OCH3
(-)-2
r ^"- ;tlccted by conversionof an c:: - .) a hydrogen atom donor c:':. ,rcd as the intermediatebut
oV
a:::.1rc'dbv reactionof a phenol d r - rhc reduction,but the most t ,- rniriaror,AIBN or dibenzoyl
-78"
Ei%-
oV a
c^H.-s-NH * t C6Hs"\--,-CoocH3
il.r ;';.por.6 by acylationof the
285
coHs/"-NH : coHs&coocH3 s0:10 (3R)-3
(3S)-3 7a- Bso/of cr.coo*, c".o"
t
NHz
t
c6H5-A-"-coocH3 (3S)_4,>95% ee .-'
a:r
c6HssiH3 cnHscoo), 8,- 10o.,"
RH
p-amino acid 4. Note that the enolate of a B-amino acid such as (3R)_6 is oxidized by the (10_
,r.)l).
CHr-._.-Ctta /\ _/,\__
r f ,rrraziridine(l), 16,119-lZO. irntnes; p-amino acids.t This ir.-r. r in CCIa in 8O-9OVoyield
/-t-Z
(^)N D c i O2 (+)-5
?u"u oAruH = coHs*coocH3 \^
(3R) - 6
t't4CuHu I
lr ,irirc p-amino acids. Thus r, i{. r-2 affords sulfinamides3, in-.r hv hydrolysisinto the (S)_
?ut' 1) LDA 2) (+)-5
OAtrtH :
-7 (sY") + (2s,3s) coHs-^)icooCH3 : OH ( 2 R , 3_S7) ( 4 9 V' o uu,,0
camphorylsulfonyl)oxaziridine(+)-5 to the syn-a-hyd roxy-B-benzoylaminoacid 7 in 49Vo yield with >93Vo ee. 'F.A. Davis, R.T. Reddy,andR.E. Reddy,J. Org., 57,6387(1,gg
.
286
(Phenylthio)methyl
azide
(1' azide, (azidomethylphenyl sulfide)' C6HsSCH2N3 l0'14)' (Phenytthio)methyl ' (+)-mitomycin A key step in a total synthesisof the alkaloid i-UrrnyUriri.dines.t K(7)istheintroductionoftheN-methylaziridinering,whichwaseffectedwiththis triazoline 3 in 9OVoyield' reagent. Thus 1 adds to the imide 2 at 80' to give the of the triazoline group After elimination of the carbonyl group to form 4, irradiation
cH39 o cH3o.--,\--4 PCH3,cHzscoHs
1.coHo,8o. ,
ll | >__,-_N: so"/. cr",'-yo-*l-_1._(,*
cH3o
r> \*At
I O'.,r,'CH2CH2CoH5
1, h\' cH2c,,2 -+0 L - 5 '
tl
2
I severat I steps
i D. H. R. Barton,J.C. Jaszberenli. arrJI
cHsQ t o
NCH3
RCOOH - EHNz.t Ac1'l &n 14,268) when photolyzed in the Prcv I to form the imine 3. These imirrs to primary amines (4).
o
{ 3
1) hv, C6H6(+8"/")CH3O 2) Raney Ni (70ol.)
3-Phenyl-3- (trifl uorometby! )dirrir
9CHs,CHzSCoHs - - N
//N N
cH3o
Phosphazenium fluoride (l). Preparation:
1) (Ctrt/ 3)'gj (ct3P=N+=PCt3)PCt6-
CH3O 5 (eoo/.) | ,1 1"*ry.r,"*2Li
(76"/.) As(r) l2) cH2si(cH3)3 CH30
,OH
PyHOTt lJn2Vt2
81%
CHg
I cH3o--.\'{
ll
cHc .ocHs
The value of this salt is that it i .hould be as useful as (CHr)rN-Frn THF at 25' in 93Va Yield.'
ll r='
CH.,,/Y'*N\,-DNCH3 o (r)-7
c6H55O2O (48Voyield),which is reducedby Raneynickel to resultsin a (phenylthio)methylaziridine conversionof the keto group at an N-methylaziridine(5). Remainingstepsto 7 involved precursorto (+)-mitomycin Ce to methyleneand oxidation to a quinone6, the immediate K (7). Angew.Chem.Int. Ed'' 31,915 (1992)' 1J.W. Benbow,G.K. Schulte,andS.J. Danishefsky,
2
R. Schwesinger,R. Link, G. Thick Chem. Int. Ed., 30, 13'72(1991\.
Phosphaz€niumfluoride (1).
\ - . : : . i c ) .C 6 H s S C H 2 N(31 ' 1 0 , 1 4 ) . sr :::rr.is of the alkaloid(+)-mitomycin h:- :rng. which was effected with this r' ir.i the triazoline3 in 907a yield' r: {. rrradiationof the triazoline group
CH3O
O
rc
PCHg ,CHzSCoHs N //- N N
l.
cH30
--\
,oCHerCHzSCoHs
//N
cH30
r\ i l
\trtAs
l
I O\y..CH2CH2C6H5
1, hv
cH2ct2
cF"
o-5" ' c6HscH2cH2N
rl Raney nickel. Reductive N-N cleavage of hydrazines. A diastereoselectivesynthesis of chiral a-amino aldehydes(4) from glyoxal involves an intermediatedimethylhydrazone(l), which reactswith an alkyllithium to provide an a-substitutedN/,N/-dimethylhydrazine (2). The mildest method for cleavage of hydrazinesto primary amines (3) involves hydrogenolysiscatalyzed by Raney nickel at 30-50'. This Raney nickel reductive cleavageis markedly improved by sonicationand proceedsat atmosphericpressureof
cH3"*oH
{
CHq
t cH.#oH
l
CHr
-
H2 at 20' in CHrOH in yields of 66-847o with no racemizationor debenyzlation.r 1) H2NN(CH3)2
coHj ,coHs t'""."rn*""*.
ocH-cHo
coHs\_\
FHs
1) RLi
2l Hzo
|\N' /-\ \N1cHr;t cuHuu" CHs
Oxidation of chiral ketals.: Thc chrnl ro 2-hydroxyketal 2 with high (>99:l t cn proceedvia a perrhenateesterof a l-hr.Jro cther3 is oxidizedto the 2-hvdroxr kctal . comparableyield.
cH3,.
,cHt
1
coHs\-\
,CHS
F
coHsl-r.i.
HzlNi
"^r^'.'frlNN(CH3)2
,CHS
CHs
bH.
I
/R
cuHr"'(r'ftH,
66 - 84%
o.t/o .-\ I \.,.
Re:G
I
1
1) (Boc)2O 2l HCl2o/"
O R \ \ /
a-\
H
NHBoc
4 I A. Alexakis,N. Lensen,and P. Mangeney, Leuers,32,1171(1991);idem,Synleu, Tetrahedron 625 (1991\.
Rhenium(Vll) oxide, Re2O7. Oxidative cyclization of S-hydroxy alkenes.t Reaction of these substrates with Re2O7and a base (preferably 2,6-lutidine) in cHzclz at 25'provides 2-hydroxytetra-
^" l Bi:,^ J cHt.
,cHt
o'ro" ReP-
/'\ (, 3 I R. M. Kennedy and S. Tang, Tetrohedrtn : S. Tang and R.M. Kennedy, Tetrahedm
I cttt ltor
Rhenium(VII)
oxide
hydrofurans.Theseproductscould be formed by dihydroxylationfollowed by cyclization. And indeed the product in the first example is also obtained by epoxidation of the (Z)-isomer of this alkene followed by cyclizatron.
rc:. '.clcctivesynthesisof chiral (1), rrr, Jratc dimethylhydrazone \: i : .r:cd Nt,N/-dimethylhydrazine t, :rimary amines (3) involves r' I his Raney nickel reductive :.!.r\ iit atmosPhericPressureof
9Hs
9Hs
.H A.,^\.A
ou
----azu*
Ho.
"f,|)o^"t. (trans/cis= 33: 1)
e - : r z . r r i oonr d e b e n y z l a t i o n . l
CH: t.
1) RLi 2\ l12O
--\
N
NN(CH3)2 CH:
oxidation of chiral ketals.2 The chiral ketal I is oxidizedby Re207and 2,6-lutidinc to 2-hydroxy ketal 2 with high (>99:1) enantioselectivity.This reaction is believed to proceedvia a perrhenateester of a 2-hydroxy enol ether, since the 2-hydroxyethylenol ether 3 is oxidized to the 2-hydroxy kctal 2 by Re2O7in similar enantioselectivityand comparableyield.
cHs,.
CHs
cHs
,cHt
1
FH' c-r' 1-Nr /R (*|a*r, C-H..
fl
,cHs
o-.r,'o
I
Re2O7, base
(, (S)-2 (>99:1)
1
t'crsi(cH3)3 ""'' I 2) Bu4NF I
cHr.
,cH, o.'l oH
lBoc
-12. I171 (7991); idem, SYnlett, .t\
a
-)
*",o,.0"""
84"/"
\_/ 3 lr.,.irrrn of these substrateswith - .': 15" provides 2-hYdroxYtetra-
I R. M. Kennedy and S. Tang, Tetrahedron Letters, 33, 3'729 (1992) 2 S. Tang and R. M. Kennedy, Tetrahedron Letters, 33,7823 (1992).
2g8
Rhoilium(ll) carboxylates
*"1#i;t1,.:"'1".:t"1il:'
osi(cH3)3
(1) with 1-T,::h"..y11:ltrimethvrof vinyrdiazomethanes.
'#':l: i"ffi i,ior*".*o-*,:."f ti;';f ;*::*:IT,"l::*::"ffi
silyloxy)butadiene(2)catury'eouy,,t'ooiu-1tt)acetateorrhodium(ll)pivalateresultsin
(3). Short exPosureor :
I 4-ocs" (r)
CHz .' N 2 VCHs
+
791" ee Am' Soc"ll3' I M.p. Doyle,R.J. Pieters, S.F. Martin,R.E. Austin,C'J. Oalmann'andP' Miiller' 1 4 2 3( 1 e e 1 ) . (1992)' 2 M. N. Protopopova, M. P. Doyle,P Miiller,andD' Ene'ibid" ll4' 2'755 Letters,33, and K.L. Danidr,Tetrahedron 3M.P. Doyle,u.N. r,otopopouu, w.n. Winchester, 7819 (1e92\. aS.F. Martin,C.J. Oalmann, andS' Liras,ibid,33' 672'7(1992)'
Ruthenium(IV) dioxide, RuOz' (2 equiv') in a TFA/TFAA medium is Oxidative phenolic coupling.t RuOz'2HzO I to afford the lignan prostegoneA (2) an excellentreagent fo, po,o-po'o coupling of in80%yield.SubstitutionofRuo2byTl2olalsoconvertslinto2,buttheyieldis45To.
RuO22H2O BFgO(CzHs)z cH2cl2
.\o
T1IFryq* 80/o
I M. Takahashi,Y. Moritani, T. Ogiku. H ()htr
33, s103(lee2).
rJ.-P. Robin and Y. Landais, Tetrahedron,4S'819 (1992)
Samarium/Methylene iodide (ll.l-5 t. Cyclopropanation of viny lorgand tion of allylic alcohols substitutedhr srlr selectivity particularly when carried oul r
,sg- rl1 to N-(l-butyl)-4-ethoxy-2-
a't
D h:O -Kz'\N-C(CH3)3
\ --\ /
Salicyl alcohol (2-hydroxybenzyl alcohol). Unsymmetrical biphenyls.t This alcohol can be used as a template for synthesis of unsymmetricalbiphenyls with substituentsat ortho-positionsby an intramolecular Ullmann coupling.The two esterbondsof the coupling productcan be cleavedselectively
'o
3.78"/oE@ c duJtacetates.a In the Presence h--::\, asvmmetric intramolecular n
by NaOCH3 or a primary amide.
"tr? cH3ol.,o]
\rll' h eC.
+
6'\"\0H
\A*
*
/\ i l l *or/t(tcoct
f\cocr
7s%-
I
o ): '- ,nn. and P. Miiller, Am. Soc.' ll3, | : l l { . 2 7 5 5( 1 9 9 2 ) . h i Daniel, Tetrahedron Letters, 33' r .,1r
r.Yoffiocn" \z\o
,r.,,,,.$ocH,
o
UU DMF. A
9O"/o
Noz
860lo ruaocns
medium is c-.-r,. ) in a TF{TFAA ,:J thc lignan Prostegone A (2) i:: L r- : : . I i n t o 2 , b u t t h e Y i e l d i s 4 5 V o .
lr,O
|
ocH3
o .\o
r'\r'-\oH + 9o,
ocH3
H.O I M. Takahashi,Y. Moritani, T. Ogiku, H. Ohmizu, K. Kondo, and T. Iwasaki, TetrahedronLetters,
33, s103(lee2). Samarium/Methylene iodide (14,275). Cyclopropanation of vinylorganometallic compounds.r Molander cyclopropanation of allylic alcohols substitutedby silyl or stannyl groups can show high diastereoselectivity particularly when carried out with a large excessof the samarium reagent.
306
Samarium(O)/Samarium(Il)
iodide
The diastereoselectivityof an (E)-vinylsilane (1) depends on the steric bulk of the R group (equationI). Higher diastereoselectivityobtains in the cyclopropanationof a (Z)-vinylsilane (2), and is not affected by size of the R group (equation II). H I ( l ) ( C H s ) s S i)
-
uR
l
H
l
O
(cH3)3si. H
* *
H
81% 46:1 76o7o1:1O
H
t (cH3)3si oH
7
rA. Ogawa,N. Takami,M. Sekiguchi. I Rr1 (1992\.
1 a ,R = c - C o H r r lb, R = CHg
(ll)
9^Snt n+
(CHs)sSi'
H
,H"/'\rR , | ^
coHscoN(czHs)z
-
H-A-'n(cHs)ssi-*?R t l oH
H -n . . H ^
* 1cH.;rsi.--*-y't
OH
670/0 >1OOt100:l-a -r+ O 71
(=(-t"' \/
o
I
\-zf--,2 l
84cb
This Barbier-typereaction *ith ('ll-l cyclopropanols. Highest yields of xrlt CHzIzlSmIz-- 1:3:2.
CHs
,/--n, ( l F o
THF 25
ra*a
CHzEt
O -
\/
a-'(o t l
1 L } 2l Cxr: Sr. 55'a
Cyclization of allqnyl halidcs: retlll Bu3SnHfor cyclizationof 6-halo-l-rrrr g with DMPU as a cosolvent with THF
Samarium(II)
-\r1
/cH"
t l-N
(CH3)3CCOCl+ CHgCHzCHO
o It
2 Sml2
(cH3)3c-
64o/"
/
iodide
-cHzcHt Y OH
H
/
CHlr
-
r-\
In the presence of Sml2, benzyl Addition of CICHzOCHzC6H5 to )C:O.o chloromethyl ether adds to carbonyl compoundsto effect benzyloxymethylation'These adductson hydrogenolysisprovide l,2-diols.
,.\o
o .r 'nc I on treatmentwith Sml2 u:.lJrgocs reductive cyclization to :h :rJuctive cYclizationshave been
c6H13
cH3
Ho..
rHF.25. rcHs ---u*----* cur" t!o-"'"c6H5 crcHrolnrcu'u
rcaction is that it Proceeds
\lrl
This Barbier-type reaction with cHzlz can be used to obtain iodohydrins and cyclopropanols. Highest yields of iodohydrins obtain when the ratio of kctone/ CHzIzlSmIz: 1:3:2. "
H.
7oo'o
?
f^a^ F - : F I O
smt2, cH2t2,
tot/ttt
,
-cHs---7E-U rHFo" ' 25'
U
?
smt2, cH2t2,
?t
fff.H,e,.-fffa=av v \ 2 )s R3
r,"tl,l,?t',,/-\-oH a'-'150:1)
(2 equiv') can effect cyclization of the Vinylogous Barbier reaction'a SmI2 DMPU (or HMPA) to give a bicYclic unsaturatediodo ketone I in THF containing by an aldol reaction' samarium enolate (a) that can be trapped
Reduction of fiJN02.to Priman' \'\1r duced by SmIz with CH3OH as thc Jrtrtn amines depending on the amount of Sml; in THF/CH:OH (2:1) for less than hrc mra 60-93Vo. Reactionswith 6 equir" of Sml; fo
in 50-tl{X? rrld the 4-phenylbenzamides, Review of SmI2 reduction of luliJct r reviewsvariousproposedmechanismsftx thc may involve organosamarium(lll)intcrrr'$
lE.J. EnholmandS. Jiang,Tetrahednn Ictut 2 Y. KamochiandT. Kudo,Tetrahednn4 lJ 3J. Inanaga, o. Ujikawa,andM' YamagrrtrrIa aD.P. CurranandR.L. Wolin,S.rn/erl. -:l- r19 s J. Collin,J.-L.Namy,F. Dallmer.and l{ B li 6T. Imamoto,T. Hatajima,N. Takilama'T Tt Perkin I, 3127 (1991) 7 S.M. Bennettand D. Larouche. S}n/r'r' {f I 8 J. lnanaga, Y. Handa'and \l l. Y. Yokoyama' e G.A. MolanderandJ.A. McKie.J ()rs 5: r0A. S. KendeandJ.S. Mendoza,Tetrahedna l' ll D. P. Curran,T. L. Fevig,C. P. Jaspcrscrn: \
Samarium(Il) iodide-Lithium emilc. Stl Reduction of esters, anhydrides. u col by SmI2 in combinationwith a ba*- (Lr\H; : source)in THF at 25' to alcohols
Samarium(Il)iodide-Lithiumamide
Sml2
,^-t.-.-^1
( ,) ,
|
rHvoueu
!g
CHS
l- ?".
I
g"
CH,
_l
cH.
3lt
r'"* lc]1-o'l tuYo fi^;o \'t-l I Y---/ | L
a
2
2%
l.rr,o1"rr1.cro
8o/o
+ r- :,, large-sizedrings can be obu::h Sml2 in THF followed by :r.l,,.rlkanones.
9H,
,l--L-r
( l F o v-t-/ t
)
tj|F-t.ri3osiR3
OAc
/AYlr
+ (
9H'
| F o \--1-< cH. \__16HrgOSiRs
I
{ u n 2 1 n1
(60%)
(5-20o/o)
coocHs 2 ( 1: 1 )
T:J.irmentof unsaturated ketones n.: r)-memberedcarbocycles.The ll: r .rriouselectrophilesto provide rtL \\clcctive.
qQ
zcH,
l'' A-cH" T
_
>150:1)
) ..:n cffect cyclization of the ' ': HMPA) to give a bicyclic f(i.:l()n.
Reduction of RNo2.t(. primary, secondary,or tertiary nitroalkanescan be reduced by sml2 with cHroH as the proton source to either alkyr hydroxylamines or amines dependingon the amount of Smr2. Reactionswith 4 equiv. of Smr2 at 25" in THF/cH:oH (2:l) for less than five minutes provides hydroxylamines in yields of 60-93%. Reactionswith 6 equiv. of Sml2 for eight hours provides amines, identifiedas the 4-phenylbenzamides, in 5o-80o/o yield. Review of sml2 reduction of halides and radicals. This report (69 references) reviewsvariousproposedmechanismsfor thesereactions,and suggeststhat both reactions may involve organosamarium(IlI)intermediates.rr I E.J. Enholmand S. Jiang, Tetrahedron Leuers,33, 6069(lgg2). 'Y. Kamochiand T. Kudo,Tetrahedron, 49, 43Ol(1992\. 3J. Inanaga,O. Ujikawa, and M. yamaguchi, Tetrahedron Letters,32, 1737(l9gl). a D. P. Curranand R.L. Wolin,Synleu,317 (1991). 5J. Collin,J.-L.Namy, F. Dallmer. andH.B. Kagan,J.Org., 56,3ll8 (1991). 6T' Imamoto'T. Hatajima, y. Kamiya,and r. yoshizawa, N. Takiyama, T. Takeyama, J.c'.S. PerkinI, 3127 ('19911. 7S.M. Bennettand D. Larouch e, Synlett,U05( 199| ). "J' fnanaga, Y. Yokoyama, Y. Handa,and M. yamaguchi, Tetrahedron Letters,32,637r(1991). " G.A. Molander andJ.A. McKie,J. Org., 57, 3132(lgg2). r0A. S. Kendeand J.S. Mendoza,Tetrahedron Leuers,12, 1699(1991). rr D. P. Curran,T. L. Fevig, p. C. Jasperse, and M. J. Totleben, Synteu,943(1992). Samarium(Il) iodide-Lithium amide, SmI2_LiNH2. Reduction ofesterc, anhydrides, or carbonyl groups, These groups can be reduced by SmI2 in combinarionwirh a base(LiNHr, LiOCHj, or KOH) and methanol(hydrogen source) in THF at 25" to alcohols.r
3r2
Selenium dioxide
Sml2,LiNH2' C H g O HT, H F ,
c6HscoocH3
Cyclic diacetylenescan also be obtatt as s-cyclodecynone7. In this caseonlr
C6H5CH20H
64o/" F
C6H5CH2NH2 8"/o
CoHsCHzOH 81"/"
C6H5CONH2
C6H5CH2NH2 + 45o/"
C6H5CH=NOH
c6HscH20H 3/o
wo
80+
7
t - \ \-r---/
Letters'32' 3511(1991)' rY. KamochiandT. Kudo,Tetrahedron Selenium dioxide' SeOz' of a to cyclic diacetylenes involves reaction Cyclic diaceEtenes' A useful routc c y c l i c d i k e t o n e s u c h a S l w i t h s c m i c a r b a z i d e a c e t a t e i n e t h a n o l t oaffords a f f o r dcyclic 2.Reaction (3 and 4)' which on thermolysis of 2 with SeO2 tbrms selenadiazoles diacetylcnes5 and 6'
c- 2q
*o*-5" 9
I R. Gleiter,D. Kratz,W. Schafcr'ir: \
H2NCONHNH2'HOAc c2H50H 94o/o
H2NOCHN
Selenium dioxide-Trimethl lsilll I Aromatimtion of cYclohcxctct t fected in refluxing CCl.r br trcatnral 11,427; 12,543). Note that a crckrttt
2
gi#=
__1t"il
\'{]!X*
*'iu-J.-,^--(,i\ ;,
?"'
..,S"*--r--/-\-rl
.)
Y
CHCHd z
3
-'*"
I "*'"'''""0'
I
rJ.G. l-ee and K.C. Kim. Tetrahe'lnqL
I
5 (4olo)
6 (27%)
Silver trifluoroacetate, CF.COO"\ga-Allqlation of ketoncs" Srlr (but not bromides)activatedbr stlra generallymoderate.this reaclion ts I
Silver trifl uoroacetate
313
Cyclic diacetylenescan alsobe obtainedby a similar strategyfrom a cyclic ynone such as s-cvclodecvnone7. In this caseonlv one selenadiazoleintermediate(9) was formed.r
20t
:o*
----
C6H5CH2NH2 B% \
i:NN: I
C6H5CH20H 3o/"
.1--,
2
1 Bovo
o 7
\
SeO2
',li'-NHcoNH2 a
, , rI )
\-?v l;i.
,.ct\'lenesinvolvesreactionof a rn cthanol to afford 2. Reaction . r ()n thermolysis affords cYclic
Cu,200'
*or-5" 9
1R. Gleiter,D. Kratz,W. Schiifer, Soc.,113,9258(1991). andV. Schehlmann,Am.
H2NOCHN
Selenium dioxide-Tbimethylsilyl polyphosphate (PPSE). Aromatizption of cyclohexenes and clclohexadienes.t This reaction can be effected in refluxing CCla by treatmentwith SeOz (1 eq.) and PPSE (10 cquiv.; 10,437; 11,427; 12,543).Note that a cyclohexanefused to an aromatic ring is not affected.
2 CHe
I '
-
Y
'"3a,::" ?r. ,i.\ -l*"\2
cHcH3)2
I
cHCH3)2
-* J2.Cu(o) ' 80'
I J. G. lre and K. C. Kim, Tetrahedron Letters,33, 6363(1992).
t
6 (27o/o)
Silver trifluoroacetate, CF3COOAg. 14,331; 16,30l -302. a-AllElation of ketones.l Silyl enol ethers can be alkylated by n-alkyl iodides (but not bromides)activatedby silver trifluoroacetate(1 equiv.). Although the yields are generally moderate,this reaction is a useful route to a-alkyl ketones.
314
Sodium borchydride-Cerium(III)
chloride (Luche reagent)
OSI(CH3)3
cF3cooAs cHeclz ,
+ RGH2[
Sodium bor*rl
cH2R
Ff(
a
qr-Apz
83Yo 56Vo 50/"
R=H R = CHsCHz R = CzHsOeC
_o [-K.-cns \l-(\cHe \ o
R"/
l a , R l , R 2= C H g
NaBH4,CfuOH, -78" rc.w.
Jefford, A.w.
Letters,33' 1855 Sledeski,P. Lelandais,and J. Boukouvalas,Tetrahedron
CH3OH NaBHa , -78' , CeCl2,
(1ee2).
Silver trifluoromethanesulfonate' AgOTf' (3 equiv') markedly promotes Iod.ocyclization of carbamates'l Silver triflate iodocyclizationwithlr4/,s-Stereoselectivityofcarbamates(1)derivedfromaminoacids,
o 1 2 c, c l 4
cooczHs -+#-
\o
"*\- |
,lcooc2Hs
f"''
t3 r) \-J
(20:1)
including NaBHa, results in highlr r-il N\-^
(cH3)2NcHl"^
"5"rr,
4 rR.J. Heffner,J. Jiang,andM.M.
Joulli6,Am.Soc.,ll4, 10181(1992).
N-Sulfinyloxazolidinones, chiral. Two of these reagents,I and 2, have bcen studied. One is derived from (4R,5S! norephedrine(HXp), the other (2) is derived from (4S)-phenylalanine(HXo).
o
o
l l l czHrzS'.rAo
\'J
cnlcuHs (R)-1
o
o
i r i i crHru"S'-"Ao
L/-
Bzt-" (s)-2
318
(*)-Sparteine
Asymmetricsynthesisof sulfoxides,sulrtnatus,and sulfonamides. Thesesulfinywith inversionat sulfur.l reactwith a wide rangeof nucleophiles latingreagents
s - B u L i .1 . O(CzHr)r. -78,'-
(l) \ru/ I
Boc 2
(S)-2 + CH3MgBr
THF, .78" 90%
NaOH
o
Hs\^,2',uc(cuHs)z rr ',H
e C7H77"-CH3
3, 99.3%ee
or l
zn
Ed
czHrzs-"r2cooc(cH3)3 > 987oee
Tt{tr
(S)-2 + (C2H5)2NMgBr
Enantioselective deprotonation of catt carbamatesof a sterically demandingorazolrri deprotonationwith sec-Buli/(-)-sparteine Tl t: sequentialreaction with CHTSOTH/Ba(OH
ot l
-7Ro
91o/o
9G
Ao" o
99%ee
(s)-2 + BTCH2COOC 'nils (C"'
r-8
a c7H77"-N1c2H5;2
1) s-ButJI 2) cH3l -
RO---^.--OR
> 98o/o€€
&3\ CHe l -
9H.-Jl
R= ('-n.-N _ O /
/
,
i
\
O Cri.
'Ctt.
I D. A. Evans,M. M. Faul, L. Colombo, J. J Bisaha,J. Clardy, and D. Cherry, Am. Soc., ll4,5977
(tee2).
RO--.( )z-.OR
(-)-Sparteine,
1) s-BuLr t O 2) s-AuU t O
( )-1
Asymmetric deprotonationr Treatmentof Boc-pyrrolidine(2) with a slight excess of a mixture of (-)-1 and.sec-Bul-i(1:1) in etherat -78" for severalhoursprovidesa chiral 2-lithio-Boc-pyrrolidine(a), which reacts with various electrophilesto provide 2-substitutedBoc-pyrrolidines in 88-96% ee. A typical synthesis is illustrated in equation(I).
f S . T . K e r r i c k a n d P . B e a k ,A m . i r r c . . l l 3 . e - r r \ | 2M. Paetow, H. Ahrens, and D. Hoppe. Tetralvdm
(-)-Sparteine
?\. dnd sufunamides. These sulfinYp : . . \ \ i t h i n v e r s i o na t s u l f u r . l
/
(l) \ru/
\
a
s - B u l i ,1 , -78o. O(CzHs)e,
I
Boc 2
(r)
1
i . J
a
""6t"utu"
NaOH,
%b#L
(*2.,,,616usu,, H
O
H
3,99.3%ee
te:
o q
6 -.r-/"-CH2cOoC(CH3)3 > 98o/o€€
-i-t-7
-eu{-
Ao" oH
^f.l^ v i
319
Enantioselective d.eprotonation of carbamates.2 1,3- or l,4-Diols protected as carbamatesof a stericallydemandingoxazolidinegroup undergohighly enantioselective deprotonationwith sec-Buli/(-)-sparteine. The protecting group can be removed by sequentialreaction with CH:SOrH/Ba(OH)2.
--
N (CzHs)2 '98%ee
RO.._-.--.---OR
1 ) s - B u L i , 1 RO_.._.,-Y-OR 2) cH3l 83"/" CHs
CH. t -
9H.-]-t
q = (-..,'_-N_ ,O
/ ) t O c4'CH3
HO-.....^-.*..O
H
I
CHs >97o/oaQ
RO..-.( )2,,-,OR
1:CHgt Ro_.r.( 1) s_BuLi, )z,r.oR 2) s-BuLi'1;cH3l > T T CH3 CH3
I
I
HO _ Oz-u.OH
l
f lt '.-pvrrolidine (2) with a slight excess il' ,r -78' for severalhours provides a r. .( rrh various electrophilesto provide : \ tvpical synthesis is illustrated in
l
CH3 CH3 (S,S/R,S)= 98:2
rS.T. KerrickandP. Beak,Am.Soc.,1f3,9708(1991). I M. Paetow,H. Ahrens,andD. Hoppe,Tetrahedron (1992). Letters,33,5323,5327
N-sulfonyloxaziridines
N-sulfonyloxaziridines. Asymmetric hydroxylation of enolntes'
Davis and Chenr have reviewed this
reactionusinginparticular(R,R)-and(S,S)-2-phenylsulfonyl)-3-phenyloxaziridene(1) (2)' Of thesereagents'I and (+)- and (-)-2' derived and (camphorylsulfonyl)oxaziridine from(1R).10-camphorsulfonicacid,providehighestenantiose|ectivityandinadditionare easytoprepare.l.heyareeffectiveforhydroxylatationofketones,esters,B-ketoesters, amides, lactones,and lactams.
6H.{ O .A.nCoHs
c6H5s9r/N-" (R,R)-1
^_-N-7"
.nCoHs
c6H5so" V (s's)-l
0Hs \>/\ /
4-\>y \s7v
Thntalum(V) chloride/Zinc. 15. -r Reaction of Th-allcyne co;21 fuom TaClsf Zn with unsYmmc'trica regioisomericallylic alcohols * rth
(both steric and electroniceffeost r group. The complexes from acr'tr
at the position a to the esler ertxt mainly at the position B to thc an
OrO (+)-2 rF.A. Davis and B.-C. Chen, Chem' Rev', 92' 919 (1992)'
=CCOzCzlt C1eH21C
c-C6H11C=CCON(CN
I Y. Kataoka,J. Miyai, M. Tezula. l'
R,R-Tartaric acid, 16, 3ll-ili Asymmetric allY ltitanatioa d from the chiral diol R,R-l derircd of aldehydesin )9OVo ee.
::.i C'henl have reviewed this (1) l.,i:,'nvl)-3-phenyloxaziridene n:. I .rnd(+)- and (-)-2' derived rr:: ,'\clcctivityand in additionare 1 : \ctones, esters,B-keto esters'
6H.{ C.H.
,CHg
/ \>--.' \ /
4\* \s{
Tantalum(V) chloride/Zinc, L6, 312. The Ta complexes formed Reaction of Th-allcyne complexes v,ith RlFPC:O.I compoundsto form two with carbonyl fromTaCl5fZn with unsymmetricalalkynesreact substituents on the alkyne on the regioisomericallylic alcohols with a ratio depending in the carbonyl of the substituents (both steric and electroniceffects)as well as the size mainly compounds with carbonyl group. The complexes from acetylenic esters react react acetylenic amides from at the position a to the ester group, whcreas complcxes mainly at the position B to the amide.
OrO (+)-2
1) TaCls/Zn
CloHgr
2)PrcHo' C1eH21C=CCOeCzHs 760/o
H
fOzC2Hs
lPr HO (95:5)
1) TaCls/Zn
"i#* c-C6H1 1C=CCON(CH3)2
c-coH1r /coN(cH3)2 H Pr-1 OH (90:10)
I Y. Kataoka, J. Miyai, M. Tezuka, K. Takai, and K. Utimoto,J. Org', 57,6796 (1992)
R,R-Thrtaric acid, 16, 312-315. Asymmetric allyltitanation of RCHO.I A complex, (R,R)-3, prepared in two steps from the chiral diol R,R-L derivedfrom l-tartaric acid(14,232;16,314),effectsallylation of aldehydesin )90% ee.
o o a
322
R,R-Thrtaric acid
CoHsrOHHOr rC6Hs C.Hut\-'"\C^ 9E:9!9I41 (R,R)-3 -tt * cpr,"r, NI94dr 1n,ny-z / \
oxo
cilt
'cH'
Acyloxyborane catalyzed allylatioa.' t c by reactionof borane' THF with (2R.-1RF'.( the reactionof allylsilaneswith aldehvdest< ee. The geometry of the silane has no cilcr l-PrO
(R,R)-1
Zr>/t t
1) (R,R)-3
c.HscHo
O
r
l
COOH
|
O.'\-,.COOH
i
l
BH:-X
:
ot
\Ao-,-p,
oH
-74: 2) NH4F'
i
(2R,3R)
"urrL"r, ( S ) , 9 5 %e e
-OH
OH
c6H5ycHo (*,*)-r, c.rr--TA.,scH" * cuHrQf^.r, w'12 dH. 6r? Ar? 48o/o,9oo/"de
487o,98.8"/"de
fcr a new asymmetric Asymmetric synthesis of B-lactams'2 The key reagent acid. Reaction (2S,3S)-tartaric from synthesisof B-lactamsis the chiral imine 1, prepared of which configuration the 3' of I with an ester enolate (2) provides a B-lactam
NAn
"ofo"t. "
An=c6H4ocH3-p
JL >(,o-l-oct. |
t-t-
Ho)'',,,,.oCHs
cH;\o) ",,.ocH"
CHs | - C " H . C H O +' ^ , , CH1.2',.,,.Sr(C}rr) E / Z= 5 1 3 9 I A. Hafner. R. O. Duthaler, R. Manr. (i
Rrir
rr4,232r (19e2).
2T. Fu.lisawa, Y. Ukaji,T. Noro.K. Datc r:: I I K. Furuta,M. Mouri, and H. Yamanxr.,-\.lir
a, u, at , at-Tetraaryl-1p-dioxoh*{- l i l
OH 5
o (\\''.
\ff HO
CH30.--,'r
(CH3)3Sn^
o
c
t
cur,utV
(CHd4C-CH 6
OH 7
o
ll o, C^H^"n'd 1co l i l 2 + (CHs)sSiC'=CHG;-
rot\'
si(cH3)3 I
7' The reactionof 2 with to obtain an annelatedphenol This reactioncan also be used rhodacycle' provides the phenol 8 via a I under a CO atmosphere (1992)' 1A. Padwaand S'L' Xu,Am Soc''ll4' 5881
Addition of (ArS)2 and (ArSct: b I catalystfor addition of diaryl disulfrlcr (Z\-1,2-adducts in high yield lequanxr I
Tetrakis(triphenylphosphine)palladium
--:'.:rncthvlgroup.Thus the siloxanering )l .-r\ lation of an adjacentdouble bond. t . ':
rl). ), t r'.,r,propcne (2) forms a rhodium vinyl c .1, i,r form an oxepine 4 and a phenol ,"-- I 5 in practically quantitativeyield.
JZ7
Tetrafluorosilane. selective cleavage of silyl ethers.t This gaseousreagentcan cleave silyl ethers in cHzcl2 or cH3cN at 25' in rates that are strongly dependenton the substituents at Si. The relative ratesare in the order: Et3si > r-BuMe2Si > r-Bu(c6H5)2si. Silyl ethersof phenols are stable to SiFa in cHzcl2 at 23" for 24 hours. SiFa is an excellent reagent fbr selectivecleavageof primary or secondarysilyl ethersin the presenceof tertiary ones. 1E.J. Corey and K. Y. Yi, Tetrahedron (IggZ\. Letters, 33, ZZgg
Tetrakis(triphenylphosphine)palladium.
{ - C= C H ( 3 )
Pr * 5 (Bolo)
€2'.
CH2Pr 4
coupling of 2-bromonaphthoquinones with stannanes.r The 2-bromonaphthoquinone I undergoesStille coupling with tetraalkyl-, alkenyl-, and aryltrialkylstannanes in good yield under catalysiswith pd[p(c6Hs):]+ or cr2pd(1,1/-bisdiphenylphosphino)ferrocene[Pdclr(dppf)]. Addition of cuBr usually improves the rate and/or yield. Thus coupling of l with the stannane2 provides 3 tng2To yield. This product was converted into the antibiotic WS 5995C (4) in 2 steps.
too.z"Jn-, +0.
(Y,, cH2Pr
curri a
I
\
?'
o
z-")"'..8'
w + HO
o
CHsOt -1r-CHs i l t (CH.I^Sn/'{
I coNHc(cH3)3
Pd(o),CuBr 82/o
2
OH 7
Y,,
1) t-BuOOH 2) HC|O4
-
98o/"
si(cH3)3 8
r.:.l.rtcd phenol7. The reactionof 2 with t ,r.r a rhodacycle.
):
Addition of (Ars)2 and (Arse)2 to l-ailcynes.2 pd[p(c6Hs)3]4 is rhe mosr effective catalystfor addition of diaryl disulfidesand diselenidesto terminal alkynes to provide (z)-L'2-adductsin high yield (equationI). Note that phoroinitiated addition of (c6HsSe)2
Tetrakis(triphenylphosphine)paltadium
(l) CH3(CH2).-C=CH
+ (C6H5Y)2
Pd(o), 80'
CH.(CHO)" H t'' /
/:'. c6HsY
YC6H5
Y=S
91V"
Z, 1000/o
Y=Se
82/"
Z, 1000/"
HzN../rCH
oTf l
r
(cH3)3c'\cH2
HO" I
(ll) R-C=CH + (C6H5Se)2
R.
\
hv
o ao^ (cH3)3c ..nA ) .,,.",."u, *
/,SeC6H5
C6H5Se'
H
btt, H
(E),95 : 5 to 1-alkynesresultsmainly in the (E)-1,2-adducts (E/Z:95:5), equation(II). Carbonylativeadditionof diaryl disulfidesand diselenidescan alsobe effectedwith the Pd(0) catalystto form (Z)-1,3-bis(arylthio)-2-alkene-1-ones and (Z)-1,3-bis(arylseleno)2-alkene-1-ones,respectively(equationIII).
(lll)CH3(CH2)u-C=CH+(C6HsY)2
co, pd(o) CH3(CHds \>/1,.ycuHu 60" | tl
c6H5Y
O
Y = S
860/o
z, 1000/o
Y = Se
8oo/o
Z, looo/o
r"\r'
l l
r"OTf
|
|
+ 1 . c !
Somewhatmore efficient catalr*r r Cyclization of triynes to Dr,n:crr, alkyne 2 both cyclize to the hcnzcrx r (3 mol %) and a base or acid rn rcflu
Coupling of acid chlorides with (E)-BqSnCH:CHSnBuj; 1,4-diketones.3 The Pd-catalyzedStille coupling can be extendcdto coupling of acid chloridcswith (E)-1,2bis(tributylstannyl)ethene. Uncxpectedly,a 1,4-dioneis formed,evidently by reductionof an intermediateenediketoneby BurSnCl. Reactionof an a, p-unsaturatedacid chloride also leads to a 1,4-diketone,as does the reaction of an acid chloride with a B-stannyl enone.
\
SnBu3
(cH3)2c=cHcoct '
o
H 1, E = COOCzHs
#
"u"ul*.ur, o
z
A-,q
Or
?r. ? a6; ora-\-\z^-",1coHs
ll
CH.
6
o
Bu3Sn, C6H5COCI+
eto D.
o
2
CH=CHSnBu3
Chiral oxazolines; Stille carbonylative coupling.a Pd-catalyzedcarbonylative coupling of triflatesof ketonesand phenolswith chiral amino alcoholsprovides B-hydroxy amides,which cyclize to chiral oxazolineswhen treatedwith thionyl chloride.
A partially intermolecularverivrn rs 1 4 and 3-hexyne cyclize to 5 under rhc se However, cocyclization of (E)-p-hrrrm derivative 7 (equationII).
Tetmkis(triphenylphosphine)palladium
CHe(CHe)c H
t'* /
a:
YC6H5 c6H5Y z, 1000/o
H2Ny,CH(CH3)z
OTf
+ (cH3)3c-\
cHr*
Pd(o),Licl THF.55. > B3o/"
co
Ho)
z, 1000/" R .Qo t v v
o
ao,
l( (cHd3c ^J,,'"rr"rd, #tcH')fi1,,.r,.r,,, Y H 6u"
D eC6H5
H
E, 95:5 , / - 95:5), equation(II). lc:rJcscanalsobe effectedwith the I -"lcs and (Z)-1,3-bis(arylselcno)-
CHr(CHz)s ,,\Z>1YC6H1 t l l c6H5Y O z, lco%
"'cH(cHs)e
. 1+ + co=5%* co-- ^^iJ
f)--o'' \2-\2
ry-)
Somewhatmore efficient catalystsarc pd(dba)2/p(C6H.5) and pd(OAc)/dppp. cyclization of triynes to benzenes.s The triyne I and the bromoalkenylalkyncalkyne 2 both cyclize to thc benzcnedcrivativc 3 when treated with this pd complcx (3 mol Va) and a base or acid in refluxing CH3CN.
z, 1000/o =('HSnBus; 1,4-diketones.3 The lrrr of acid chlorideswith (E)-1,2Ir :,,rmcd,evidentlyby reductionof [ .::] .r, B-unsaturatedacid chloride .r:r.rcidchloridewith a B-stannyl
o
tl
o
I'd-catalyzedcarbonylativecourrrr,, alcoholsprovides B-hydroxy n,.: *ith thionyl chloride.
\
r
-
i
:rcfy 'YcH. -o
z
c H-3 tol
'
l C H " H \. l,E=cooc2H.
o tl
tu-u),_"utu
.&cuHt
'l'
Pd(o),HOAC cH3cN,
-;-\
)
il
Pd(o),N(c2H5)3 cH3cN,
,/
*.Br \\ I CHzCHs 2
A partially intermolecularverison is possible,but lessefficient.Thus thc bromoenyne 4 and 3-hexynecyclizeto 5 under the sameconditionsin 4ova isolatedyield (equationI). However, cocyclization of (E)-B-bromostyreneand the diyne 6 results in a fulvene derivative 7 (equationII).
Tetrakis(triphenylphosphine)palladium
si(cH3)3 Et (t)
ll
si(cH3)3 Pd(o)N(czHs)s e_ ;-..,74;CrH, ---
4o%-
-1AA.,ru
oANet,
Et
e
(il) :x E'
f-_4CH \^,
/CaHs
*
.CH,
ll
Pd(0).N(c2Hs)3 tr 52o/o
Br2'
6
E'
poHs
/y^:, V--\,/ 7
Coupling of aryl iodides and arylboronic acids.6 This Suzuki cross coupling can be effectedwith this Pd(0) complex as catalystand Na2COr as base.It provides a rapid accessto rn- or p-tcraryls.
o-+
grF
ffil arF
Pd(0),NaCO3,DME
(HO)28- \ /
cH3 (HO)2BC6Hs
l"
r-
.'(t,
r N . T a m a y o ,A . M . E c h a r e 2 H. Kuniyasu, A. Ogaua. !
(1ee1 ).
3 M. Per6z,A. M. Casran '. a A. I. Meyers,A. J. Rd'lr-h 5 E. Negishi,L. S. Hanrng 6C.M. Unrau,M.G. Carn Tetramethylammoniur
Reduction of a-hy/ I in HOAc/CHTCN ( | I product, whereas (E)-l Bzl I
o-N Ho l l l r-Pr,Mr(4-2
H3
HO N-O l , l l-PrY,(E)-2 This coupling can be extended to a synthesisof rn-quinquearylsby using a 1,3dihalobenzenesubstitutedat C, bv a directing metalation group: CON(C2H5)2,CN OMOM. or NH,.
Bzl I
Ho
o'N
l r l
r-pr,,,Yi-l cHs
Tetramethylammonium
si(cH3)3 '
'
tr - x/--'z\','CzHs i l | E'vcrHu
tr ->1/----,2'x tr F
/
\
| |
\:/
n
r>
\v\..1aB(oH)2
,t'(t, o
triacetoxybomhydride
331
Pd(o),DME,
\)
ttEt,
PoHs
/
\_---v 7
I'rr. Suzukicrosscouplingcan r.( ( ) ;1sbase.It provides a rapid
lN. Thmayo,A.M. Echavarren, and M.C. paredes, J. Org., 56,64gg(1991). 2 H. Kuniyasu,A. Ogawa,S.-1.Miyazaki,I. Ryu,N. Kambe,andN. Sonoda, Am. Soc.,ll3, 9796 (1eel). 3,M.Perez,A. M. Castano, andA. M. Echavarren, J. Org., 57, 5047(1gg2). a A' I' Meyers, A. J. Robichaud, and M. J. McKennon,Titrahedron Leuers,33,1rg1 (1992). z. owczarczyk, M. M. Mohamud,and M. Azy,ibitt., t3,32s3 (1ss2). ::L. vr. ).i,,r],:..t _t, lu:". unrau.M. U. Campbell,and V. Snieckus, ibid., 31,2j73 ,lgg2\. Tetramethylammonium triacetoxyborohydride (1, t4, 2gg_3OO; 16, 324). Reduction of a-hydroxy oximino ethers (2).t This reduction can be eff.ectedby I in HOAc/cHrcN (1:1), -35'. Thus reducrionof (z)-2 providesmainry the l,3-anti product, whercas (E)-2 provides mainry the r,3-syn product. Note that an additionar
Pd(0),NaCO3,DME
Bzl j
o-N
Ho
l r l
r-pr--*-p. (z)-2
100%
Ho ,*-oBzl l : ,-pr-^*i-p, anti-3
+ sYn-3
67 : 33
CHs
Ho
*-oBzl
Ho ,*-oBzl l l
t t l
r-Pr--\*i-pr (E)-2 rz-uuinquearyls by using a L,3L:r,'n Broup: CON(C2H5)2,CN
+
,-pr-^*i-p, syn-3
anti '3
91:9
Bzl I
Ho
o-N
HO "-oBzl
l r l
l-Pr-*l-Pr CHs
94o/o
t iprl^*i-pr
l
+ 1 , 3 - a n t-i3
cHg 1,3- syn-3
96
332
2,2,6,6-Tetramethylpiperidinyl-1-oxyl
chiral center at C2 can overcomethe influenceof the oxime geometry (last example). I D. R. Williams and M.H. Osterhout,Am. Soc.,ll4, 8750(1992).
Tetramethylguanidine. Michael/aldol reaction,t The key step in a synthesis of the alkaloid huperzine (3) involves a Michael/aldol reaction of the B-keto ester I with methacrolein to A provide the bridged ketol 2. The usual Michael reaction catalysts(NaOCHr, BuaNF, ZnCl) arc ineffective, but the desired reaction can be effected in 93Vo yield with tetramethylguanidineas catalyst. DBU can also catalyze this reaction. Conversion of 2 to 3 is effected by dehydration of the ketol (45vo yield), wittig reaction of the ketone
H. 1 Tetraphenyldistibene, (C6Hs)3SbSHCRCH2I - RCHzOH. Irradiation of I reactswith RCHzI to form (c6H.)rSh('H:n
irradiation of a mixture of the iodidc 2 arrJ This product is stable to O1. but is oridrz contrast, the same reaction of I rr ith 5 p
CHa .O
,
cH.{ts-^ O-\--T.-\
r
1-------------. 80-85a
o l
"r.*o aY*Yott' ?'/'2
*
?" A"ro "
CHg
HN=crN(cHg)zrz -,s%*
2 (R1CH2t)
11
coocH3
9cHs
t"t tr1
1
oxo
+
1
40-6G
CHS CHS several steps
5 (R2CH2t)
2
which is oxidized in air to the alcohol 7 Tl convertedto a stibenethat is oxidizc'dhr r
(73Voyield), Curtius rearrangementof the ester to with ethylidenetriphenylphosporane of the o-methyl ether to a pyridone (iodotrimethylsilane). cleavage group, and an amine I A. P. Kozikowski,Y. Xia, E.R. Reddy,W. Tiickmantel, I. Hanin,and X C' Tang,J' Org'' 56' (1991). 4636
(rll) ca/#t
8
2,2,6,6-Tetramethylpiperidinyl- 1-oxyl (TEM PO), l. ortdation of a-amino or a-alkory alcohols.t (ct., 14,302). This oxidation of optically active a-amino or a-alkoxy alcoholswith sodium hypochlorite(slight excess) catalyzed by TEMPO and NaBr can provide the correspondingaldehyde with no racemization.Highest yields are obtained with toluene/ethyl acetate/H2Oas solvent with 1-2 mol Vo of TEMPO and 1 equiv. of NaBr. Overoxidationto the acid can be minimized by rapid stirring. Carbamoyl groups (Boc or Cbz) are preferred for protecting groups of the amine. Yields are generally 80-9OVoand the 7a ee is >95%' I M. R. Iranna, T. J. Sowin,and H. E. Morton,Tetrahedron Letters,33, 5029(1992)'
I A. G. M. Barrettand L. M. Melche r. .{n .!e
Tin.
Allylation of -CHO (l3.let't) ' Th. moted by tin in an aqueous/organicwrlrcnl proceeds with threo-selectivit\'({-6 -i I I
333
in-.. rcometry (last examPle)' FJ
1q.1. rrl the alkaloid huPerzine ir r-icr I with methacroleinto o: ..rtalvsts(NaOCH3,BuaNF, i.( .ttccted in 93% Yield with u, :hi\ reaction. Conversion of d, \\ ittig reactionof the ketone
(l)' Tetraphenyldistibene, (C6Hs)2SbSb(CoHs)z (C6Hs)2Sb" which RCH2I - RCHzOH. Irradiation of 1 produces the radical to RCH2OH' Thus oxidized be can which reactswith RCH2I to torm (C6H5)zSbCH2R, in 80-86% yield' 3 stibene in the I results irradiation of a mixture of the iodide 2 and Thisproductisstableto02,butisoxidizedto4inhighyieldbyalkalineH2o2'ln and in low yield to give 6' contrast, the same reaction of 1 with 5 proceedsslowly
.,:\r"K: o\_1S
+
1
"r.+5
+
RlCH2Sb(C6H')2
80-86%
H2O2,-OH ---^.RlCH2OH 84"/o
3
4
CHs HN=clN(CH3)212 )HO
2 (R1cH2l)
93"/"
11
9cH. (") +
1
#:,.
hv "''
Oz
-
R2CH2Sb(C6Hs)z
40-60%
;""
lff,:ii
7
5 (R2CH2|)
3 whichisoxidizedinairtothealcoholT.TheacycliciodideSunderthescconditionsis overall yield' convcrtedto a stibenethat is oxidized by air to 9 in 59o/o tL. :Jitrrangementof the ester to ) i :\ ridonc (iodotrimethylsilane)'
1) hv
i i , - r n . a n d X . C . T a n g ,J ' O r g ' , 5 6 '
*
(lll) Cul#t
1
2) oz 59/o
8 ,.r . l;1.302). This oxidation of Nr.rnr hvpochlorite(slight excess) !.,"r\ponding aldehYdewith no cr.r -rhvl ^cetatefKzo as solvent (t,.,r,rridationto the acid can be ): ( \/) are preferredfor Protecting ni :hc 'i ee is >95Vo' i
:.'.. -13,5029(1992)'
O.
CHzOH
9
f A.G.M. BarrettandL.M. Melcher, Am' Soc',l13' 8177(1991)'
Tin. Allylationof-CHO(13,2g8)'tTheadditionofallylbromidetoaldehydespromotedbytininanaqueous/organicsolventhasbecnextendedtoaldoses.Thereaction can be converted to higher proceeds with threo-selectivity(4-6.5:1)' The products
Tin(II)
chloride-Triphenylphospine
o Sn, CzHsOH/HzO
OH OH OH
TsN.C
(((((
* "r/u''
cunr\.'ncoHs
o AcH, I
a^cH,
D - glucose
Ho-l l-oH
Snlz/P(Ph)3.25:
+
BuSnl2/ P(Ph)-i{
rot
+
Ho-]
+
6.5:1
HO-l
l-oH
loH
| FOH
l-o'
r-oH
lot I
L_OH
I I. Shibata, A I]3hL N. Yoshimura.
Tin(IV) chloride. [4 + 2] Cy cloaddition ol nita in thermal reactions with drcrr reactionswith dienesto form rr r(equationI). Nitronatesare als.
95:5). This reaction is applicableto both (E)- and (Z)-alkenes,but the former react more readily. These ene adductscan be transformedinto optically active allylic alcohols(4) by N-alkylation and in the presence conversionto an aryl allylic sulfoxide (3), which undergoesrearrangement of a thiophile (piperidine)to 4, with retentionof configurationat carbon imparted in the ene reaction.The overall processeffects enantioselectiveallylic oxidation of an alkene with retention of the original position of the double bond.
chloride
Tin0V)
GH3,..VR TFA 1) NaO6N, ? p*g;1 2) Soclz , p*6ArrS-'"
n
SnCl4, + CH,Cl2,
-78'
O... /' *ROOC-*-S--,rL.R
65 - 91%
H
1
z
eH.
2 (>95 : 5)
(c2Hso)38F4
o.\ ./. .ROOC_J>L.x-R
R*OOCNHC2H5
coHsMsBr
O.r .2'
t : C2H5 CH3
a radical coupling. Otela et a/.{ present e electron oxidation of the silyl ketenerd Coupling of the two radicals then regcrrr Rearrangment of allylic aceuk n J substituted tetrahydrofurans is based on t condensationof allylic diols with a c-art Lewis acid to a tetrahydrofuran. Of rarrrt allylic diols are available by reaction of
a-hydroxy ketones.Of particularintercsrThus the acetal 1, a mixture of four stcrcc obtainsrn tbt Even higher stereoselectivity
CoHu-S:-'=-* = CHs 3
I
4O-640/ol
Piperidine
overall I i
cH3oH
*H,
"t.-Lo,.
1
cH3,, /-cH3
9H
cHs.._Le
H3C.,,.,l$R
| )-ctxt cHs/-ci
4 (84 - 100o/"ee) Mukaiyama-Michael reactions.a This reaction involves addition of silyl ketene acetalsto enonesin the presenceof a Lewis acid to form 1,5-ketoesters(13,306-307; 15,15). Surprisingly, a B,B-disubstituted enone (1) in the presenceof various lrwis acid catalystsreactsmore rapidly with the disubstitutedsilyl keteneacetal2a than with the unhinderedsilyl keteneacetal 2b, to form the hinderedadduct 3 with two adjacent quaternarycarbon atoms.Similar resultsobtain with BuzSn(OTf)2and TiCla. The result is hardly consistentwith a nucleophilic reaction,but suggeststhat the reactioninvolves
? ? " cuHuMcH. 1
+ (CH3)2C:{
/OS|(C2H5)3 OC2H5
2a
SnCl4
"i4! j' 93/o
* CHzl
/OSi(C2Hs)3
oc2Hs 2b
? cH.FH'? "urul#oc2Hs cH3 cH3 3
a,
| )-cHs CHs'/-Ci
3 for synthesis of (*)-muscarinc t6t fi (equationI).
CHzs \
(,)
cHt+oH I
* c6H5co2cH
cH3l'-oH (s)-5
o 1)SnCl4 oH3NO2CH3 2) KOH _ 35o/o
cHd
ta
cH?oH
Tin(IV) chloride
o...,2'
€ - *ROOC-*)S.,.-.,1-P b H e H . 2 (>95 : 5)
R*OOCNHC2H5 F. \r:Br
o- ,r'
onea radical coupling. oten et c/.a presentevidencethat the reactionis initiated by a enone' to the transfer by electron followed electron oxidation of the silyl ketene acetal Coupling of the two radicals then regeneratesthe lrwis acid for further coupling. Rearrangment of allytic acetals to 3-acyltetrahydrofurans's A new synthesis of by substituted tetrahydrofurans is based on the fact that the acetals (or ketals) formed a with treatment on fearfange compound carbonyl a condensationof allylic diols with The efficient' most is the SnCla acids, lrwis various Of Lewis acid to a tetrahydrofuran. with allylic diols are availableby reaction of a vinyllithium or vinyl Grignard reagent stereoselectivity' high shows synthesis new this particular interest, a-hydroxy ketones.of Iearrangesto the all-cis-3-acylfuran2' Thus the acetal1, a mixture of four stereoisomers' of 3 to 4. The reactionwas used rearrangement in the obtains Even higher stereoselectivity
c6H5is\a-\,'R : CHs
3
CHs
o
CHs
o
SnCla, c{2cl2, -23"
)-CH" 4O - 64"/o overall
Piperidine cH3oH
cHs{_e
f cH*rcnsf
CoHs
| )-ctHu cH3''^O
4 (84 - 100%ee)
- CHal ,oSi(c2H5)3 oCzHs zo
CHs
77o/o
Cft-!'-CH3
H,C'\^n
Ir:.:e rcd adduct 3 with two adjacent r lt:r Sn(OTf)2 and TiCla. The result r! .uggcststhat the reactioninvolves
CH"
1
QH
n: rnrolvesadditionof silyl ketene r :'rnr 1.5-ketoesters(f3'306-307; Ir :i: the presenceof various Lewis u:r.t silvl keteneacetal2a than with
4
3 for synthesisof ( + )-muscarine(6) from (equationl).
(S)-5, available
from
ethyl
3
(*)-lactate
aHr\ fl)
cHtj-oH
t
* c6H5co2cH2cHo
"
cH3l'-oH (s)-5
o 1) SnCla C H 3 N O 2C H 3 2) KOH 35o/"
several steps
cH20H
Hq,. '/-\ / \ c H2N+(c H3)3-ors c H./\ g
cuHr-^ffoc2H5 cH3 cH3
339
(+)-6 (90% ee)
Tin(lV)chloride-Silverperchlorate
340
1S.8. Denmark, B.S. Kesler, and Y.-C. Moon, J. Org., 57,4912 (1992). 2M.A. walker and C.H. Heathcock,J. Org., 56, 5147 (1991). 3 J. K. Whitesell, J. F. Carpenter,H. K. Yaser,and T. Machajewski,Am. Soc., 112,7653 (1990). aT. Sato, Y. Wakahara,J. Otera, H. Nozaki, and S. Fukuzumi,Am. Soc.,1f3' 4028 (1991). 5 M . H . H o p k i n s ,L . E . O v e r m a n ,a n d G . M . R i s h t o n ,A m . S o c , 1 1 3 , 5 3 5 4 ( 1 9 9 1 ) ; L . E O v e r m a n and G. M. Rishton, Org. Syn., 71, 63 (1'993)'
Tinfl9
acid.
chloride-Tiifluonoacetic
Intramolecular 15,156; 16,190-101)
Tin(II) trifluoromethanesulfoortc- ! Addition of l-allqnes ro cafu this addition, but their strong basr- ; substrates.1-Alkynes can add dirctth Sn(OTf)2 and a base(1:1). In rcacrhrr but 1,8-bis(dimethylamino)naphtha Silvlationof l-alkvneswith R,Sr(l c
ene reactions.t
use of Lewis
Fech,
acid catalysts (particularly
has greatly extended the usefulness of intramolecular ene cy-
clization. Thus a new diastereoselective route to corynanthe-type alkaloids involves (2), a precursof to methyl the ene cyclization of I to tans-indolof2,3-a]-quinolizidine corynantheate (3) by demethoxycarbonylation.
+
Ar-C=CH
RCHO
Sncla (1 equiv.) is the only common
Lewis acid that is useful for this particular ene cyclization, and even so, it also requires the presence of trifluoroacetic acid (1.5 equiv.).
2 -A mino-2 -deoxy -B -o-glucqn tetra-O-acetyl-2-deoxy-( 2.!.1-tnt*rkrr actswith alkyl trimethylsilvl c'thcrstrr >90Va yield. This procedurcis al..' r1
1 ) T F A ,C H 2 C | 2 , 2 0 o 2) SnCl4,20o 42o/o
H
(cHJ3so
CHsOzC
aOAc
oi?;S{.-oo.
2, R = COzCHs 3,R=H
NHTroc f L.F. TietzeandJ. Wichmann, Angew.Chem.Int. Ed.,3l, 1079(1992)-
1
Tin(IV) chloride-Silver perchlorate. a-Glycosylation.t This combinationproducesa speciessuchas Sncli CIO; , which is an effective catalyst for reaction of a protccted l-O-acetylglucosewith a silyl ether
TinOI) trifl uoromethanesulfour-( Asymmetric aldol reaaioa d d. as promoter of aldol condcnsatr.n o in 1973 (6,590-591), has :*'cn rrd
to form a-glycosides.
BzlO
BzlO SnCl3+ClOa
OAc + OBzl = a:1) (cr/p
ROSi(CHs)s-
I M. Yamaguchi, A. Hayashr. an.JT Vc 2T. Mukaiyamaand K. Matsuharr. ( .n
OR 86 - 95% OBzl (a/9= 90-95:10-5)
I T. Mukaivama. T. Takashima,M. Katsurada,and H. Aizawa, Chem.Letters,533 (1991)'
the Lewis acid is required arxi thr aldehydesor chiral silyl enol c'tlrn a weak kwis acid, neither cffcctrrc in catalytic (5-10 mol %) amtxrnt-r coordinatedwith a chiral diaminc .-en (f3,302) and Michael reactions( l-(-ll aldol condensation.Eventuallr tlr ,
Tin(Iltrifluommethanesulfonate-Chiraldiamine
. :.:l (1992). ,< n 'rr. ..{m.Soc.,112,7653 (1990). n - 1 n r . S o c .1, 1 3 , 4 0 2 8 ( 1 9 9 1 ) . l l - 1 . 5 3 5 4 ( 1 9 9 1 ) ;L . E . O v e r m a n ;"
341
Tin(II) trifluoromethanesulfonate, Sn(OTf )r. Addition of l-allqnes to carbonyls.t Alkali metal acetylides are usually used for this addition, but their strong basic propertiescan cause problems with base-sensitive substrates.l-Alkynes can add directly if the reactionis carried out in combinationwith Sn(OTf)2 and a base(1:1). In reactionswith aromaticalkynes,DBU is the preferredbase, but 1,8-bis(dimethylamino)naphthalne is preferred for reactionswith aliphatic alkynes. Silylation of 1-alkyneswith RrSiCl can also be promoted by Sn(OTf)2 and an amine.
iirJ catalysts(particularly FeCl3, fulrc:s tlf intramolecularene cyr':' r.rnthe-typealkaloidsinvolves lr,':.jrnc(2), a precursorto methyl
+ RcHo
Ar-c=cH
DBU, Sn(OTfl2, cHzclz . 66 - 87o/o
l. I cquiv.) is the onlY common tr:r. t. ilnd even so. it also requires
CHr N H
ll-
g
Ar'
2-Amino-2-deoxy-B-o-glucopyranosides.2 In the presence of Sn(OTf)2, 1,3,4,6(l) retetra-O-acetyl-2-deoxy-(2,2,2-trichloroethoxycarbonylamino)-B-o-glucopyranose 2 in actswith alkyl trimethylsilyl ethersto form the correspondingB-o-glucopyranosides >90Vo yield. This procedureis also applicableto preparationof B-o-galactopyranosides.
H
H CHsOzC
R
(cH3)3sio .-oAc
2, R = COzCHs 3,R=H -.)(
T z,zAon
oi?o*Voo" NHTroc
Sn(OTf)2
. -\(--,
cH2ct2,2oo
aOAc ^i?&Vo-r-\
97o/"
NHrroc (, 2
1992). rM. Yamaguchi, A. Hayashi, andT. Minami,J. Org.,56,4091(1991). 2T. Mukaiyamaand K. Matsubara, Chem.Letters,1755(1992).
| .r.!ics suchas SncliClOa , which -{ )'.rectylglucosc with a silyl ether
e'
(98o/" €e)
(s)-1 CH3--.",.CHO
I
+
3
Sn(OT02 860/o
OH I
CHs\*.\..cOSczHs
l "
osiR3
OSiMe2t-Bu
(s)-2
(S,S)-sYn-4(96:4)
Thechiralaldehyde,(R)-2,reactswithl-ethylthio-l.trimethylsilyloxyethene(3)to aldehyde,(S)-2' undergoes give anti-4with excellentselectivity(94:6).The enantiomeric thesamereactiontoprovidesyn.4.|nbothreactionsthenew|yformedchiralcenterhas the(S)-configuration,anindicationthatthestereochemistryiscontrol|edbythechiral Indeed' the same two reactionswhen amine, and not by the chirality of the aldehyde' in which the new chiral center has catalyzedby (R)-1 and Sn(OTf12provide aldols the(R)-configuration.-I.husbya,suitablecombinationofachiralaldehydeandachiral
with the r'i rr.rctionsof aldehydes is diacetate I i:' thrscasedibutyltin promotor' '.r:.,1\\t.With this chiral This high i. :,,rmcd in >987o ee' , l . t : h r d c sa n d a . B - e n a l s r \ r of the three comPonentsslnce n3'ncnts is. The amine-coordinated or l.rr:rdc. and the tin(lV) fluoride ,nrr.tric aldol reaction of aldehydes as (S)-1' rn.: .r chiral diamine such to extended been 116.::l-222), has s^rJcs.
CH3.\-,.CHO
+
3
(R)-1 Sn(OT02 85"/"
6sin.
t osiR3 (s)-2
6sin. (96:a) (R,R)-sYn-a
(R)-2
CH3\\.,CHO
9H cH..\h/cosc2Hs
+
3
(R)-1 Sn(OT02, 85%
QH CHg\9.AyCOSC2H5
I osiR3 (R,S)-sYn- (94:6)
344
Titanium(IV)
chloride
catalyst,the four possible diastereomerscan be obtained. propargylic alcohols.3 The highly enantioselective aldol reaction of Mukaiyama can also be used to obtain optically active propargylicalcoholsby reactionof acetylenic aldehydeswith a silyl enol ether. The most effective chiral catalyst is obtained by a combinationof tin(Il) triflate with a diamine derived from (S)-proline, (S)-1-methyl-2an acetylenicaldehyde lN-naphthylamino)methyl]pyrrolidine(1). Thus the reaction of
9l l o
a
o
1rr(:.c
il
2\c/+d
ru-\.--.CHa Bzl 1
1 ) H 2 O 2O , H 2) cH2N2
93"6
Q-...il
This techniquecan also cffcrr hr3 in this case i-PrOTiCl, is \uttrr: (equationI).
CHs
?
R--------cHo
+ Ets
-
?si(cH3)3Sn(OT02,1
Bzl
CHs
7o) provides the trimethylsilyl
/
\-,.
73-82/" (synlanti-95:5)
with (Z)-1-ethylthio-1-trimethylsiloxypropene
cooct
o
ll tl (f) o'-t\\ \-1 / l
in the prescnce of sn(oTf)2
Reaction of RNt r'ilh Lctanr reaction of alkyl azides *.ith .rclr reaction can also occur but can hc azide. Highest yields arc obtatrr.J r be obtained in 2O-25Vc vic-ld frrvn
o
and I (20 mol
a\ t
ethcrs of propargylic alcohols in 92-97o/o ee.
rS. Kobayashi,H. Uchiro, Y. Fujishita,I. Shiina, and T. Mukaiyama,Am. Soc., l13' 4247 (1991)' 2 S. Kobayashi,A. Ohtsubo, and T. Mukaiyarna,Chem. Letrer.s,831 (1991). 3 T . M u k a i y a m a ,M . F u r u y a ,A . O h t s u b o ,a n d S . K o b a y a s h i i,b i d . , 9 t t 9 ( 1 9 9 1 ) .
c
l
+
RN3
R = n-l-ler R= Bt
o
/-''a"'" l l Titanium0V) chloride. Chlorotitanium enolates (16,332-334).r The titanium enolate of the N-propionyloxazolidone1, preparedwith TiCl+ and CzHsN-i-Pr2,undergoeshighly diastereoselective Michael reactionswith ethyl vinyl ketone, methyl acrylate,and acrylonitrile.
n-HexN3
5-1*
In some cases the ring crparx intermediate(equationI).
6i i\: N
.. ",Oot reaction of MukaiYama ,l.rrholsby reactionof acetylenic ;hiral catalYstis obtaincd bY a ::,'m (S)-proline,(S)-1-methyl-2.,.rion of an acetylenicaldehyde
?
o
H,,
o
o
qAN\.-A",,.', I \_-\ /
88"/o
CHS
Bzl 2 ( > 1 0 0 1: )
1
o
o
1 ) H 2 O 2O , H 2) cH2N2
't8 1
chloride
9
1)TiCl4,C2H5N(l-Pr)2 2) C2HsCOCH=CH2
oAr{',cH.
Titanium(IV)
cH,o\(\,Ac,H,
93o/"
CHs
This techniquecan also effect highly asymmetricintramolecularMichael addition,but in this case iPrOTiCl: is superior to TiCl+ and N(C2H5)r is the preferred base (cquationI).
?
?
(l) OAN\ \ l
l
arr,
\-2
l
2
coocH3 r-proricr3, Ol l N(c2H5)3,-78'
o
e
e
7
r.\
Y n f coocH3 r.r-\-{
q , u
"
Bzl (93 : 7)
(synlanti-95:5)
c ::. \cncc of Sn(OTf)2 and I (20 mol c .'.-,rhols in 92-97o/o ee.
Reaction of RNt with ketones.2 Ticl4 (2.5 equiv.) can effect a Schmidt type reaction of alkyl azides with cyclic ketoncs to afford N-alkyllactams.An aldol-typc reaction can also occur but can be supprcssedby use of excess(2 cquiv.) of thc alkyl azide. Highest yields are obtainedwith cyclohexanes,but ring expansionproducts can be obtained in 2O-25% yield from cyclopentanoneand cyclobutanoncs'
o
o
a\ t
\1 .,..ir\ama,Am. Srtc-,113,4247 (1991)' / : : ., ' . t t 3 l ( 1 9 9 1 ) . r r , r 1 19. t. t 9 ( 1 9 9 1 ) . r\'
.Ticl4, CH2C|2,0 - 20"
l
+
+
Nz
(_) R = n-Hex R = Bzl
80"/o a8%
o
o CHs
n-HexN3
5-19% t :::.rniumcnolateof the N-propionylr . :rndcrgoeshighly diastereoselective : - - r l . r t c .a n d a c r Y l o n i t r i l e .
An,,*
RN3
.A*'n-H"* / \
\ _fcH'
CHe. A /n-Hex Y - N +
|
\
+ N 2
1.7..1 \J
In some cases the ring expansion involves the rearrangementof an azidohydrin intermediate(equationI).
Titanium(IV) chloride
346
t
-
-
' -"l1A\.-. zo "' - lT - . t l = - ( / ^ o " o R"N \ -, , * ^ \ _ - / l r . r J l p:o
6 (r
l
Bicyclic enediYnes.o Ttx \t catalyzed Sakurai reaction of a o 3 as a single Product. This PruJu
l
(cH3)3si-...-
of TiCla' the (E)-vinylsilane (1a) reacts o-Hydroxy p,y-enoates.3 In the presence (E)-2a' in high yield' In with methyl glyoxylate to form an a-hydroxy-B'y-enoate' under the same conditions to give a 1:1 contrast,(Z)-la reactswith methyl glyoxylate The ene product' 3a is the exclusiveproduct mixture of (Z)-2aand the ene product (3a)'
n Y
r'\..Si(CHs)g ".r v " r |
*
quant'
coocH.
H
CHs
-
lt
Ticl4, cH2cl2,-78"
?"
o
(z\-1a
OH
I
cH.
(-coocH3 CHo (E\-2a
(E)-1a
\.,si(cH3)3 I CHs
H
+
llUl4'
cH2cl2
,A.oo"r. ?H. ?H \fcoocH. cHs
(cH3)3sit ?t - cHrl'Y'\coocH3 1:1
CHs
(z\-2a P d [ P ( C 6 H 5 ) r 1 4 ,C u l , a n d B u \ H '
catalyzedby SnCla' of reaction of (Z)-la with methyl glyoxylate S-phenylmenthylglyoxylate provides a with (Z)-vinylsilanes The reactionof (h,)- or single (2S)-alcohol (equationI)'
?u"u SI(CH3)3* \,.
(z)
t D.A. Evans, M.T. Bilodeau-T ('
(1ee1 ).
2J. Aub6,G.L. Milligan.and(- J 3 K. Mikami,H. Wakabavashr. enj a D. Schinzerand J. Kabbara.Srr
o
ll HACOOR*
o (>99o/" ee)
Titanium(IV) isoProPoxidcPnm 3-Amino-(,2-diokr to presenceof Ti(O-l-Pr)1 form
Titanium(IY)isoPmPoxide 347
c"o
Bicyclic enediynes.4 The key step in a synthesis of these enediynes is a Ticl+catalyzed Sakurai reaction of a conjugated allylsilane (1) with the enone 2 to provide 3 as a single product. This product, after conversion to the ketal, was cyclized to 4 by
f.fn
-N2
o (la) reacts l-. :hc (E)-vinylsilane high (E)-2a, in :n,,.,tc. Yield. In a L:1 ..rme give to conditions k N:.it. 3a is the exclusiveProduct
* (cHe)ssi--K--r. Ticl4 -74"
h
68/o
--\"
1
\
CHz
OH
-:
CH',.>.'\COOCH3 CHs
r) o..,,o (84%\ I ocH3 2\Pd(Ol, (24o/") Cul, BuNH2
(E)-2a
I
C H"" ) " S- |
I
t O Hl
cH/'fcoocH3 I CHs
4
3a
u -r SnCl,r. rnrlnrcnthylglyoxylateprovidesa
Pd[P(C6Hs)3]4,CuI, and BuNHz. This bicyclic enediyneis stable at 25"' I D.A. E ans,M.T. Bilodeau, J. Clardy,D. Cherry,andY. Kato,J' OrS'' 56'5750 T.C. Somers, (1991). 2J. Aub6,G.L. Milligan,andC.J. Mossman, J. Org.,57'1635(1992). 3 K. Mikami,H. Wakabayashi, andT. Nakai,ibld., 56, 4337(1991). a D. Schinzerand J. Kabbara,Synlett,766 (1992).
oR* 89'. (>99o/oee)
Titanium(IV) isopropoxide. 3-Amino-1,2-diols.t Primary amines react with chiral 2,3-epoxy alcohols in the presenceof Ti(O-i-Pr)+ to form 3-amino-1,2-diolswith high regioselectivity'
trifl ate
l-Toluenesulfonyl-3-methylimidazoliurn
n$/\on
9H
N H C"^ H -r r
C6H13NH2
I
Ti(o-iP04
* n---r/\oH I
nt^\/\OH : 6H
1,R =CoHs = cHs = Pr
NHC6H13
1J.F.O'ConnellandH. Rapopon. -/ rr't 100:0 93:7 92:8
83% 96% 51"/"
lM.Canas,M.Poch,X.Vcrdaquner,A'Moyano,M'APericas'andA'Riera'TetrahedronLetters' 32.693r (199r). (l)' N-(p-Toluenesulfonyl)iminophenyliodinane,CoHsI:NTs' Preparation.l this nitrene precursor ,qiiridination,2 Aziridination of alkenes can be effected with and cu(cH3cN)acloa particularly catalysts, cu(II) when catalyzedby various cu(I) and Cu(acac)2inyieldsof55_g5To.Notethataziridinationofasi|ylenoletherprovidesan
-
1 , C u c a t . ,C H 3 C N
---_--_.75 - Blo/"
\r
chromatography.
o
ll TotS:"AO l +
-EWG i CHz
1
N.
../ CHg"
3-(p-Tolylthio)-2-pyrone ( I ). Diels-Alder reactions.l l-Prnrr generally requiressuch high temlrrrr pressurecycloadditionshave alsrr trcr In contrast,this 3-substitutedd€n\ iln with electrophilicdienophilcsat l't - 9
l l \/
Ts u-3--Z\CoHs
p-Toluenesulfonamides and'stUt ondary amines into the arylsulfonam alcohols or phenols provides ar,rlsulfo scavengerimproves the yield.
EWG
-CoHs
NO:
C6Hs--l,CHz I osi(cH3)3
r'l
t .
CN cl-to COOClrr
o +
1,"';,t#1 -\
71o/o
CoHs-
v
-NHTs
N-substituteda-amino ketone (secondexample)'
* cH21
o tl o \__J
s 744
I Y. Yamada, and M' Okawara,Chem'Leuers'361 (1915)' T. Yamamoto' 2 D. A. Evans,M. M. Faul,and M. T. Bilodeau, J' Org'' 56' 6'144(1991)' (1)' preparedby reactionof l-Toluenesulfonyl-3'methylimidazolium triffate methyl triflate with p-toluenesulfonylimidazolein THF:
TfocH3
"r.O
(l -'
SOz
I
1\.
CHs
This Diels-Alder reaction can hc
even an unsaturatedspirolactonc.rrtl product of reaction of a-plrone rtrcl of COz.
(l) 3-(p-Tolylthio)-2-pyrone
p-Tbluenesulfonamides and -sulfonates' The reagent converts primary and secondary amines into the arylsulfonamidesin 7O-8OVoyields. A similar reaction with alcohols or phenols provides arylsulfonates.Addition of l-methylimidazole as an acid scavengerimproves the yield.
9H * n.^yloH
\J-
349
I NHC6H13
I J.F. O'Connelland H. Rapoport, J. Org., 57,47'15(1'992). 100:0 93:7 92:8 i' - ,- .rndA. Riera,TetrahedronLetlers,
|
3-(p-Tolylthio)-2-pyrone (l). Diels-Alder reactions.t 2-Pyrone can undergo thermal Diels-Alder reactions but generally requiressuch high temperatures(100-200') that the adductslose CO2. Highpressurecycloadditionshave also been effected,but the products are usually unstable. In contrast,this 3-substitutedderivative I can undergo thermal Diels-Alder reactions with electrophilicdienophiles at24-90" to give mainly endo-adductsthat are stable to chromatography.
\ I\. (l).
c .:rf ctcd with this nitreneprccursor and Cu(CH3CN)+ClOa s. I 'r-ticularly rr .:' ,'t a silyl enol ctherprovidesan
o to't\Ag \
(=*o 25.85">or4wc )
d-[
cH,
+
2 ( endolexo )
1 EWG NO,cN CHO
o
71o/o
CoHs-
coocH3
tl -\ v -NHTS 1
+
CH21,
o tl \_J
i: s6
98:2 2 : 1 98:2 3 : 1
82o/o 53"/o 44o/o 65"/o
6
,o',
2,Srot O o>(LA
74o/o
d-)-/
fJO
NaocHg86"/o
98:2
rr)l (1975). --+1(1991).
COOCH.
1l r. prcparedby reactionof
1 ) T B D M S O T f( 8 1 7 " ) 2) Bu.SnH.DBU (68%)
lllt:
o ,-V t t / / t - ,r\
R3S|O'
s9,
il
N+ I
CHs
-'
:\v ,O
4 This Diels-Alder reaction can be used to obtain functionalizedbicycloadductsand even an unsaturatedspirolactonesuch as 4 (equationI), which correspondsto the formal product of reaction of a-pyrone itself with a-methylene-y-butyrolactonewithout loss of CO2.
TFibutvl tin carbamate
The related 3-(tolylthio)-1-tosyl-2-pyridones(5) also undergo thermal Diels-Alder reactionswithout loss of an isocyanategroup (equationII).
o
ll o^. 2 9Tol e( TolS--ra-\ 'NSo2Tol O>(-!'--?,'CHO H-.*,.CHO c"rc', ( l l ) l l | + i l - - ; T o t s o z N { 42
\r'
bH"
This reaction can be extendedto r 7-halo ketonesby use of the stannrl r (2), prepared from Bu3SnOCH. arrl r stable trans-productspredominarc
ot l
-^ cHs- -(cH2)3ct - c€H
5 1G.H.Posner, J Org.,57,a083(1992);G.H. Posner, C.M. Kinter,andN. Johnson, T.D. Nelson, and K. Afarinkia,ibid.,57,4088(1992). V. Vinader, TFibutyl tin carbamate (1).
o tl
C"H^ l - -
- N --COOCH3 Bu35n-
Bu3SnOCH3+ C2H5N=C=O
DarZens-typereaction.t The Darzensreaction2of a-halocarbonylcompoundswith an aldehyderequiresa base, which can promote side reactions.Darzensreactionscan proceed under neutral conditions when effected with this neutral reagent (1 equiv.). Presumably,the reaction proceedsvia an organotin(IV) enolate. When the reaction is conductedin THF, the trans-epoxideis generally favored, but addition of HMPA can favor cis-selectivity.ci.s-Selectivityis also favored in reactionsof aliphatic aldehydes. The Darzens-typereaction can also be extended to a-halo esters,particularly in the presenceof BuaNF or LiBr.
o cH.AcHre,.
+
1 THF, 60' --.:,15o/o
C n H c C H e' C H O
o A CHs. V
3cH2c6H5
o
4Oo/o
c2H5o
= 61:39
o
o cH2Br
C6H5CHO
HMPA,60"
+
1 ,T H F
15o/o
+ BuaNF,-78"
8'|"/"
+ LiBr,25'
78o/o
il -A-
czHso-v
- cdq
'1. Shibata,H. Yamasaki. A. Baha.'r. H 2 M. S. Newmanand B. Magerlcrn. / >r' & Tlibutyltin
hydride. 3,4-Disubstituted tetrt,hfivtfr'l (CH3)3SnCl,NaBH3CN. and ..\,lB\ rl as I with carbocyclizationto 2 Orrft ammonium nitrate provides rtr etdd product isomerizeson treatmcnrrnt is convertedin several steps ro rlr lg
?"r. cH3olYocH3
cisltrans=4:96 + HMPA
cuHr^lcHr;ot
Dr,
^,, nuel-lc
o
cisltrans=60:40 = 58:42 =8:92
\s'rE
Y )
\o/
("^'
T[ibutyltinhydride 1.., Lrndergothermal Diels-Alder n : I li .
ro,SOzNN '
This reaction can be extended to a synthesis of disubstituted tetrahydrofurans from 7-halo ketonesby use of the stannyl iminocarbamateBu3SnN(C6H5)C(OCH3):NC6H5 (2), preparedfrom Bu3SnOCH3and C6H5N:C:]rIC6H5. In these reactionsthe more stable trans-products predominate.
) SIo, .\ // l/ ->l-*-r' _CHO
,
".
351
o
2,rHF,
cH.AlcHz)scr + c'HscHo +
"utt "la,,o)
.r.#-J o
5 7 , 4 0 8 3 ( 1 9 9 2 ) ;G . H . P o s n e r ,
cisltrans=38:62
'
C"H^ t - " - N ,- C O O C H 3 Bu3Sn-
,i ,'halocarbonylcompoundswith | :-.r!li()ns.Darzensreactionscan h :i:r. ncutral reagent(l equiv.). \ enolate. When the reaction is , :..i. hut additionof HMPA can '-.:.rions of aliphaticaldehydes. a,:.rl() cstcrs,particularlyin the
o ^r'CH2CoHs \ /
o
"'Yo)
o ll cuHu^lcHr;ot
+ c6H5CHo -*;
fro
coHs
cisltrans = 21 :79 rl. Shibata,H. Yamasaki, A. Baba, and H. Matsuda,J. Org., 57,6909 (1gg}). 2 M. S. Newman and B. Magerlein, Org. Reacr.,Vol. V, 413 (1949).
Tributyltin
hydride. 3,4-Disubstituted tetrahydrofurans,t Trimethyltin radicals generated from (CH3)3SnCl,NaBH3CN, and AIBN (14,313-314) add to allyl cinnamyl ethers such as I with carbocyclizationto 2. oxidative cleavageof the (cHr):sn group with ceric ammonium nitrate provides the aldehyde 3 without attack on the aryl group. This product isomerizeson treatmentwith DBU to the rrans-isomer(>23:l). This trans-3 is convertedin severalsteps to the lignan burseran4.
:lsltrans=4:96 = 61:39
ocH3 (CH3)3SnCl, NaCNBH3, AIBN
o
CH25n(CH3)3
-\ .''r_-f "C"H^ C,H"O\ /
o
("'"
o"
cisltrans=60:40 = 58:42 --Bi92
1) CAN (58o/") 2)DBU (82%)
Ttibutyltin hydride
""o"{o""
cH3o\
",.oQ-'.a-Qr "r.d
Y.cHo
'o2
(o)
Radical ring expansion of lt of an a;-bromoalkylchlorok!'renc r chain. Treatmentof this adduerr to a ring annelatedproduct RLlru reactioncan be used to appcnd -.
qj 3 +
Tetrahydrofurans.2 A new route to tetrahydrofurans involves cyclization of an alkoxymethyl radical derived from a homoallylic alcohol. Thc precursoris obtainedby conversionof the alcohol (1) to the (tributyltin)methylether (9,475), followed by Sn-Li exchange,and quenchingwith (C6HsS)2to form an a-phenylselenenylmethylether 2. Treatment of 2 with BurSnH (AIBN) generatesan alkoxymethyl radical that cyclizes
OH i
O |
H
//r-/-
4)(c6H5se)2>
S - -E- "C ^ H ."
\-/\ H
c6Hs"/----..\cH2
o
744
2
1
B u 3 S n HA, I B N c6H6,80"
o
\
1)KH 2) BU3SNCH2I 3)BuLi
coHs*cHz
Cl\,-(CH, tl C
,CHs
,,CH"
11 cuHr4o2
cuHr4o2 2.6:1
Radical ring expansion of qtr. by alkylation of a spirrxrcltfrrr'o BurSnH/AIBN in refluxins hcnra thc reduction product 4.
trans-s
cls-3
to the tetrahydrofuranwith cis-selectivity.Only traces of the product of reduction are observed. This cyclization can bc extendedto bicyclic tetrahydrofuransand to tctrahydropyrans.
H
a--.-l--.,
asecoHs \-"^\-.o
l t vT-/
p
o
A (-l
1) LDA 2) BrC}i:CF,C
83a
1
H
a' O
SeCuHs
caHs&cHz
'-*cuHu!
O---f"t.
O1-'"t.
*
auru-L.--,J
3 r{ 8.2:1
Ttibutyltinhydride
353
Radical ring expansion offused cyclobutanones.3 This reaction involves reaction of an ar-bromoalkylchloroketene with an alkeneto form a cyclobutanonewith an exo side chain. Treatmentof this adduct with Bu3SnH (AIBN) generatesa radical that cyclizes to a ring annelatedproduct becauseof relief of strain in the four-memberedring. This reactioncan be used to append7-, 8-, or higher-memberedrings to appropriatealkenes.
cH30
3
+
r:.-:.rn\ involves cyclizationof an r,: I fhc precursoris obtainedbY | .:hcr (9,475),followedbY Sn-Li ether2. .,,phcnylsclenenylmethyl
Cl.-.}r-(CH2)3Br tl
|
(CHz)sBr
IY'-cr
s" ,ofl
c
o
:lr,rrmethyl radicalthat cYclizes
-,,\-SeC6H5 9I c,H5MCH2
Bu3SnH AIBN
o 'l8o/o
2 ,CHg
11 \
cuHr4o/
Radical ring expansion of propenylcyclobutanes.a The substrates(2) are obtained Treatmentof 2 with by alkylation of a spirocyclobutanoneI with 1,3-dibromopropene. BurSnH/AIBN in refluxing benzeneprovides the tricyclic spiro ketone3 togcther with the reduction oroduct 4.
trans - 3 tc. ,'l thc product of reduction are
turansandto tetrahydropyrans. H
-'^.-f--\ '--.Fvt
p
'
+
5 a\ l l \-.-
o
1)LDA
l-r:cu*
2) BTCHzCH=CHBr a\ 8 3 o / o l \-"-
l
:CHZ
o1.'cHt )
CeHsN 3 ( 4oo/o)
8.2:1
Bu3SnH AIBN
l
o
H
r cHs
o
4 (457o)
Tfibutyltin hYdride
CHr tl
CHBr Bu3SnH, A I B N ,h v -
a!l/t"'
at\
+
q\"
er-,W@ cl
41"/"
5O/o
Reaction of BursnH/ cyclization and expansion of dichlorocyclobutanones.s AIBNwiththeadduct(l)ofthereactionofendo.6-vinylbicyclo[2.2.1]heptene-2with dichloroketeneresultsinfreeradicaladditiontothefreedoublebondandreduction 2 with ISi(cH3)r/ZnI2 results in of the remaining chloride to provide 2. Reaction of which is convertedto enone ketone, cyclic a-iodo transformationto a seven-membered 3 by DBU.
Bu3SnH AIBN
ether, souno
+ C|2C=C=O
90o/o
cb ButSnH insertion into aliPbr with aliphatic chromium carttrrs I I t t diastereoselectivity(4-13:I ).
9cH' (co)scr^Yc6Hs
hex^nE 66'
691
cH3
1
Znl2 1) lSi(CH3)3, 2) DBU > 92%
&asr*t 91
OCH.CnH" O
r - t - - l l
rCo)^CrZf*I
CHs \-.,,
/
71/o
/i
as 1' prepared as shown trom Spiroannelation.6 A spirocyclobutan-2-one such AIBN (2 equiv'' slow addition) and when treatedwith Bu3SnH methylenecyclopentene, (2)' und"rgoe. radical ring expansionto a spirocycloheptanone
I
< 8l\
Radical ring exPansion of cvcb to medium-size ring systems. Thus t cyclohexenone,on treatmenl u.ith Bu, in 787o yield.
Tributyltin hYdride
--/
o
?r,
.CHa
a\
+
b*,.,,
1) N(c2H5)3,cH2cl2
*
2)Nal B'/--'-YCO
-
CI
41"/o B u 3 s n HA , IBN ceHo'
95o/"
bn,tnes.5 Reactionof Bu3SnH/ with -r r: r lhicyclo[2.2.1]heptene-2 reduction and bond double I i:;r I .rirh lSi(CH3\fZnl2 resultsin c: ,1r. \\'hich is convertedto enone
"{)
b 2
Bu3SnH AIBN
58"/"
\
,Cl
o
r
BujSnHinsertionintoaliphaticchromiumcarbenes.lBussnHandpyridinereact compoundswith marked with aliphatic chromium carbenes(1) to form a-alkoxytin diastereoselectivity(4-13:1).
y'X 'cl
gcH, Bu3SnH, PYr'
QCH3 |
^,,
(co)su/Yvor15 1
cH3
hexane'65' -"t**
aursnlcuHu CHs
+ syn-2 77 123
anti - 2
9cH.?uH'? ?cH'?u"'? + sYnisomer Buss"'\lli rcoluc../ff 81"/" cHs \,
-
)
iL.i .r: l. PreParedas shown from ::'.: \lBN (2 equiv., slow addition) p : , r ,' n c ( 2 ) .
cHs \--J
9 3: 7
Radicatringexpansionofcyclohexanones,sThisreactionisausefulroute 1' prepared in two steps from to medium-size ring systems. Thus the precursor cyc|ohexenone'ontreatmentwithBurSnHandAIBNfurnishesthecyclodecenone2 in 78Vo Yield.
Tfibutyltin hydride
o tl
o A. l( -
1) LiSnBu3 HMPA 2) l(CH2)3CH(Br)CH3,
.l
75"/"
trans-Decalins.to traru-Dcc sutrstttutc methylenecyclohexanes ester group.
^\-.---.,,,.cHe l l \ B r
-v'
-SnBu3 1
cooczn /-]"'\ cHeooc--< ' \ A|
o
'' cLu
ll 9Hs
B u 3 S n HA, I B N CoHs,
a'^\3-.\ t
78%
l
\-.\-,'
1
2
This ring expansionis applicableto cyclopentenonesand cycloheptenones,but the yields are usually somewhatlower. It is not applicableto a,B-unsaturated lactones. Stereoselectiveradical reactions. Giese e/ al.e have found that radicals can show comparableto ionic reactions,and that the selectivity can be high 1,2-stereoinduction from cyclic to acyclic radicals. Thus the Bu3SnH radical proceeding reversedwhen providesthe only one isomer (2) with /rans-selectivity.The 1 dioxanone addition to the acyclic system (3) shows cls-selectivity. a corresponding with same radical
Radical cyclization of ocq estersI with BurSnH/AlB\ rn (E)-2, as the major prcJucr silyl)silane/AlBN providtr a mrr A different stereoselectirrtr.ttl initiated by triethylborarr O; .{ result of isomerizationoI tZ>2 In any case, this isomenzatxn cyclizations.
coocH3 OH O'
Bul,Bu3SnH hv,2o'
-\ - O
t
l
o2'{,CH" i l CHz
I
97"/o -
K2co3
oAo I
78v"
oM'cH^ t eu2
-
toot>A"r. I
osiR3
cHsooc-..,fcHs
(trans)
CHe
,
l
1 Bu3SnH/AIBN c6H6,80' oMS)3SiH/AIBN Bu3SnH/(C2H5)38
1 ) B u l ,B u 3 S n H hv, 20" 2) HgO+
t
Bu/
2 (trans/cis= >50 : 1)
1
lll ';-"t.
cH3ooc
fl-MS)3SiH/(C2H5)3P CHg
68o/"
Bu 4 (cis/trans= 42:1)
Radical reaction ol c*rJ o-iodoanilide such as I is ablc Thus on treatmentwith Bu.SnH
TiibutYltinhYdride
357
trans-Decalins.lo lrans-Decalins can be obtained by a radical cyclization of substitutedby an adjacent alkenyl bromide and a carboxylic methylenecyclohexanes ester group.
..---/CH" I Br 5nUU3
cooc2Hs
f__.1,., cH3ooc< I tgr h"- )
o
ll 9Hs
84"/o
t \-,,\.,'
l
rY)
CH3OOC/Y
CHe
a/\7\
cooc2H5
B u 3 S n HA, I B N C6H5CH3'
1
2
but the s .,rJ cyclohePtenones, p-unsaturated lactones. r' ,,. ,r :,,undthat radicalscan show ::.i that the selectivitYcan be -fhus the Bu3SnH radical c-rr' 'r rlr rvith /rans-selectivity.The r',,r. t'is-selectivity.
Radical cyclization of acetylenic esters,tt cyclization of ro-iodo-a,B-alkynyl esters I with Bu:SnH/AIBN in refluxing benzeneresults in the (E)-exocyclic alkene, (E)-2, as the major product. ln contrast, cyclization of 1 with tris(trimethylsilyl)silane/AlBN provides a mixture of (E)- and (z)-2, with the latter predominating. A different stereoselectivityobtains from cyclization of 1 with Bu3snH or (TMS)rSiH initiated by triethylborane/o2.Actually the high (E)-selectivity in BurSnH/AIBN is a result of isomerizationot (Z)-2 to (E)-2, promoted by BurSnH at high temperatures' In any case, this isomerization is an unexpectedexample of regiocontrol in radical cyclizations.
coocH3
lll ';."t. OH HOOC\ -,\ Y
(:-' 'c-:
cH3ooc\
..,coocH3
&"'
(,
'CHs
tl
'
1-"zcnt (zl-2
(E)-2
1
\_J
Bu/ (trans)
)H3ooc
Bu3SnH/AIBN C6H6,80"
82/o
98:2
(TMS)3SiH/AIBN
86"/"
34:66
Bu3SnH/(C2H5)sB
84"/o
60:40
[rMS)3SiH/(C2Hs)3P
85o/"
11:89
CHo
Bu 4 (cis/trans= 42 11)
Radical reaction of o-iodoanili.des.t2 The radical formed by reaction of an o-iodoanilide such as I is able to translocateto a radical a to the carbonyl group' Thus on treatmentwith Bu3SnH (AIBN, 80"), I undergoescyclization to a disubstituted
Ttibutyltin
hydride
o
R1
\_^
Bu3SnH,
N-CH.
c.rrra$lff
+
o
R2
I
A|BN. 800
CoHs OC2H5 2 (2.1:1) CHa t -
Ri
o\-t-"or^ CHs
w
|
R2
FcH2cH3
t B-Hydroxy ketonesfrom o.p<pry with Bu3SnHor b1 a tlrnnrl by photolysis The former reactionis particularll uscfulf
25
syn-2
1
(ll)
?.r.
9CHg
anti-2 >25:1
B u 3 S n HA, I B N Mglz
syn-2
+ anti-2
61% 1 : 4
3 Thus the ester3 in which the iodide is syr?to the alkoxy group is reducedby Bu3SnH and MgI2 with moderatesyn-selectivity. Diastereoselectivereduction of a-alkoxy ketones.ts Bu3SnH alone reduces these substratesin low yield. The reactivity is enhancedby additionof a basesuch as HMPA or
Radical deoxygenation of scc.a
-coHs
OH anti/syn= 75:25
3
Radical
deoxygenation
of sec.-alcohols,
d . - . ' r , , no f t h c s cc s t e n s( 1 ) w i t h :,.ruetion in thc presenceof hr: r .r'rr-selcctivity becauseof ''.-. n I cquiv.is prcscnt.How-
p-fluorophenyl
tr', ,ihcmistryof the rcduction.
slowest of all known derivatives.
)F -^
ocH3 I _coocH3
CoHs- Y . ,25 cHs anti- 2 .'25: 1
,s,^,2 + anti-2 1 : 4
| !: ,up is reducedby BurSnH IJL-,SnHalonereducesthese tr,'- ,t .r basesuchas HMPA or
Barton-McCombie
reaction,ztt
This rc-
action proceeds more rapidly with xanthates IRTCHOC(S)SCH:] than with any of the known phenoxy thiocarbonyl derivatives IRTCHOC(S)OCaHs]. Of these the unsubstituted phenoxythiocarbonyl derivative is slightly more reactive than the 2,4,6-trichloro- or the derivative. The pentafluorophenyl derivative, R2CHOC(S)OC6F5, is the
rS. Hanessianand R. L6ger, Synleu, 4O2(1992). ' V . H . R a w a l ,S . P . S i n g h ,C . D u f o u r , and C. Michoud,J. Org.,56,5245 (1991). 3 P. Dowd and W. Zhang, Am. Soc.,113, 937-5(1991). aW. Zhang and P. Dowd, Tetrahedron Letters, 33,':1307 (lgg2). 5 P. Dowd and W. Zhang, Am. Soc., fl4, 10084 (1992). 6W. Zhang and P. Dowd, Tetrahedron Letters, 33,3285 (1992). 7 E. Nakamura,K. Tanaka,and S. Aoki, Am. Soc., ll4, g7l5 (1gg2). d J. E. Baldwin, R. M. Adlington, and R. Singh, Tetrahedron, 48, 33tl,5(1992). e M . B u l l i a r d ,M . Z e h n d e r , a n d B . G i e s e ,H e l v . , 7 4 , 1 6 0 0 ( 1 9 9 1 ) . f 0 M. Kawaguchi, S. Satoh, M. Mori, and M. Shibaski,Chem. Letters, 395 (1992\. rrT.B. I-owinger and L. Weiler, J. Org., 57, 6099 (lgg2). 1 2 D . P . C u r r a n ,A . C . A b r a h a m ,a n d H . Liu, ibid.,56,4335 (t991). l3 J. R. McCarthy, D. P. Matthews, D. M. Stemerick,E. W. Huber, P. Bey, B. J. Lippert, R. D. Snyder, '7439(1991\. and P. S. Sunkara,Am. Soc., ll3, f a J. R. Mccarthy, D. P. Matthews,M. L. Edwards, D. M. Stemerick,E. T. larvi, TetrahedronLetters, 3r, 5449 (1990). 15E. Hasegawa,K. Ishiyama,T. Kato, T. Horaguchi, and T. Shimizu,J. Org., 57,5352 (1gg2). 16S. A. Hitchcock and G. Pattenden, Tetrahedron Letters, 33, 4843 (1992). l7 Y. Guindon, J.-F. I-evall6e,M. Llinas-Brunet, Horner, G. and J. Rancourt,Am. Soc.,113, 9701 (leel). r8 I. Shibata,T. Yoshida,T. Kawakami, A. Baba, and H. Matsuda,J. Org., 57,4O4g (1gg2). reW.P. Neumann and J. Pedain, Tetrahedron Letters. 2461 (1964J. 20D. H. R. Barton, J. Dorchak, and J. C. Jaszberenyi, Tetrahedron, 45, 7435 (lgg2).
362
TributyltinhYdride-OxYgen
TFibutyltin hydride-OxYgen' RX - ROH (reductive oxygenation),1 Reaction of an organic halide with Bu3SnH (2 equiv.) in the presenceof dry air in toluene at O-20' results in conversionto the correspondingalcohol in yields generally >70%.The reactionis particularly useful for conversion of allylic halides to allylic alcohols with retention. It is applicable even to tertiary or hindered halides. The transformationis believed to proceed through a
Tiibutyltin hydride - Tetrabul-r-lemrtReduction of ketones.t This r-rrrnt 25-60" without reduction of halo rutrrrr
selectively to the more stable trarrr-akrrh tc in the caseof a-methoxypropiophenr'ne react with an added electrophile(R\ ot R
hydroperoxide. OH
02 2 Bu3SnH,
c6HscH3 ' 0-20"
cuHuMBr
+ .-,-.,-)"-,zcHz \16n5
coHsMoH
14"/o
80o/o
?r.
CHq
o\ur, t l \,,
?rr.
/1oa
vI
81%
cH.AcH,
(r) "utul^ar. o
cH.AcH, 52.48
92tB
OH
Br 55"/o
euMcoocH3
/'-Z\ o
COHS
,uA7--coocH3
(ilr)
h'
a\ t
/ / \
l
OH
Bu3SnH G e H s C H s0'" , 84o/"
i * .
o
cyclization as shown in This conversionof RX to ROH can be extendedto radical equationsI and II.
(t)
Et
t
l
Tributyltin hydride activated br HIII ketones such as a-chloro ketones.
( 1: 1 )
I I. Shibata, T. Yoshida,A. Baba.and ll v.l
f-/-caHs
q
coocHs
(lr) e:'t-coocH3 l E. Nakamura' T. Inubushi, S. Aoki, and D. Machii, Am. Soc.,1r3' 8980 (1991).
TFibutyltin hydride-TiiethylbonrRa.dical cYclization to tmnrhfr erally cyclize to a five-membered nngcyclizeslo e tr't I [Bu.rSnH-B(C:Hs).tl of an ener presence The b. a and icals
TFibutyltinhydride-tiethylborane 363
'n ,,r an organichalidewith Bu3SnH ll lrr' results in conversionto the rc :r.tction is particularly useful for rr: :rtcntion. It is aPPlicableeven r. l.clieved to Proceedthrough a
halide. Tiibutyltin hydride-Tetrabutylammonium Reduction of ketones.t This combination (t1) can reduce ketones in THF at 25-60" without reduction of halo substituents./-Butylcyclohexanonecan be reduced selectivelyto the more stable trans-alcohol(equation I). The reduction is syr-selective in the caseof a-methoxypropiophenone(equationII). The intermediatetin alkoxide can react with an addedelectrophile(RX or ROCI) to form ethersor esters(equationIII).
OH
'oH *
cgtu)"'r'cH"
o rcna"cjJ
3=J=g
(cH3)3c'JA7--oH
14"/o
C'.
(79:21)
CHs
t
- --a .oH
?*.
(u) "utrl^"r. o
'\cH, JZ
?tr.
81o/"
cuHu-.,A"r.'.^ -"o I
OH (lOOVo sfn)
qO
o OH
o
.\Z\coocn, (ilr)
a\ l
oA"uru
OSnBus
l
a\ I I
c6H5cocl 93"/o
Tributyltin hydride activated by HMPA can reduce aldehydesand some activated ketones such as a-chloro ketones. rI. Shibata, A. Baba,and H. Matsuda,Chem.Letters'307 (1991). T. Yoshida,
coocH3
r r ' , , . .1 1 3 '8 9 8 0( 1 9 9 1 ) .
Tlibutyltin hydride-Tbiethylborane. Radical cyclization to trans-hydrindanes.t Although 1,5-hexadienyl radicals generally cyclize to a five-memberedring, the radical formed from the vinyl bromide 1 [Bu3SnH-B(CzHs):l cyclizes to a trans-hydrindane2 selectively, possibly via radicals a and b. The presenceof an angular methyl group does not prevent a similar
Tfibutyltin
hydride -Tfiethylbomne
H , c H 2 o s i R 3
l H p H 2 o s i R 3
cH"ooc H - \ I'n Ho----\o/-4oart
+ trans-s
Lo
cls-5
4 +1 + DIBAH
9 1: 9 2:98
86"/" 887"
tothetrans-disubstitutedethersiseffectedwithalmostashighselectivitywithDIBAH. rH. Kotsuki,Synlett,9'7(1992).
This sequencew?S ux-d :o rcp particularly interestingas an an'irm"d
(l)' Ttiethylsilyl hydrotrioxide, (C2Hs)3SIOOOH -78' (13' 228)' Preparationby ozonizationof tricthylsilane'at reagent(1) can cleaveterminal and this Oxidative cleavageof alkenes't Although higher yields can be obtained much internar arkenes,the yields can be row. However, ifthesubstratebearsanalkoxyoranestergroupevenremotefromthedoublebond (equationsI and II).
CHe
I -
OZ---...^\-z^-,
-3
C 6H5 -,..-.O,,gz'-,r-,, 4 1)1 2\ tialH,
(l)
CH3(CH2hCH=CH(CHz)zR'tL'^"'4>
CH3(CH2)7cH2oH
42o/o R = CHg = COOCHg 83ol"
(ll) RCH3CH=CH2 pf = c6H5 = CoHsO
I G.H. posner,C. H. Oh. and\A X Vrh
RCHzCHzOH 54% 76/o
2 that can rearrange to the This oxidation can be used to Preparethe dioxetane 1.2.4-trioxane3, a Potent antimalarial agent.
Ttifl uoroacetic acid - Trhlkl- Sr. Intramolecular ionic hyew3ct A (4). from 5'nrt secopseudopterosin stituted double bond of l. Hrdn'.tct less hindered face to provide thc utd CF3COOH gives a 2:3 mixturc t'f J
Thifl uoroacetic acid -Ttialkylsilane
' ',-H -^oB.l
+
tans -3
1,CH2C|2
C
-78'>
o
3 99.93 : 0.07 4:96
n
2 5go/oIFBU(cH3)2siorJ, -78' | V
+ trans-s
,,H "-Aogtt 5
9l:9 2:98
r'.: .'. high sclectivitywith DIBAH. This sequencewas used to prepare other related 1,2,4-trioxanes,of which 5 is particufarlyinterestingas an antimalarialagainstcertain strainsof P. falciparun cloncs.
- - . ' r 1 3 .2 2 8 ) . , :..ilcnt (l) can cleaveterminaland rn...h highcr yields can be obtained c\ - ' rcmotc from the doublc bond
CHr| OZ---.-* |
|
4
1)1 2) t-Bu(CHg)zSiOTf _ QH3 8 / "
C6Hs,-.../.O--z/----2 OBzl l-'-
cur(cH2)7cH2oH I G. H. Posner, Letters,32, 4235(1991). C.H. Oh, andW. K. Milhous,Tetrahedron
f2oH
t \ - i . r n c 2 t h a t c a n rearrangeto the
Tlifl uoroacetic acid-Tiialkylsilane, 5, 695;6, 616. Intramolecular ionic hydrogenation' One step in a synthesis of a diterpene, secopseudopterosin A (4), from 5-methoxytetralonerequireshydrogenationof the trisubstituted double bond of 1. Hydrogenationcatalyzedby Pd/C resultsin attack from the less hinderedface to provide the undesired3. Ionic hydrogenationwith (C2Hs)rSiH and CFjCOOH gives a 2:3 mixture of 3 and the desired 2. Even higher stereoselectivity
370
Tfifl uoromethanesulfonic acid/Bomn(III)
trifl uoromethanesulfonate
.-CHs .H
--CHs .H
SnCla,but the higheststererxrLc to the correspondingl.-3{iols b rA.P. DavisandS.C. Heganr.{r
I
cH3o
CHs
(+)- (S,S,S)-TriisopnopenderThis amine (NLr) can hc p (-)-(S)-propylene oxide.
cH3YcH3
E nantio sele ctive additia ol 1, formulated as (LZrOHl;-r-Br followed by additionof H;C).rz
h-.cH. cH.-..-,,-x.,,{
i l t l
^otfi
RO
CHs
+
4
reaction of can be effected by an intramolecularversion of ionic hydrogenation.Thus which on 1, of ether I with t-Bu2siHCl and imidazole (DMF' 23) provides the silyl yield 65-757o 2 in gives slow addition to cF:cooH followed by desilylation(BuaNF) in >95% purity. Letters,32, 1s.w. Mccombie,B. Cox, S. Lin, A.K. Ganguly,and A.T. McPhail,Tetrahedron (1991). 2083 Tliffuoromethanesulfonic acid/Boron(Ill) trifluoromethanesulfonate, TfoH/B(orf)3. This combinationprovides the BronstedsuperacidTfOH2*B(OT04-' l' 2 are obStereoselectiveallylation of alkorysiladioxanes,t Alkoxysiladioxanes tainedbyhydrosilylationofB-hydroxyketoncs(16,S2),usuallyasal:lmixture (CHr)3SiI' and of translcisisomers.The allylation is also catalyzedby (CHr)3SiOTf,
o H o
(80 - 90%) 1) Cl(,-Pr)2SiH 2) Bu4NH,CH2C|2,0' (95 - 98%)
,uSo"r.
l-Pr, ,l-Pr
o'Si'o
,,AA*r. 2 , ( 1: 1 )
CHz=CHCHzSi(CHs)e 1, CH2C|2,-50'
o" Oo
o CH.- \
'o
rW.A. Nugent, Am.S<x..lla. :'t
2, 4, 6-TFiisopropylbcnrcraJ Ch i ra I a -azido aq ISI -vctu in the peptideunit. The ongrnel arylglycinesvia an intc'rnrdrlr group on addition of acetrc r.r promote decompositionto .n I
I D.A. Evans,D.A. Evrard.S D I Letters,33.lllrq r19 Tetrahedron
i-Pra ,r-Pr
o'Si-o
85o/"
,r"\-\-',\"r, 3. lpns/6js = 23 : 1
Ttiisopropylsilyl enol etberr r Reaction with azidotri*t (CH3)3SiN3and C6H.lO (l cqo The azido group of 2 is di+le
Tliisopropylsilyl
enol ethers of cyclohexanones
371
leoeulfonate
un3
,CHS
H
.H
obtainswith l. The products(3) can be desilylated SnCla,but the higheststereoselectivity to the correspondingl,3-diols by treatmentwith HF in CH3CN' 1A. P. Davis and S.C. Hegarty,Am. Soc., ll4' 2745 (1992).
oH cH3o
CH.
CHs
(+)-(S,S,S)-Tfiisopropanolamine, [C H : C HCH2l3N. with This amine (NLr) can be PreParedby reaction of (+)-(S)-1-amino-2-propanol (-)-(S)-propylene oxide. Enantioselective addition of RjSiNj to meso-epoxides. A chiral zirconium catalyst l, formulated as (LZTOH)z+-BuOH and prepared by reaction of L:N with Zr(o-r-Bu)+ cleavageof epoxidesby R3SiN3. followed by additionof HzO, can effect enantioselective
.CH .F
o"
cH3. pH3
O"
* "tt-rt''*,
* "tr-I-t'-*.
{. of rn:. hrdrogenation.Thus reaction on which 1, )\ r,:.\ the silYl ether of or , llurNF) gives 2 in 65-75Va Yield Letters'32' d r I VcPhail,Tetrahedron
(cH3)3si(ococF3) r,'-\..'osiR3 1'o' r 8O"/"
t
9N.
CHs
l
93o/"e€
cH3 pH3 CHs
"'osiR3
/)
E4%- H*, 83o/oe€
on)methanesulfonate' a. :.: I fOHz*B(OTf)4-' f' are obt rd\. AlkoxYsiladioxanes2 mixture l : 1 a a s u s u a l l Y f i 2 ) , ;,16. and r/,.1 h\ (CHr)jSiOTf, (CHrlSiI' \ e 95 rs'.)p
l-Prr ,l-Pr i O'"'-O
r
au
l
'4oct-t. 2' (1:1)
'a
l :
fl^
I W. A. Nugent,Am. Soc., ll4, 2768 (1992). 2, 4, 6-Tiiisopropylbenzenesulfonyl azide (trisyl azide, l), 14' 327' chiral a-azido arylglycines.l Several glycopeptide antibiotics contain arylglycines peptideunit. The original methodologyfor asymmetricazidation(14,327) to give the in arylglycinesvia an intermediateN-sulfonyltriazene,can fail to decomposeto an azide group on addition of acetic acid. In such cases,addition of NaI or KOAc at 25" can promote decompositionto an azide. rD.A. Evans,D.A. Evrard,S.D. Rychnovsky, and K.M. DeVries, T. Friih,W.G. Wittingham, Letters,33, 1189(1992). Tetrahedron
Tiiisopropylsilyl enol ethers of cyclohexanones. Reaction with azidotrimethylsilane.t The triisopropylsilyl enol ether I reacts with (cH3)3siN3 and coHslo (1 equiv.) to form the B-azido adduct2 as the major product. The azido group of 2 is displacedon reaction with a number of carbon nucleophiles
Tiimethylaluminum
inthepresenceofaLewisacid.Theoverallreactionrepfesentsaconjugateaddition to cyclohexnone.
Pr)s
?si(''
a\
osi(t-P03 (cH3)3siN3 CoHslO ,
LiAlHl 99%
1,^Ns
(, 1
osi(,-Pr)3
a\
oSi(r-Pr)3
",ft18?.i1,", o ,",T1.,,1'"*-)
\tu'u
'o*f "*'=tttH2snBu3
imine 2, which is reducedby LiAlH. to t acids (TiCla, ZnCl2) can effect this rcarranc added,but the isolatedyields of 3 arc rn th effect conversionof I to 3 in 99'Z ricl,J. h{ Moreover, this reagent is superior to t{hcr
includingvery sensitiveenaminc:. Methylntion of Y, t-ePory ocr-rbct'' 7,6-epoxy acrylatesuch as I resull' tn i n
--cH,
f P . M a g n u s a n d J . L a c o u r ,A m . S o c ' ,l l 4 ' 3 9 9 3 ( 1 9 9 2 ) '
Ttimethylaluminum. Si-transferfromoxygentocarbon.|Inthepresenceofatrialkylaluminum'par. at -78' to 20' to csters of trialkylticularly (CHj)iAl, silyl kctene acetalsrearrange of Si from oxygen to carbon is the reverseof silylacetic acid. This 1,3-rearrangement of Si from carbon to oxygen' But RrAl the well-known Brook thermal rearrangemcnt2 does not rearrangetrimethylsilyl enol ethers'
^,, Jo""^' cHzl osi(cH3)3
"I,!iilj?r",(cH3)3sicH2cooc2Hs 84o/o
This reaction has seen 3-Aza'Cope rearrangement of N'a@t'N-allylenamines'3 (200-250). A variety of reagents limited use becauseit requireselevatedtempelatures this type' 1' to the unsaturated of enamine an of can catalyze the rearrangement
o t'trrr"A--z--cozcH3
A cht heraru
However, the same reaction u ith c;rrr the e or f position results in a singlc ;rt Al(CHj)3 (8-10 equiv.) in CH;CI; an<Jr (E)-epoxy acrylate(2) is convened crclus is converted into syn-3 in 93'/ ricld
Trimethylaluminum
f:-\.nts
a conjugateaddition
Ar(cH3)3/^\y,,'\NZ'.-"'CH3 | | l-cHs
NAc(cH.)2
\'o"',
\-/
cHzs,,/ 2
a--a,,"--il.^..!The rrtmr azabicyclo[3.3.1]nonan-2-one. carbamateto provide both (R)- or (SF2
13,5-Trimethyl-1,3,5-cyclohexanetricarboxylic
acid (Kemp's triacid)' I
f-BuO
OH
ezrO-.--,1-.rr,LCO2Et
HO
I
CHs anti- 3
(il)
',to
',to
81 - 98%
,o4-"r.
,o*-"r,
CHs
CHs
OH
Bzro--Aa\,/cO2Et
R = Ts, Ac, Bzl
CHs srn-3 reverse of that of simple diols (equation II).
e .,'ntiquouschiral centersin 95%
1 K. Maruoka, H. Banno, and H. Yamamoto, Synleu' 253 (1991)' 2A.G. Brook, Acct. Chem. Res.,7, 77 (1974). 3c.R. Cook, N.S. Barta, and J.R. Stille, J. Org', 57,461, (1992)' 4 M. Miyashita, M. Hoshino, and A' Yoshikoshi,ibid-, 56' 6483 (1991)' 5 D. H. R. Barton and J. Zhu, Tetrahedron, 48' 8337 (1992)'
9:'.
OH
OH
-,cooc2H5
-r {.
CH3 CH3
1,3,S-Ttimethyl-1,3,5-cyclohexanetricarboxylicacid (Kemp's triacid), l'
Supplier:Aldrich. This esteris commercially availablebut expensive.It can be prepared
5
t,;. ,,f l,2-diols on treatmentwith r., :rtlroxy t-butyl etherswith high
OH Ot-Bu
CHr\ ' COOCHa --\ |t |l -CH3 cH3--N.'{ COOCH3 CH3OOC
(1)
ao"' "Aon 0 - 1O"/o
a -rnrplc methodfor monoprotection ri:rJratcs regioselectivitycan be the
acid. by trimethylation of 1,3,5-cyclohexanecarboxylic curran, ReChiral auxiliary for asymmetric radical addition and allylation bek et al.t have prepared the chiral auxiliary 2 from I by manipulation of the carboxylic acid groups to provide 1+)-2, endo-l-(2-benzoxazolyl)-1,5'7-trimethyl-3The racemic auxiliary is then resolved via its menthyl azabicyclo[3.3.1]nonan-2-one. carbamateto provide both (R)- or (S)-2.
1.3.5-Trimethyl-1,3,5-cyclohexanetricarboxylic
acid (Kemp's triacid)' I
o (\,
{ll) CHa *
o/v 'Y/*'F,'i
cH3/coocH3
l
o
CHe
CH: (s),96 a
( x )- 2
o
:N
I J.G. Stack,D. P. Curran,S.V. Gcrh.J Rs.
1 Pe-s
,\ -CH" CeHs- Y : OH
5 4 : 5 : 6 = 7 8 : 1 9: 3
.o B-stereoselectivityinradicaladditions.Theoriginoftheregioselectivityisuncertainbut may result from inhibition of a-substitution' Thisauxiliarycanalsocontrolthediastereoselectivityofradicalallylation (equationII).
c6Hs''\i-cH3 ee 97'Yo
Tbimethyl orthoacetate I tn!( id r. I
o
(il)
A,V r ._rr"FJ
tl CHg\-A.*
*
l
^
I
AIBN C6H6,80"
c^ /t-aSnBu3
o "tr#x* -
flJ-cns CH:
l
34"/"
o cHrs-..\r^oH -lg9!* A l CHs (S),cro+10.5'
CHs ( S ) , 9 6: a
:)-2
z\
I i l "'\-/ " t - \H '-* Am. Soc.,ll4,7007 (1992). I J.G. Stack,D. p. curran,S.v. Geib,J. Rebek,Jr.,andP. Ballester,
-:.--^cH. J
2 . - - 7. 4 " p - - rcosclcctiveaddition to fuh.':. lrt control both regio- and
Tiimethyl orthoacetate, CHrC(OCHr)r. Epoxidesfrom 1,2-diols,l A one-potconversionof 1,2-diolsinto epoxidesinvolves This conversionto an orthoesterI by acid-catalyzedreactionwith trimethyl orthoacetate' with (cHr)rSicl and iodide or bromide, chloride, derivative is then treatedwith acetyl provides cyclization and hydrolysis Base-catalyzed inversionat the halide centerformed. thc epoxide with a second inversion.
u i _
F.
! -
;:
o
ceHso)f^y4". r. . O
cH3 pcH3
9H ^ -cH. CoHs- Y :
cH3c(ocH3)3 PPTS
OH
oXo \"r,
c.Hu
t-Bu
I I n"cr
| (cH3)3sicl
I
I
J
tl'- :rciosclcctivity is uncertainbut j..i,itivity
of radical allylation
..o CaHu"^-'-;"CHs 97o/o @a
cl K2CO3,CH30H
)'-.,r",, : 6nc
CoHs
Tlimethylsilylboron
OH I /,-_*.CHs
l
R3SiO
trifl ate
1)cH3c(ocH3)3 2) AcBr,(CH3)3SiCl
Qr CHs
,a"-,a"r" l l R3S|O OAc
+
l
OH
Addition of CHz:CHCHtSircHt b I a Lewis acid (1 equiv.), or a superrid lk catalyst, a "supersilylating" reagent I A. P. DavisandM. Jaspars, Anget.( lvr tt
8 5 : 15
I 83% K2CO3,CH3OH
l(lhimethylsilyl)ethynyll-9-BB\ Preparation:
| l r.
| i
/'r
y'Lcu" (CHg)sSi-Li
R3SiO
+ g11.g-g^
\-/
59o/oee 1H.C. Kolb and K.B. Sharpless, 10515(1992)' Tetrahedron,48' Tfimethylsilyl azide-Iodosylbenzene. (CH3)3SiN3- C6HsIO (1, 2: I )' -45" to form CaHsI(Nr)2,which decomposes The reagentsin the ratio 2'.7 reactat at 0' to CcHsI and 3Nz. triisopropylsilyl enol ether 2 with B-Azido triisopropylsilyl ethers.t Reaction of the L (2:l) at -45. gives two products,3 and 4, as a 1:1 mixture. Addition of 2,6-di+-butyl4-methylpyridine(BMP) to this reaction gives 3 and 4 in the ratio l:4. The product 3 can be obtainedin>95% yield by reactionof 2 with coHsI:o and then (cH3)rSiN3 at
OSi(iPr)3
osi(i-P03
a>
+
-45' 1, CH2CI2,
r.rrrir
\-/
N3 psi(iP03
rt-r*' t l
ftattll meta-Selective Diels-Adcr trimethylsilylvinyl-9-BBN, but it rcr-ts r quantitativeyield. The regiochemrstn r r preferentially over the para addtrls
(cH' - 'E + t | CHz RsSio R3 = (CH3)2-t-Bu 1)HOA. r73i 2) DDO r7.t
4
2
J
+ BMP
4'.1
25". This unusual B-azido functionalization of triisopropylsilyl ethers is a although the best conditions show some variation with the structure reaction, general ether. silyl of the enol I P. Magnusand J. l-acour,Am. Soc.,114' 76'7(1992)' -15. -
Ttimethytsilylboron triflate' (CH3)3SiB(OTf)4. The reagentis preparedby addition of (CH3)rSiOTf in CHzClz or CHCI: to freshly prepared B(OTf)3 (obtained from BBr3 and 3HOTf).
I D . A . S i n g l e t o na n d S . - W . I r u n g . . / t m
51
Tfimethylsilyl trifl uoromethencsrilrr* 1,2,4-Trioxan-S-ones.t -1.6.f'Trnnr paredby condensation of trimethrlsrlrla. ketones. These precursorsare obta.rrrri t't 1 acetals (2). The triflate I is an c'rscntrel
Tfinethylsilyl
Br = .CAl .,.",-.CHs + l l RsSiO OAc r
379
trifluommethanesulfonate
to RCHO.I This reaction requires fluoride ion, Addition of CH2:CHCH2Si(C& a l-ewis acid (1 equiv.), or a superacid.However, this reagentis a particularly effective "supersilylating" reagent. catalyst, a I A. P. Davis and M. Jaspars, Angew.Chem.Int. Ed., 31, 47O(1'992).
8 5 : 15
.:"" I xrco.,cH.oH
[(ftimethylsilyl)ethynyl] Preparation:
-9-BBN (r).
+
n
.1f,.cn,
BF3 O(C2H5)2
(CH3)3Si:-r-i
l : So
THF
+ CH'O-B)
,"r"rr",2'
59o/"€€
1 c:
,l{ lo (1.2:1). t lt.l(N:)2, which decomPoses enol ether2 with 1y1r.,'propylsilyl ir:::: .{ddition of 2'6-di-t-butYlI rr :hc ratio 1:4. The Product3 - l l l : O a n d t h e n( C H r ) r S i N :a t
N3 psi(i-P03
3-'
meta-Selective Diels-Alder reactions.t This alkynylborane is less reactive than trimethylsilylvinyl-9-BBN, but it reacts with 1,3-dienesat 100' to form adducts in quantitativeyield. The regiochemistryis unusual becausethe meta adductsare formed preferentially over the para adducts.
si(cH3)3-l
("r,+ 1 100", f R3sioAcH,
n
LR3sio"'-'-"\BBN
j
R3 = (CH3)2{-Bu 1) HOAC (73ol") 2\ DDO (74%\
f..,1si(cHor. R3SiOry
r ,: triisoproPYlsilYlethers is a j'1-.,srariation with the structure
[: :: ('t{-Cl2 or CHCIr to freshlY
I D.A. Singleton andS.-W.Leung,J. org.,57,4796(1992)'
TFimethylsilyl trifluoromethanesulfonate, (CHi)3SiOTf (l). 1,2,4-Trioxan-5-ones.t 3,6,6-Trisubstitfied 7,2,4-trioxan-5-ones(4) can be prepared by condensationof trimethylsilyl a-(trimethylsilylperoxy)carboxylicesters3 with ketones.Theseprecursorsare obtainedby photooxygenationof the correspondingketene acetals(2). The triflate I is an essentialcatalyst for this condensationand cannot be
Tf imethytsilyl trifl uoromethanesulfonate
r-n,,.VoSi(cH3)3 I osi(cH3)3
C6H5CHO + C6H5CH2OS
O-OSi(CHs)s
v2
, rr\osi(cH3)3
(cH3)3$ort
o
2
.\
1, (cH3)2c=o
92%
FH.
?."_f_"r.
This reaction can show signihr-ent d
,.ru\o
cHo *
o (t)
4
1c"1rso'
products,but is rep|acedby BuaNF. This ring system is rare|y encounteredin natural antimalarial' potent presentin artemisinine,a Acetat-8, p-diglucosides.2 In the presenceof trimethylsilyl triflate, trimethylsilyl-78" to form (1) reacts with aldehydesat 2,3,4,6-tetra-o-acetyl-B-o-glucopyranoside 2 in 3O-857o yield. At higher temperatures,mixtures of acetalacetal-B,B-diglucosides obtained'The yields arc dependenton the 9,9-, a,9-, and a,a-diglucosides are Ketonesdo not undergothis reaction. aldehyde. of the bulk reactivity and steric
( .OAc AcO-W
I
o
-^
,
(cH3)3siorf
/-'r.z^''I
I
This modified Sakurai reactxro hs I and -ketals by use of a bis-srlrlatc,j cd
(cH3)3siorf
-oSi(cH.)" + RCHo
nco-*or
(
-'?"
'
(CH3)2C(OCH3)2 +
30 - 85"/o
(cHd3s'o'/ t
OAc 1
l
l
(^-koc2H5 \r
TiCla-catalyzed Modified Sakurai reaction.3 The original reaction involved the and ketals to acetals the or ketones and aldehydes to allyltrimethylsilane addition of extended this form homoallylic alcohols or.ethers (7,3"10-37I). Mark6 et al. have of allylreactionto a synthesisof homoallylic ethersby a Lewis acid catalyzedreaction trimethylsilanewithacarbonylcompoundandatrimethylsily|ether.
+
1
(ch! lson
&a
OCzHs
Reaction of crotykilancs rrrl rri Noyori reactionof allylsilanessrth xt 440) to optically active (E)-crotrlsrl'rt (E)-hexenoates(1). These (EFcrtrr}ri rearrangement(6,276 - 277) of oprtxrllr
Ttimethylsilyl
trifl uommethanesulfonate
CoHsCHo+C6H5cH2osi(cH3)3+ cH1""-"si(cH3)3 O-OSi(CHa)o
ocH2c6H5
(cH3)3sioTl
,ur\osi(cH3)3
o .' . - C c HH: .
( ) a
c6H5,.,.,.$cH2 (equation I)' This reaction can show significant diastereoselectivity
c QHs
a'-y.CHO
( r ) l l \-/
cH Z"'.'si(cH3)3
T
(cH3)3sio'^c6H5
9t'
9t' but ls l-"'.:ctl in naturalproducts' rr:'- , :hr lsilyl triflatc,trimethylsilylat -78" to form 1. ..::h altlchYdes mixturesof acetall.' .:rtPcraturcs, ' dePendenton the are r iclds I ' reaction' ,i this uno>A* l- tl ll ) |I illl |\..''--Nf -to, -, \_/.-
VNoz
Y2
1 R = CsHsCHz = cHs = HC=CCHz
i
H
oxidant to date is benzeneselenrnx in the presenceof l, converls.rr-r This radical epoxidation is su;r'rxv of 1,3-dienes,such as l-r'inrkrclrt bond is selectively epoxidizcd .{ l
(')a> atr)
54"/"
7O/o 45% 56%
Tiis(4-bromophenyl)aminium bcrrct Radical epoxidation.t In rhe g can effect epoxidation of stilbrne. ht of the catalyst. Selenium dioridc rS epoxidation, but suffers from hrr r
41o/o
rw. R. Roushand X.-F. Lin, J. Org.,56, 5740(1991). 2J.E. MacorandJ.M. Wehner,Tetrahedron Letters,32,7195(1991).
CH
\-.-
BSA 1 Ttiphenylphosphine - Diisopropyl azodicarboxylate. Mitsunobu reaction of B-hydroxy-a-amino acid peptides.t Reaction of the Cbzprolyl-threoninc N-methyl amide I with P(C6H5)r and DIAD provides the peptide aziridine 2 in 84Vo yield.
o
H \ .N=J/'-NHCH3
i
\ru\\
fH 60. b .FoH
o
clc6Hlco3f{
of 4-isopropenyl-1-vinylcyclohercrx r o
o
6He\
tt il P(c6H5)3.oDlAD /^>/-N_-'..n\*rCr.
--;;-
\-,{ 'coz v
6g,
1
(tt)
I
2
cn/\c++, In contrastallothreoninepeptidesare convertedby the rcactioninto oxazolinederivatives (64-83% yield) with no aziridine formation (equationI). Oxazolines are also
(t)
cH3rcHs N)90%. Thc rcr-r diastereoselectivity.
Ttis(p-chlom)hexakis(tetrahydmfuran)divanadium
i. -:nrovedby reactionwith I -- \'litsunobureactioncan '- () bonds. Thus o-nitroll:..rn()buconditionsto form 1 ^, .'()nvertedto indoles(3).
hexachlomdizincate (l)
Tbis(4.bromophenyl)aminium hexachloroantimonate, (p-BrC6Ha[N+ SbCl6- (1). Radical eportdation.t In the presence of this radical cation, iodosylbenzene can effect epoxidation of stilbene, but only in low yield becauseof decomposition of the catalyst. Selenium dioxide (SeOr) is a suitable oxidant for this catalyzed epoxidation, but suffers from low solubility in CHzClz at 0". The most useful
tl
oxidant to date is benzeneseleninicanhydride, (C6H5S)2O (BSA). This oxidant, in the presence of l, converts cis-stilbene to rrcns-stilbene oxide in 85Vo yield. This radical epoxidation is superior to m-chloroperbenzoic for monoepoxidation of L,3-dienes, such as 1-vinylcyclohexene (equationI). Moreover the endocyclic bond is selectively epoxidized. A similiar selectivity is observed in epoxidation
:"b^,
(')a)
s
"t')
1'
{
I a\ (,
\-,-
/.
BSA,1 Rcactionof the Cbzidt,. l)l \l) pK)videsthe pePtide
760/o
55"/o
clc6H4co3H
21o/o
24o/o
of 4-isopropenyl-1-vinylcyclohexene (equationII).
c *'t
o
"t')
ll 'N.-7'"'-NHCH.
N
V Ccz 66, 2
(tt)
BSA,1 cH2ct2,o'
",x" .)
72"/"
H3
c.:.:i,\n into oxazolinederivar:: : l). Oxazolinesare also
CHs
'-..\-..,..*onc o'
c6Hs/-\-,\'-'-oH
hexachlomdizincate (l)
3 VCl3CrHfl3 l z
-C
2 OH
t l cH.-f\,..---Monc " c t I
C6H5 --r..\..--.,OH I CHg (anti/syn= 31
CI
HO\/CHzOH
93:7
3 (81ol")
o"
?'.
* cH.-f,)(*on"
OH
'l)
c. .,,upling with ketones,but bY ri ' 1n. coupling betweenketones
c.Hu
?'.
CHe
CHq
80%
cH.
HO\ PH2OH
/-Y"'"
Asymmetric 1,4-diamino-2,3-diols.3 (S)-N-Cbz-aminoaldehydcs2 undergo pinacol homocouplingin the presenceof 1 to afford (lS,2R,3R,4S)-1,4bis(Cbz-amino)-2,3diols (3) in good yield and high diastereoselectivity.
\-, (8:1) ,c" -n()\idesto alkenesin 5O-98Va . ,:'.i thc cis-configurationof the
-
.) \
.
\"'cH' CHg
o
tl R'-.,,\| " NHCb (s)-2
1 ) 1 , c H 2 c t 2 ,2 5 ' 2) H3O. 87"/"
l
CbzHN
l
N HCbz C
t
R
OH
-3 (2s,2R,3R,4s)
R=i-Pr
89o/"
R=l-Bu
61"/o
R = CHzCoHs
76"/"
(Y''coocH3
1ca.l3Cry lF , , i cquiv.) affordsthe halohydrin
OH
-h---A--A.t
1 J. Park and S. F. Pedersen, Tetrahedron, 48, 2069 (1992). 2 T. Inokuchi, H. Kawafuchi, and S. Torii, Synlett, 510 (7992). 3 A . W . K o n r a d i a n d S . F . P e d e r s e nJ,. O r g . , 5 7 , 2 8 ( 1 9 9 2 ) -
394
Ttis(phenYlthio)nethane
Tlis(dibenzylideneacetone)dipalladium, Pdzdbar' Allylic gem.-dincetates.l In the presenceof this Pd(0) catalyst, propargyl acetates I)' react with acetic acid to form (E)-allylic gem-diacetatesin 55-797o yield (equation prepared. be also can gen-dicarboxylates Mixed
HC(SC6H5)3+ 1
An intramolecularversion of this reactioncan result in macrolides(equationII)' nucleus 2 as a single cri. .urnhirsutene(3) by kno*n srcpl .
OAc
(dba)sPd2'CHClg CoHo, P(CoHs)s, . 52"/"
7
o ( 1 . 5: 1 )
I
I K. Ramig,M. A. Kuzemko.X r& or stille reaction The preferred catalyst for this coupling of unsaturated halides catalysts effective more Much Pd[P(C6Hs):]+. has been triflates with organostannanes a PdLn can be obtainedby treatmentof Pdzdbarwith 4 equiv. of various ligandsto form and (TFP)3 tri-2-furylphosphine are effective most catalyst.2Of a number of ligands,the triphenylarsine[As(C6H5)3]. I B. M. Trost,W. Brieden,and K. H. Baringhaus, Angew.Chem'Int' Ed'' 31, 1335(1992)' 2V. Farinaand B. Krishnan, (1991)' 9585 f13' Am. Soc., 3 D.w. Allen and B.F. Taylor,J.C.S. Dalton,51 (1982). Tiis(phenylthio)methane, HC(SC6H5)3(1). r This reagent can function as a dilithiomethane [2+1+2]Cyclopentannelation oxidized equivalent in consecutive conjugate additions to form a dienolate that is triquinane the obtain to used been has cyclopentannelation This to a cyclopentane.
TFis(trimethylsilyl)sibr rI r Review.t ChatgiliakStu I radical reducing reagenls ()n
the strength of the Si-H can t [(CHr)?Si]2SiCHrH slrcu's tlrh The silane I is useful for rcrjr.rcr in the presenceof onll smell r and purification of the prrrdtrt3 useful for radical reduoioo ud Selective hydrogcn otn . radicals such as 4 abstract hrdr observed by Cram for redrrtxn
Tris(trimethylsilyl)silane(l)
ru. tr.irrl) catalyst,propargyl acetates tr:.. rn 55-79Vo yield (equationI)'
9_,,-
oAc
*to-r-$oo.
fiz
1) BuLi 2) sec - BuLi
*{-"". HC(SC6Hs)3 1
r, :icr3
o
o
Lio
\ -lt oLi
l
\-"t.6!.rr.l Y""trl c6H5s sc6Hs
'""^?i 64"/"
f"t. \-./.cn.
CHe CHs
_l
r..-i: rn macrolides(equationII)' nucleus 2 as a single cis, anti, cjs-2. This triquinane 2 has been converted into (+)hirsutene(3) by known steps in l8o/o overall yield from l.
osiR3 CHs
o
CHe
( 1 . 5: 1 )
rK. Ramig,M.A. Kuzemko, J. Org.'57' 1968(1992). andT. Cohen, K. McNamara, halidesor rr- .,ruplingof unsaturated r, Much more effective catalysts {. , pn ,,l various ligandsto form a PdLa r. .,retri-2-furylphosphine(TFP)3and . , ,., ttt.Int.Ed-, 31, 1335(1992)'
): t_
:n: ..rn function as a dilithiomethane t., rLrrm a dienolate that is oxidized s ^Jcn used to obtain the triquinane
TFis(trimethylsilyl)silane (l). Review.t Chatgilialoglur has reviewed the use of organosilanes,particularly l, as radical reducing reagents.One advantageof organosilanesas rcducing agents is that the strength of the Si-H can be modulated by a choicc of substituentson Si. Thus donor, [(cH3)3si]2sicHrH shows only about lo%oof the reactivity of I as a hydrogen The silane I is useful for reductionof halo, NC, and SeC6H5groupsat room temperature in the presenceof only small amountsof radical initiators. For this reasonthe isolation and purification of the products is simplified. Tris(alkylthio)silanes,(RS)iSiH, are also useful for radical reduction and for hydrosilylationof alkenes. Selective hydrogen atom abstraction by radicals. Giese and Curran2 note that radicals such as 4 abstracthydrogen atoms in a ratio that is remarkably similar to that observedby Cram for reductionof ketonesby lithium aluminum hydride.
Tiis(trimethylsilyl)silane(l)
o tcHs)rcHlAcHs
OH I
(cH3)2cH )A"r.
CoHs 2
OH
-..1AcHs * {cHs)zcH
CH3-.."...CH3
,
A2'
CoHs
CoHs 13.3:1 syn-3
anti-3
I t, u"uo"=*or-tu
I
osilsi(cH3)313 I
HzsctzsH'
(CH3)2CH\,-\(_H^ -"r |
CoHs
syn-3 + '|2.6:1
f--r'cH' o h.r,
anti-3
63\
4
Hydrosilylation of alkenes and allqtnes.' This reaction can be effected with I and an initiator at 90'. Reactionwith monosubstitutedand gem-disubstitutedalkenesshows high anti-Markovnikov regioselectivity. cis- or ,rans-Disubstituted and trisubstituted alkenesare hydrosilylatedin high yield but require longer reaction times. RCOCI AIBN
RH.o
or tert-acid chlorides. C6H5CH=CH2
. A%I B - -1i 4 *N
(cH3)313 c6H5cH2cH2silsi tutuy^silsi(cHa)3r3
c6H5YcHz
CHs
CHs CHs
Ia
04oAo
a)
cHs
n
o4oAo
,silsi(cH3)313 cHs
.
x
,silsi(cH3)313
This rerrrn.r
in dodecane or toluerr Reducrin
.t rtr'
r
o{ prr
coproducts.
I C. Chatgilialoglu, Acc. Chem Rar l. i.tl 'B. Giese, W. Darnm, J. Dickhaur t nt{ 6097 (1991). 3 B. Kopping, C. Chargilialoglu.\l Zrbtu_ 'M. Ballestri and C. Chargiliak13lu \ (r (1e92).
16:1 o4oAo
- (L*si(cHo)st3."(> CHS --r-1"/" 51 : 4e SilSi(CH3)313 II (z) (E) H
Tirngsten carbene complexes. Aminocarbene Diels-AUcr n-i chromium carbenesto undergo Drcls-.1 acid catalyst (12,135- 136) has prnng.c aminocarbenecomplexes.Unfonunerch t alkoxy counterparts.But the (EFamrla c with Danishefsky'sdiene at 90' ro enc high exo-selectivity(>25:l). Houocr d
T[ngst€n carbene comPlexes
silsi(cH3)313
OH ctl --AcHs
cH3---,.cH3
4t2""
CoHs
82"/o
anti-3
CHs
,r--/CH'
o h.r,
/-l^tilsi(cH3)313 HcH.
:fl.;lcd with I and rtr.: .rlkcnesshows .i1.1 trisubstituted ln ..
RCOCI - RH.a This reaction can be effected with this silane in combination with AIBN in dodecaneor toluene at 80" in high yield, particularly in reactionsof secor tert-acid chlorides. Reduction of primary acid chlorides leads also to aldehydes as coproducts. rC. Chatgilialoglu,Acc. Chem. Res.,25, 188 (1992). 2 B. Giese, W. Damm, J. Dickhaut, F. Wetterich, S. Sun, and D. P. Curran, TetrahedronLetters, 6097 (1991). 3B. Kopping, C. Chatgilialoglu,M. Zehnder,and B. Giese,J.Org.,57,3994(1992)4 M. Ballestri and C. Chatgilialoglu, N. Cardi, and A. Sommazzi, Tetrahedron Leners, 33, 178'7
J
(
s [si(cH3)3]3
(1992t.
Ao
i, CHs)gls
T[ngsten carbene complexes. Aminocarbene Diels-Alder reactions.l The known ability of alkenyl alkoxychromium carbenesto undergo Diels-Alder reactionseven in the absenceof a l-ewis acid catalyst (12,135-136) has prompted an investigationof Diels-Alder reactionsof aminocarbenecomplexes.Unfortunately thesecomplexes are much less reactive than their alkoxy counterparts.But the (E)-amino complex I does undergoa Diels-Alder reaction with Danishefsky'sdiene at 90' to give 2 in 72Vo yield. Surprisingly,2 is formed with high exo-selectivity(>25:1). However the (Z)-isomer of I fails to undergothis reaction.
Tbngsten carb€ne complexes
NHCH3
ocH"
(co)swl/NHCH3 + = (E)-1
CH3
(co)5w 90"
)
(co)sw
I
AcH, R3SiO 2,(exo/endo=>25:1) CnH"
9{
n J - -
zcoHs
I
(co)4w1/NCH3
a
+ carbene comptex (22/")
: i^"."r0.=1
C H s R3S|O-
--CHz
3
4, 33o/o(exo/endo= 35:1)
Cycl& diphenyla
The chelated carbene3 is even more reactive than (E)-l and shows even higher exo-selectivity,but unfortunatelyis relatively unstable. Intramolecular bis-allqne annelations.2 A typical reaction of this type generally leads to a mixture of a phenol and a cyclohexadienone(equationI). However this annelation can be adapted to a construction of the steroid ring system by a
9Hs co (l)
(CO)5Cr
stable lsonx in the prcs.
cH3cN,70"
o ' CH3O
Diels-Alder reactionof the tungstencarbenecomplex I with Danishefsky'sdiene (1.5 equiv.) in acetonitrileunder CO to give the complex 2 in 62% yield.
) > CoHs
tion, but um. of a substitu
Tirngsten carbene complexes
OCHr
co)5w (co)5w
cH3O--
+
)
I
+
AcH, (cH3)3sio
cHccN.100" 62y"
2. @xo/endo= >- 25:1) CoHc / " -
RO 2
co)4w: + carbene complex (22o/o)
c H 3 O --
R3SiO 4 g3/" (exo/enle = 35:1)
i.:: tli)-l and shows even higher llr
ipri.il reactionof this type gener)( \.1(licnone(equationI). However .,1 rho steroid ring system bY a
lR=Hor(CHo)3Sil cycloheptadienones.3 The cyclopropylcarbene-tungsten complex 1 reacts with 2, which rearrangesto the more diphenylacetyleneat 100'to form a cycloheptadienone
l\---1 t/
.w(co)5 C 6 H 5 + C 6 H 5 \
dioxane.100"
ocH3
o rn'.-"urs
(
l l
Y"ur,
1
I
Y"coHs
ocH3
ocH3
2 (21o/o) 140"
|
I
* (
o r--\.-.c6+s
3 I I
stabfe isomer 3. Optimal yields of 3 (5570) are obtained in refluxing xylene (140') in the presence of triarylphosphines.Terminal alkynes do not undergo this reac-
.:
o
o
l3
o + CH3O
,,:"'X*(to)u -
bcH.
"u"u-"r. - (Y""" \,^-cH.
YcH.
majorproduct
minor product
ocH3
)lc\ I with Danishefsky'sdiene (L.5 :,. 2 in 62Vayield.
. (\"""' ocH3
tion, but unsymmetricalalkynes react with some selectivity (equationI). The complex of a substitutedcyclopropanereactswith high regioselectivity(equationII).
Thngstencarbenecomplexes
- i
C"Ho
(ll)
B-1 t,'
w(co), '\--lo \
CoHs coHs-----coHs -
ocH3
CoHs 'CoHs
Note that the cyclopropyl chromium carbene corresponding to I reacts with acetylenes to form cyclopentenones with loss of ethylene (f4,93). I B. A. Anderson,W. D. Wulff, T. S. Powers,S. Tribbitt, and A. L. Rheingold,Am. Soc., ll4, 10784 (1992). 2J. Bao, V. Dragisich,S. Wenglowsky, and W.D. Wulff, ibid., f f3,9873 (1991). 3 J . W . H e r n d o n ,G . C h a t t e r j e eP, . P . P a t e l ,J . J . M a t a s i ,S . U . T u m e r , J . J . H a r p s ,a n d M . D . R e i d ,
Urea-Hyd Pero4 merciallv a it can be p H2O2 coml
cl
ibid., tt3, 7808 (1991).
I R . B a l l i n r .l
'CoHs .
C6H5
ocH3 ' , \ : : i tJ c c t v l e n e s
Urea-Hydrogen peroxide complex, H2NCONH2' HzOz. Peroxytrifluoroacetic acid, CF3COOOH.\ This peracetic acid is no longer commercialfy availablesince9OVaH2O2is requiredfor the oxidationof CF3COOH.However, it can be preparedin the laboratory by oxidation of trifluoroaceticanhydride with the H2O2 complex with urea.
, , . : \ , I .D . R e i d ,
cH3(cHd4cH=NoH
6)
cF3coooH
r'roH 60%
CHg(CHz)qCHzNOz
c6HscH2N02
I R. Ballini, E. Marcantoni,and M. Petrini, TetrahedronLetters, 33, 4835 (1992).
9-Vinyl-9-borabicyclo[3.3.l]nonane (vinyl-9-BBN). This reagentis preparedby reactionof B-bromo-9-BBN with vinyltributyltin:
B,.-o
cH2^snBu,
cH2ct2
cHr?-B,.}'
Otheri4 trans- and cis< ately reactivcd Mnyldimerh.,been preparedI of thesevinvlh but shows lo*r and afford bcn regioselectiveo All the vinvlbo
74/"
1, b.p.28-30"/0.25 mm
CHr-
Diels-Alder reactions.t 9-vinyl-9-BBN is a more reactivedienophilethan methyl acrylate, and undergoesDiels-Alder reactionsat 25-55". Although the reaction with isoprenesshows the expected"para" selectivity, the reaction with lrans-piperylene shows an unusual"meta"-selectivity,possiblyas a result ofsteric factors.This reactionalso can show high endo-stereoselectivity (92:8).
,,"("" * , 7sv"
cHr^cH,
(""
cur"\J
+
1
25" 71"/"
CHs
rf^yto-
"t.)a)-tO
..--..--tO
l l l \ / z
Y
cHe
\-/
e3:7
+
92:8
(endo)
raY'o
lD.A. Singlerm 2 D. A. Singleroo
VinyldichloroD Diels-AI&t at 110"lo formi (equationl). Of
\.-
cHs (exo)
"t'Y" (r) cH.Act
a"^' + 1ss. _ ; ;f-..-ato
0
#
r---ato
**o#
CHr'-(Ct (il)
|
cH.Act
VinYldichloroborane 403 othervinylboranes.2onedisadvantageofvinyl-g.BBNistheconversion^t25"to trans-andcls-dimers.ThisreactioncanIimityieldsinDiels_Alderreactionswithmoder(2)' by use of 1-vinyl-3,6-dimethylborepane ately reactivedienes.This problem is solved (4) has best generatedin situ'Trivinylborane Vinyldimethylborane (3) is pyrophoric and is reactive most is the with BBr3. Trivinylborane beenpreparedby reactionoiulnyrtutyrtin ofthesevinylboranes.vinyldimethylborepane(2)isthemoststableofthevinylboranes' butshowslowerreactivitywithdienes;however'thereactionsaresignificantlycleaner of the absenceof dimerization' The most and afford better yields, probably because probably owing to steric hindrance' regioselectiveof theseboranes1-4 is vinyl-9-BBN, the highest selectivity shown by 2' All the vinylboranes are endo-selective'with
cH,-r/-lacH' |
s!:
("",
, i ' -
.i '
B(CH=CH2)3
CHz:C119,"".,, 3
\B/ lk:-.
4
2
! r . : -
I D.A. SingletonandJ.P. Martinez,Am' Soc''ll2' 7423(1990\' (1992). 2D'A. Singleton' J.V. watson'andG.M. Ndip,Terrahedron,48,5831 J.P.Martrrre.z,
t ,
Vinyldichloroborane. Diels-Alderreactions.|Mnyldichloroboranereactswithsimpledienesintoluene are isolatedas the boronic estersofpinacol at 110. to form adductsin good yield. These bond of the adduct can be replaced by (equationI). Of greater inlerest, the C-B
t1r"r. CH|'?,CH2 (l)
|
cH.
(-
BCt2 1 ) C 6 H 5 C H 3 , 1 1 0 '
+ CH"
cH,
CHs\r,-\.-B-d:
2) HOC(CH3)2c(cH3)20H
ca{v
?1