Fieser And Fieser's Reagents for Organic Synthesis (Volume 14)

C Ane.

Fieserand Fieser's

Reagentsfor OrganicSynthesis VOLUME FOURTEEN

Mary Fieser Harvard University

@ WILEY

A Wrr-By-INrERscrrNcspuelrcATroN JOHN WILEY & SONS NPw Yonr o CHrcnpsrsR o BRlsneNr TonoNro o SrNcepoRe

frn-f sIF.L {;lt- ''

eL8* V. ,t4

PI

Th lan €fi

361 Prq Xcrt

Lrn Son \ra G

ond \lan cG]

Vortl

CopyrighrO 1989by JohnWiley & Sons,Inc. publishedsimultaneously All rightsreserved. in Canada. Reproductionor translationof any part of this work beyondthat permittedby Section107or l0g of the 1976United.srates CopyrightAct withoutthe permissron ol the copyrightowneris unlawful.Requests for permissionor further informationshouldbe addressed to the Permissions Department,JohnWiley & Sons,Inc. ISBN 0-471-50400-9 ISSN0271-616x Printedin the UnitedStatesof America 1 0 9 8 7 6 5 4 3 2 1

PREFACE This volume reviewssyntheticuse of reagentsreported for the most part from January,1986to August, 1988.The manuscripthas benefitedmarkedlyfrom the carefulscrutinyof John O. Link and Greg Fu, who caughtmany errorsand suggestedmany improvements in the presentations. My co-workersprovidedexpert proofreadingof both galleysand pageproofs.They includePhilip A. Carpino, Keith DeVries,JamesR. Gage,Guy V. Lamoureux.KristinM. Lundy. John K. Lynch,SeiichiP. T. Matsuda,JohnA. Porco,Jr., JohnA. Ragan.Greg Reichard, SorooshShambayati,Robert F. Standaert,EdwardM. Suh, Scott Virgil, Keith Woerpel. Greg Fu supervisedthe proofreadingand providedthe structuralformula based on the x-raydatafor the new Sharpless catalyticreagentfor osmylation of alkenes. Martita F. Barsottiis the photographerfor the pictureof sontepresentand former co-workersfor Reagents. MARY FIESER March 15, 1989

CONTENTS

Reagents t Author index 353 Subjectindex 369

p-Acetamidobenzenesulfonyl azide,p-AcNHCoH.SOrN.(1, m. p. l0g. dec.). The azideis preparedby reactionof the sulfonylchloridewith NaN. in aqueouscHrclr in the presenceof (CrH.)rNClas phase-transfer catalyst. Diazo transfer. This azideis recommendedas a relativelysafesubstitutefor tosyl azidefor diazo-transferreactionsto reactivemethylenegroups.Either DBU or N(CrH.). is a suitablebase.It is also suitablefor synthesisof vinyl diazo compounds.'

c2H5o2ccH2cH:cHCoocr", #

a,",o,"L":cHCooC,H.

' J . S . B a u m ,D . A . S h o o k ,H . M . L . ( le87).

Aceto(carbonyl)cyclopentadienyl(triphenylphosphine)iron (l), lZ, l_2. Reactionsof thispseudooctahedral complexhavebeenstudiedin particulardetail by the Davies group at oxford and the Liebeskindgroup in the united states becauseof its potential use as a chiral auxiliary for control of the absolute stereochemistry of variousreactionsof the acyl enolate.Both R-( )-r and s-( + )I are now availablecommerciaily(Fluka),but at a prohibitivecost ($125.60 per gram). u,p-unsaturated iron acyls.t The aldolsformed by reactionof an aldehyde with the enolateof I canbe dehydrated via the acetateto (E)-a,B-unsaturated iron: acyls(2). Theseproductsundergol,4-additionwith RLi or RNHLi, and the intermediateenolatecan be alkylatedwith high diastereoselectiviry. Thus addition

fnfl

oc-Fe-ccH3 P(C6H5)3 I

,)ts,,NHL, il:!t* fn I t#* oc-Fe-dcH:cHCH,a#I

P(C6H5)3 (E)-2

fnflf"

oc-fe-c-cH P(C6HJ3

3 (24:1)

CHCH,' |

NHBzI

'*\1o B"

,

18%

""/-*\",, cis-4

Acetyl hypofluorite

of BzlNHLi to 2 followedby alkylationwith cHlI gives3 (24: 1), whichon oxidative lactam4' cleavageprovidesthe cls-2,3-disubstituted Asymmetricalkylation.z Deprotonation of ( )-1 provides exclusivelyan (E)-enolate,which is alkylatedto provide a singlediastereomericproduct. Deof waterprovidesthe by oxidation[Brr, Ir, Ce(IV)] in the presence complexation has been usedfor sequence This correspondingacid with the sameconfiguration. acylgroupin ofthe liberation ofthe drug (-)-captopril (3). In this case synthesis the presenceof the amineprovidesthe amide2. (c^H.),P ':'

l, BuL, C ^t \ - . " 2 rB / r s c H . B r

---;(R)-(-)-r

r S .R

$Acl B, bicyc

Is.s

lectir m (2. n

C H "' S B z l I

. /Pr\tc* - "J CP, A I

r)Br,

13sal /

\

l2)\*Acooa,r I r l

\

/ \

CH'SBzl

t "

crc Na/c,H.oH --;;-

,*-"'^an. Y l l : o

e HrSH \

/

I

\ Y,t>r^.r, t l i

o

COOH

COOBzI

I L. S. Liebeskind.M. E. Welkerand R. W. Tengl.Am. Soc'.f08.632tt(1986) r S . G . D a v i e sP . u r eA p p l . C h e m . , f f i , 1 3( 1 9 8 8 ) .

Acetyl hypofluorite,AcOF (1), 12,3-4. Oxygenationof pyridines.t Reactionof the reagentwith pyridineor 4-methin high yield. A similarreactionwith 3ylpyridineresultsin a 2-acetoxypyridine

?"'

#*Ac'F*lfr.

,r,J(\ lsea \^Aoo.

f", Hlo.50",1(\ '(nqa .N^o

whichis givesa l:l mixtureof 2- and 5-acetoxy-3-methylpyridine, methylpyridine of chlorineat the cr-popyridones.Substitution hydrolyzedto the corresponding s i t i o no r e v e n t tsh i so x i d a t i o n '

eth;

liek redu thc I Thc (-) ugn 1

Prc{ thc tidr

3-Acylthiazolidin-2-thiones,chiral ' S . R o z e n , D . H e b e l , a n d D . Z a m i r , A m . S o c . , l ( D , 3 7 8 9( 1 9 8 7 ) . ln B.

3-Acylthiazolidin-2-thiones, chiral, 11, 518-519;12, 4. Bicyclic alkaloids. Nagaoet al.t havedevelopeda generalsynthesisof chiral bicyclicalkaloidswith a nitrogenatom at the ring juncture, suchas pyrrolizidines [6.5], basedon a highlydiastereose[5.5], quinolizidines [6.61,and indolizidines (1' lective alkylationof 3-S

o I l) I 2) Rilcy

Ni

+

H:. Pd/c R

BzIOCHTOCH, 3

| | 4

%

| | I

I

ou".uuHOCH2"-\,," (S)-(-)-4 (93voee)

32

(R)-and(S)-l,l'-BinsPhthyh2'2''diamine

1-Benzyl-(3S)-p-tolylsulfinyl'1'4'dihydropyridine. bromide This chiralNADH modelis preparedby reactionof 3-pyridylmagnesium (11, 312)to give the sulfoxide2, which is a prewith menthyl (S)-p-tolylsulfinate cursorto l.

o

I

lii:ft 1?llll"

Af\,H, t t \*/

l

\C,H,,

cH2c6H5 I, oo * 80o

trci

dra

Asymmetricreductionof ketones. Pioneeringwork by Ohno et al' (6, 36;7 , is a usefulNADH model that 1-benzyl-1,4-dihydronicotinamide 15)hasestablished obtainswith chiral for reductionof carbonylgroups,but only low enantioselectivity dederivativesof this NADH model. In contrast,this chiral 1,4-dihydropyridine rivative(1) reducesq-keto estersin the presenceof Mg(II) or Zn(II) saltsin >9070 of L resultsfrom the beneficialeffect ee (equationI).rThis high stereoselectivity

rR

H.loH

? (l) c.H,dcoocH,

jj:s

c6H-coocHl

* Mg(ClOo),774o 4 Zn(Clo.), 437o

93'91o ee 96voee

of a chiral center adjacentto the Coreactioncenterand from the similarity of a group' sulfinylgroup to a carboxamidegroup as an electron-withdrawing (1988). r T. Imanishi, andc. Iwata,J. C. S. Chem.Comm.,473 H. Yoshikawa, Y. Hamano, (1). (R)-(+)- and (S)-(- )-1,1''Binaphthyl'2,2"diamine with hydrazineat L60oand is RacemicI is preparedby reactionof 2-naphthol

Z\a\oH I

\-r\z

ll

|

-

N4NH,.,80"

604s%

NHt NH,

H form unc!

(R)- and (S)-1,1'-Binaphthyl-2,2'-diamine

omide a pre-

33

NH, NH,

(R)-(+)-r

(s){-lt

resolvedwith d-lO-camphorsulfonic acid, which forms a 1 : 1 salt with (R)-( + )-1.1 Asymmetriclactonization2 The diamide3, preparedfrom (R)-1 and 2, on treatment with TFA is convertedinto the 8-lactone4 in 98Vode by a highly diastereoselective reactionwith the pro-S-carbonylgroup of 3. :, . -1h7 lmodel h chiral Jrnedet '90Vo

O

O

ll

A

I

c

O

ll

llll,',"'u (R)-(+)-l + ctc(cHr)3c(cHr)3eclL)wn , 2

al cffect

o Hll

NC-(CH2)3\ NC-(CH").-

;cHoH

cFlcooH, cHrclr, -20.. qumt

Hll o Int\ of a

3 -.r 1988). r

{r' lnd is

NH,

l) Ac?O,py 2) LiBH. 3) TSOH

H

(cHr)4oH .H

NC-(CH.).

Hll o

4 gSVo de\

O

O 5 (98Vo ee)

However,similarcyclizationof the relateddiamide6 resultsin the 1-lactonez, formed with moderatediastereoselectivity with the pro-R carbonyl group. The unexpectedasymmetricbias is ascribedto the highly straineddiamidering of 6.

1,1'-Binaphthyh2,2"dicarboxylicecid

Bhcr I

NH. dona remq unde In or D€sih

o o

ol..

$t-,.",,,{,2 NHt

de) 7 (71Vo J' Org''50'4345(1985)' I K. J. Brown,M. S. Berry,andJ' R' Murdoch' Soc''109'7188(1987)' Am' 2A. Sakamoto, Oda' J and Y. Yamamoto, acid (1)' (RS)-l can be resolvedwith brucine' 1,1'-Binaphthyl'2,2"dicarboxylic in acetone' which selectivelyforms a salt with (R)-1 that is insoluble (S)- or (R)-1 can be Resolutionof a'alkylbenzyl alcohols,C6H'CH(OH)R' with one complexes of used to resolvealcoholssuch as 2 by selectiveformation (R)-enantiomer the with enantiomer.Thus (S)-l' selectivelyforms a 2:1 complex

OH

I

I

Ys(( rP W

Brs(l Ct effectc cl:Pdll by rhir toleral IJ alkyny provrdr t oa ( Z or(2.2 of thc I

cH!(cfi

C6H5CHR 2a = C2Hs,707oee (R) 907o ee (R) b = Pr,

(s)-1 givesfree (R)-2 in of 2, which on decompositionwith aqueousNaOH group' bulky a However,clathratesare not formed when R is

'10-90Voee'

lS. Kanoh,Y. Hongoh,S. Katoh,M. Motoi,andH. Suda,J. C. s. Chem.Comm',405 (l988).

Cq lvzes | moallgi of wata

Bis(acetonihile)dichloropattadium(II)

35

Birch reduction. Regioselectivecontrol.r The site of reduction of a polynuclear arene by Lil NH. can be controlled by the presenceof an electron-withdrawing or electrondonatinggroup. A trimethylsilylgroupis usefulfor this purpose,sinceit is readily removableand is a strongactivatinggroup.Thus2-methoxynaphthalene is reduced underBirch conditionsto 2-methoxy-3,4-dihydronapthalene as the major product. In contrast,the silylatedderivativeI is reducedin the silylatedring to provide2. Desilylationof 2 gives2-methoxy-5,8-dihydronaphthalene (3).

o

d

Z

r','\,OCH3

I

ll

|

V\2 t

Li, *",, /,,\,,\,OCH3 -l 7'%ll ll

s(cH3)3 I

\/\2

Bu.r.{F ,

ocH3

'"l#.

t

s(cHJ3 ,

lP. W. Rabideau andG. L. Karrick,Tetrahedron (1,ggT. Letters,?A,Z4Sl

t ructne,

- l c . r nb e * rth one |:tntlomer

Bis(acetonitrile)dichloropalladium(II). coupling of vinyl halides with vinyltin reagents.t This cross-couplingcan be effectedat room temperaturein DMF in the presenceof (cH,cN)rpdcl, or CI,Pd[P(C6H5).1,. Pure(E,E)-, (E,Z)-, (Z,E)-,or (Z,Z)-1,3dienescanbe prepared by this reaction, since the geometry of each partner is retained. The reaction toleratesmany functionalgroups. |,3'Enynes. In the presenceof this pd(II) catalyst,vinyl iodidescouplewith alkynyltrimethylstannanes with retentionof the geometryof the vinyl iodide to provide1,3-enynes in high yields.2Sincethe conjugatedtriple bond can be reduced to a (Z)-doublebond stereospecifically, the couplingalsoprovidesa route to (z,E)or (z,z)-1,3-dienes. An exampleis thesynthesis of bombykol(l), the sexattractant of the silkworm moth. CHr(CHr)rC- CSn(CHr),+ 1,,.2-

CHr(CHr)rC-C-,7

gr.ryg 97Vo de')

Yi funct

,P.A Tard :K.TE

Bn(ctl Scl used in cluding or q'clo of sccq retentb is not q

Pc.r

: l'. lshu. ilQi6,:'

Bis(cyclopentadienyl)dihydridozirconium

N(COD),.P(qH,)3,IBSO

/

\ . uL

I r2

1 I

t'c pretnceof reactlon

Theseexamples(andothers)indicatethailrans-fusedproductsarefavoredwhen the two dienesare joined by a four-carbonchain, whereascr,s-fused productsare favoredby connectionwith a three-carbonchain.The first examplealsoshowsthat high stereoinductionis possiblein this intramolecularreaction. Cyclization of enyneswith isocyanides.2 In the presenceof Ni(COD), (l equiv.) complexedwith PBu,, 1,6-enynes and an isocyanidecyclizeto l-imino-2cyclopentenes, which can be hydrolyzedto cyclopentenones. Example:

Pr \

d--=-* .'4cH,

R = C6H5 R=Bu

*

ArNC

N(COD)2, DMF,

*'

92Vo 471o

,

2:l J: I

Yields are lower in cyclizationswith FBuNC and in the absenceof an oxygen function betweenthe two unsaturatedbonds. r P . A . W e n d e r a n d Nl.hCl e . ,Am.Soc.,l0E,4678(1986);p.A.WenderandM.L.Snapper. Tetrahedron Letters,23,2221( 1987\. r K. Tamao,K. Kobayashi, andY. Ito, Am. Soc..fl0, 1286(1988). ettciently ncmbered

Bis(cyclopentadienyl)dihydridozirconium, CprZrH, (1). preparation.r Selective oxidation of allylic alcohols.2 This zircononcenecomplex when usedin catalyticamount can effectan oppenauer-typeoxidationof alcohols,includingallylic ones,in the presenceof a hydrogenacceptor,usuallybenzaldehyde or cyclohexanone. This systemoxidizesprimaryalcoholsselectivelyin the presence of secondaryones. Thus primary allylic alcoholsare oxidizedto the enals with retentionof the configurationof the double bond in 75-95voyield. The method is not usefulfor oxidationof propargylicalcohols. I P.C. WailesandH. Weigold, J. Organometal. Chem.,A, 405(191.0). r Y. Ishii,T. Nakano, A. Inada,Y. Kishigami, K. Sakurai, andM. Ogawa,J. Org.,Sl,240 (1986); T. Nakano, Y. Ishii,andM. Ogawa, (1987). ibid.,52,4855

3E

(R)-and(S)-2,2"Bis(diphenylphosphino)'1'l"binaphthvl

Pd(dba)'' Bis(dibenzylideneacetone)palladium(0)' (4) in a synthesisof (E)-neomanoalide step The key Stille coupling(rz' #i'' involvespalladium-catalyzedcouplingofanallylhalidewithana.stannylfuran' P(CuHr)rto form 3 as a 1:1 Thus 1 and 2 couplein ih" p."r"n." of eolauu;, and of 3 to 4 involves Conversion yield' mixture of (E)- and (Z)-isomers in 66Vo a 2-silylfuranto a of oxidation oxygen reduction(DIBAH) and selectivesinglet butenolide. eu.Sn.-azolr,S i(CH3)3

+

\// HOHrC/-

, r,""",,. uoo"ro,oou,, f

I

l19l (1987)' Leuers'2iE' rS. Katsumura, andS' Isoe'Tetrahedron S. Fuliwara, (BINAP)' Supplier: (R)- and (S)'2,2"Bis(diphenylphosphino)'1,1'-binaphthyl Fluka. complexesof Enantioselectivecatalytic hydrogenation' The ruthenium(Il) hydrogenation asymmetric catalyze ligand, (R)- and (S)-1,bearinga chiral BINAP to give (1R)- or (1S)-tetrahydroisoof N-acyl-1-alkylidenetetrahydroisoquinolines (2)' preparedby acylationof gS-tOOEo (Z)-enamide ee.r Thus the quinolinesin of (R)'1 to (iR)presence the in 3.4-dihydropapaverine,is hydrogenated on use of (S)-1 (1S)-3 is obtained (3). The enantiomeric tetrahydroisoquinolines as catalyst. Awiderangeofa,p-unsaturatedcarboxylicacids,includingsubstitutedacrylic homogeneoushydrogenationwhen catalyzedby acids,undergoenantioselective

i ( (

(R)- and (SF2,2'-Bis(diphenylphosphino)-1,1'-binephlhyl

de (4) furan. ,a1:1 t\ rtlves

(R)-l

(s)_t

Ph, o

H ,r ,

/cHt

,>+"
T -I

Ph, 9:

-o

Ph, o-

tcH,,

'CH.

CH,O)ZY^)

cH30

,*, #.r,oV--?,ftcocH'

cH3o

lll,t

ocH3

ocH3

ocH3

OCH?

(z)-2

(1R)-3(>99.57o ee)

the BINAP ligand,suchas (R)- and (S)-1.' ruthenium(Il) carboxylatespossessing Chemicalyields are nearly quantitative;optical yields dependupon the doublebond geometryand the substitutionpattern,but opticalyieldsof greaterthan90% can be obtained by suitablechangeof hydrogenpressure.This systemcan also effect selectivehydrogenationof only the c,B-double bond. The reaction also providesa route to optically active hydroxy acidsor the correspondinglactones. A few p,1-unsaturatedacidscan be hydrogenatedenantioselectively. hydrogenationof proRu(II)-BINAP complexes(1) can effectenantioselective of other doublebonds chiralallylicandhomoallylicalcohols,withouthydrogenation in the samesubstrate.rThe alcoholsgeraniol(2) and nerol (3) can be reducedto either (R)- or (S)-citronellol(4) by choiceof either (R)- or (S)-1. Thus the stereochemicaloutcomedependson the geometryof the doublebond and the chirality CH,

Supplier: nplexesof :osenation ahrdroisorlation of ro (1R)se of (S)-1

t cHw

CH,

-

l

(s)-1, g11 H'' ""

.,

f",

ffo"

f', (R)-4

\

/ H" (R)-r

/

\ H,.(s)-l ) CH.

(s)-4 rted acrYlic rtalvzedbY

40

(R)-nnd(S)-2,2'-Bis(diphenylphosphino).1,1'-binrphthyl

of the catalyst.In either casethe optical yields are 96-99% ee. Homogeraniolis hydrogenatedwith (S)-1in the samesenseas2 and in 92Voee,but in this casethe isolateddouble bond is also reduced. Somewhatmore effectivecatalystsare obtained by replacingBINAP with ToIBINAP, which is 2,2'-bis(di-p-tolylphosphino)-1,1'-binaphthyl.a The presently preferredcatalystsare complexesof Ru(OCOCFT),with (R)- or (S)-ToIBINAP, obtainedby treatmentof Ru(OAc)r.ToIBINAPwith 2 equiv.of trifluoroaceticacid. Such catafystspromote hydrogenationof typical enamidesin 98Voee and 98Vo yield. This reactioncan be used to provide asymmetricsynthesisof isoquinoline alkaloidsas well as of morphinansusedas substitutesfor morphine. Asymmetric hydrogenation of prochiral ketones.s Ketones substitutedin the cr- or B-positionby diversepolar groups,particularlyOH,OR,NRT,COOR, can undergo highly enantioselectivehydrogenationcatalyzedby BINAP-Ru complexes.A key factor of asymmetricinductionis undoubtedlychelationof the carbonyl group and the heteroatom to the Ru atom. Examples:

gH

H2,

?

cH^/N(cHJ, +P

l5: oIa oIa

dior tcro l-pa

ggz\_,N(CH,), (96Vo ee)

OH

O O H l r " . nu-G)-r ll I

l*.-

CHY

(R sil hx

(D

OH

t

t

CHV (987o ee)

Enantioselectivity is generallyreducedby the presenceof two functionalgroups, probably becauseof competitiveligation; generally,the effectof an ester group overridesthat of an alkoxyl or siloxylgroup. Two-stepasymmetrichydrogenationof p-diketonesshowsthat the overallstereochemistryis determinedby the catalystand by the chirality of the intermediate hydroxyketone.Thus partial hydrogenationof acetylacetone (2) catalyzedby RuO O H ll ll CHi\,ACH,,

-

. . nu-dir.r

O

H

O

H

R":a)r R,R-4+ meso-4 ee:l

i li cHV\cH,

t

3 (98.59oee) I tt' nu-(s)-r J I O H

cH, R,R-4

t,

t

O

l

cH!\cH,

15:85

meso-4

H

tltl

ee. b 99A nedrc Evidl €tal! A plexe on tn formr drogc estcrs

(R)-and(S)-2,2'-Bis(diphenylphosphino)-1'1'-binaphthyl4l I l:

he

(R)-1 resultsin the (R)-hydroxy ketone (3) as expected.Further hydrogenation with the same catalystgives R,R-4 and meso-4in the ratio 99:1' In contrast, hydrogenationof 3 catalyzedby Ru-(S)-l givesthe samediols, but in the ratio

irh rtl\ \P. rd 8.; ine the can )m-

o

o

\__/

Hz

-Ru-(s)-l lffiVa

CH,

CH,

5

15:85.Hydrogenationof diacetyl(5) catalyzedby (S)-f-Ru givesa 74:26 mixture of meso-6and S,5-6.Evidentlyin this reductioncatalystcontrolfavoringformation of meso-diolsdominatesover substratecontrol favoringformation of / or d-diols. hydrogenationoflrS'diketones.6 Hydrogenationof 1,3-alkaneStereoselective dionescatalyzedby Ru,Cl[(R)-1][N(CrH,).]resultsin anti'|,3-diolswith high dias(equationI). Under the sameconditions tereoisomericand enantiomericexcesses (2) is reducedmainly to the p-hydroxyketone3 in 98Vo l-phenyl-1,3-butanedione

(l)

to' 'CH,-.A/R

CH,>A/R

l

O

6

l

l

O

R = CH3 R = r-Bu

H

l

O

+ CH3V/\,R

:

H

)999o ee 98% ee

98% 8470

O

l

H

:

:

O

H

99:7 9l:.9

Ru-(R)-r

)ups. roup

1ll)

4

CHr\fr\-CeHs

8

8

o

+ CHiv,'\/,C6H5

CH,--.2\C6H5

H

8

e

2

:

3 (987o ee) \(gr -

dlate

2

o

H

6

anti-4

_j*#L

Ru-

.{

ee, but under more drasticconditionsit also is reducedtothe anti-|,3 diol (4) in 99Voee. Alkanonesare not reducedunder the mild conditionsusedfor the alkanediones,and hydrogenationof I,2- and 1,4-diketonesgive complex mixtures. with the ruthenium Evidentlyhydrogenationis facilitatedby chelationof 1,3-diones catalyst. Asymmetric hydrogenation of p'keto esterc.1 The Ru(OAc)2(BINAP) complexesare ineffectivecatalystsfor asymmetrichydrogenationof p-keto esters,but on treatmentwith HX (2 equiv.) are convertedinto complexeswith the empirical hyformula RuXz(BINAP), which are effectivecatalystsfor this enantioselective drogenation.Complexesof (R)-BINAP catalyzehydrogenationto (R)-B-hydroxy estersin >99Vo ee, whereasthe enantiomeric(S)-p-hydroxyestersare obtained

"

42

(R)-rnd(S)'2'2"Bis(diphenylphosphino)'1'1'-binaphthyl

The enanby use of complexesof (S)-BINAP in equally high enantioselectivity. tioselectivityis independentof the natureof the estergroup or of the chainlength. The RuzClo(BINAP)r[N(CrH5)lcomplex (13, 36-37) is equally effectivefor this hydrogenation. enantioselective (l) catalyzedby Catalytic hydrogenationof ethyl c-methyl-p-oxobutanoate RuBr,[(R)-BINAP] gives a 1: L mixture to two B-hydroxyesters,both of which havethe (3R)-configuration(equationI).

(r)

o tl

Hz, RuBrrl(R)-BINAP]

611\.'cooczHs " l CH,

OH

OH

t

t

(t)-r

CHA/Cooc2H5 : CH,

+ CHA/Cooc2H5 I

2 (49Vo,97Voee)

CH,

3 (Sl%o,969oee)

Asymmetric isomeriZationt Cationic Rh-phosphinecomplexessuch as I can effectisomerizationof allylic substratesby a 1,3-hydrogenmigration(12,56-57). C.H.

f,"rtutt' )nnlHocu,1,

clqp/ \-cutt, CuHt

(R)-1 (2) resultsin 1,3-cyclopenSuchan isomerizationof 4-hydroxy-2-cyclopentenone tanedione(3) via the keto enol. On exposureof racemic2 to the optically active Rh-BINAP complex(R)-1, the (S)-enantiomerisomerizesmore rapidly than (R)2 to give, after 14 daysat 0', a mixture of 3 and (R)-2 in 9lVo ee.

o

o /

t

t

OH ,

nl

E)-1, THF,O"

+

\

\-.lJ OH (R)-2,274o (919oee)

q eff c{I

ofl obl

(R)- end (S)-2,2'-Bb(diphenylphosphino)-1'1'-binephthyl

I enanl en g t h . br this zcd bY ' rrhich

Kinetic resolution of altylic alcohols,e The (R)- and (S)-BINAP-Ru diacetate complexescan resolveracemicallylic alcohols,both acyclicand cyclic,with high enantiomeric selectivity. Thus hydrogenationof (-t-)-2 catalyzedby (S)-1 at 767o conversionprovides(S)-2 (>99Eoee) and anti-3 (49:I,39Vo ee). Hydrogenation of (S)-2 catalyzedby either (R)- or (S)-l providesanti-! (>23:1). Similar results obtain with (t)-4. OH I gH ' l t/coocH' l CH, (t)-2

OH

OH

I + cHlcoocH3 :

d'."-6coocH3

CHt

CH,

(s)-2 l tt'' (R)-

ooc2H5

|

(2R,3R)-3(49:l)

ot (s)-1

QH

cH^.cooH l CH,

a: I can it -57).

(2S,3S)-3 ()23:r)

OH

OH

I

tt,

-

-

I

ll rl

R!r' I

^

\,ACH3

\

+

t

...CH,

cH3 (s)-4 I t*t JtL' QH

(t)-4

\ clopenlr active han(R)-

43

l

\Acu,

(rR,3R)-s (959o ee)

4

l1,4-Bis(diphenylphosphine)brtrnelnorbornadienerhodiurn

7 R. Noyori, T. Ohkuma, M. Kitamura, H. Takaya, N. Sayo, H. Kumobayashi,and S Akutagawa,Am. Soc.,10!r,5856(1987).

EM. Kitamura, (1987). Letters,8,4719 R. Noyori,andH. Takaya.Tetahedron K. Manabe, e M. Kitamura, J. Org.,53,708(1988). R. Noyori,andH. Takaya, K. Manabe, I. Kasahara, trifluoromethanesul[1r4-Bis(diphenylphosphine)butane]norbornadienerhodium tetrafluoroborate prepare than the (l), to salt is easier 12,426.The triflate fonate usedearlier.

alt A|l

:,I ">-

C.H. l"t-CuH,

"orf

j-a.", CuHt

1 hydrogenation of p-hydroxy acrylates.t These esterscan be Stereoselective catalyzedby DABCO. preparedby condensation of methylacrylatewith aldehydes On hydrogenationcatalyzedby L, theseestersare convertedwith high selectivity esters(equationI). Similar directedhydrogenation into anti-q-methyl-p-hydroxy

Dq

9n, (r) cH,o,ccH:cH2 + c2H5cHo +F

cH3o'c\c'H' OH ) 89% | Hr, I, CH]OH

CH.

I cH,orcl-\zc'Ht : OH 3 (anti, 99Vo)

(.)

co

inl obtainswhen the hydroxyl group is replacedby anotherpolar group: COOCHI, CONR,, NHCOR. The relatedchiral rhodium catalyst4 hasbeenusedto effectkinetic resolution In this catalystthe achiralphosphineligandof I is replaced of thesesubstrates.2 (DIPAMP). Hydrogenationcatby (R,R)-1,2-bis(o-anisylphenylphosphino)ethane

tlYl

't.

:r,

(l! 'J.

45

[1,t]-Bis(diphenylphocphine)butone]norbornodienerhodium

r. :nd S.

....r)CeHs o-CHrOCuHo

1'\

u , 1987). F r1988).

I )rutt...'Norbomadiene \o/ BF,cuHr' \cuttoocur-o

lenesul' i(1b()rate

4

alyzed by 4 of the p-hydroxy acrylate2 to 657ocompletionresultsin (S)-(- )-2 and (2R,3R)-(- )-3 in 977oee (equationI I ) .

9H,

QH,

tl

\'n, cH3orc^,/"u"t 0D 2

+ CH"O,ClcoHs

I OH

6H (s)-2

r\ aanbe D\ B C O . . lcctlvlty )s. nation

hydrogenation of 3-substituteditaconate esterc. HydrogenaStereoselective tion of the dimethyl itaconates(5) catalyzedby I resultsin syn-dialkylsuccinates

cH" i

l

cH3ooctcoocH3 4 l.

(2R,3R)-3 (97Vo ee)

cH. l

cu,oocA.f coocH3

R 5, R = CH3, C2H5,C6H5

9H, cHjooc^/CoocH3 R (R,R)-6

R syn-6(250:l) CH'

t '

cH.ooc^/coocH3 l R

(s,s)-6

('(x)cH.,

(6). The high diastereoselectivity is attributed to the directing influenceof the group. Incompletehydrogenationof 5 with the chiral catalyst4 results COOCH. (R,R)-6; in formation of further hydrogenationof the unreactedprecursorwith I (S,5)-6. gives can be preparedin >96Voee.1 Thus the two syn-2,3-dialkylsuccinates

rc\()lutlon !( rcplaced n.rllr)ncat-

'J. M. Brown,P.L. Evans, (1987). andA. P.James, Org.Syn.,submitted I J. M. Brown,I. Cutting,P. L. Evans,andP. J. Maddox,Tetrahedron Letters,27,3307 0986). 3J. M. BrownandA. P.James,,l. C. S. Chem.Comm.,l81(1987).

6

(R)' and (S)'3,3"8is(triphenylsilyl)binrphthoFTrimetbyleluminum

Cu(hfa)' (L)' I Bis(hexafluoroacetylacetonate)copper(Il), Ylidesfromfi,CN,.Thisreagentismoreeffectivethanbis(acetylacetonate)The decompounds'2 copper(Il) (5,244) for generationof carbenesfrom diazo The rnild .oapo.i,ion proceedsat a lower temperature,even at room temperature' ylides' such heat-sensitive of preparation the in .oniition, are particularlyuseful tellurium' and as thoseof antimony,bismuth, Example:

; rh ltl

bt

I, CoH.

(c6H5sor)2cN2+ (c6H5)3Sb '181o (c6H5So2)2C:Sb(C6H5)3 I R. L. Belford,A. E. Martell,andM' Calvin"/'Org' Nucl'Chem''2'l1 (1956)' 319(1988)' : C. Glidewell,D. Lloyd,andS' Metcalfe,Synthesis' (R)- and (S)'3,3"Bis(triphenylsilyl)binaphthol-Itimethylrluminum' Thesetworeagentsreacttoformachiralorganoaluminumreagentformulated as (R)- and (S)-1.

t. m

si(c6H5)3

(s)-r AsymmetricDielyAlderreactions.|Diels-Alderreactionsofaldehydeswith compoundcanproceedwith silyloxidienescatalyzedby this chiralorganoaluminum with the silyloxydiene2 at Thus reactionof benzaldehyde hish enantioselectivity.

ct\?

?"",

l, n

l) (R)-1'-20'

2"#' + c6H5cHo

I

CI

(CH3)3sio-

b

CH^,7o

CHt

)

+ CuH, 92:8

l l 3?cuH, : CH, 4

1'2-Bis(/razs-diphenylpynolidino)ethane

n a t e) re dee rnild . such

{l

-20' inthe presenceof l0 mole%oof (R)-f resultsin the clb-dihydropyrone 3 as is dependenton the bulk of the major product in957o ee. The enantioselectivity the triarylsilyl group of 1. Thus replacementof the triphenylsilylgroup of I by groupsincreasesthe enantio-and cls-selectivity, but replacement tris(3,5-xylyl)silyl by trimethylsilylgroupsreducesthe enantioselectivity. C-Glycosides.2Reactionof an aldehydewith the diene 2 catalyzedby (R)-1 resultsin dihydropyrones(3) in 80-97Voee, which can be convertedto the glycals

ocH" "

)

lll'#.,, n

G).,,Ci +RcHo

?o'

nAo/

oAAn

nulated

(5), in which the 4. Theseglycalsreactwith trialkylaluminumsto give C-glycosides trans-isomerpredominates. Example: OAc

I

CH,

al c"ni\o/ 4

dcswith eed with e n e2 a t

cH' cL)

*crs-5 cunfe/""p

AI(CH3)3 Al(d-Bu), (CrH5)rAlC-CBu

96Vo 74Vo 857o

trans-S

96:.4 94:6 100:0

I K. Maruoka,T. I t o h , T . S h i r a s a k a ,a n d H . Y a m a m o t oA, m . S o c . ,f f 0 , 3 1 0 ( 1 9 8 8 ) . r K. Maruoka.K. Nonoshita, T. Itoh, and H Yamamoto, Chem. Letters,2215(1987').

(f). The chiral diamine is prepared'by 1,2-Bis(tans-diphenylpynolidino)ethane reactionof (3R,aR)- or (3S,4S)-diphenylpyrrolidine with oxalyl chloride and triethylaminefollowed by reductionof the resultingdione with lithium aluminum hydride.

'o CuHt'..r1

Aau", t,

,"--.-/CuHt

..",JJ-V..", (3R,4R)-(-)-1,crD- l43o

4E

t,2-Bis(rrarsdiphenylpynolidino)ethane

Asymmetric addition of Grignard reagentsto C6II|CHO.2 Grignard reagents pretreatedwith (-)-1 at -78'add to benzaldehydewith only slight enantioselectivity (-20Vo ee). But if the addition is effectedin the presenceof 2,4,6-tti' ee. dichloride(2), the carbinolis obtainedin 40--70Vo methylphenoxyaluminum

I ' 1

tr

al

.---arCHt / / \

cH,-(

roAlcl,

(2)

.CH" H\."oH

1,2.

cuHfn

* RMgBr# c6H5cHo

(40-707o ee)

Asymmenic osmylation of alkenes.t In the presenceof 1 equiv. each of I Highest crs-dihydroxylation. and OsOo,alkenesundergo highly enantioselective trisuband trans-diof enantiofacialselectivity(90-997o)is shownin osmylation

b! r{

OsO",(*)-l H. | .R' \ ' / / - \ ' nlul

R' ' 1

OsO.,(-)-f A

stitutedalkenes,and the enantiofacedifferentiationis completelycontrolledby the chiral diamine(A). Optical yieldsare only moderatein the caseof cis-alkenes. Examples:

o! (l a

t osq,(-)-r,

C6Hi\.'c"'

--#-------

H.

CHr

cuHrfio..

o1 .j

\

cH3-l-ct CH,

cH:cH,

2 *,,,, q1.A-ot j:-'

.t \ TeEc cHsto CH,

2 (86Vo de)

QH:CH, !

q1cH,+d CH.

(^,

coocH3LDA) q*coocH3 4w'cH3J-ct oH

v

CH,

vinyl group of the rearrangedhomoallylicalcoholis syn to the c-o bond of the original asymmetriccenter. of Il,2l-wittig reafrangemenr. The [1,2lwittig rearrangement B-alkoxyalkyl allyl ethersshowsa high syn-selectivity,althoughthe chemicalyields are low becauseof concomitant1.,4-rearrangement."

o

c o

u

Butvllithium ned bY ; t.rf the I ether.

ffI

Examples:

cH3vcH3

cH3vcH3

oAo (,|-o-.Acs.

,yiff,

32% ?^? \AAo"",

?"

(12:l)

CH, rrorable rates Ltr\t (rhtalns cl\c the

(15:1)

(a-Hydroxyalkyllsilanes.e Thesea-alkoxysilanescanbe preparedby addition (or of Bu.SnLi to an aldehydefollowed by silylation with cyanotrimethylsilane trimethylsilyltriflate). Transmetallation of the adduct(BuLi) resultsin rearrangeos(cH3)3 os(cHJ3l ,)BqsnLi | 2)(cHJ'sicN) 3BuLi'-78o) RcHo RAsnBu" I LnAli so-rs*| wcrrll

I

OH

I

R,

cH.

nd of the k o r ra l k Y l e low be-

silcHrl,

ment of the silyl group from oxygento carbonto give c-alkoxysilanes in 50-65Vo overall yield. This rearrangementis the reverseof the Brook rearrangementof a C-Si bond to an O-Si bond, and is possiblebecauseof the faciletransmetallation of Sn to Li. This rearrangementhas beenappliedto a ketone;in this case,useof trimethylstannyllithium is requiredfor successful rearrangement(equationI).

(D + Q.3,i"",,, G" - l(){i,':;:,],] Ketonehomoenolates.toAddition of BuLi to the potassiumalkoxide(2) of a (1) resultsin partial isomerizationvia a to the corresponding 3-hydroxy-1-alkene

ButyllithiunrTetrrmethylethylenedirmine

6E

(b) is also formed' as 3-alkanone(3). Under usual conditionsthe homoenolate 4' shownby alkYlationto Provide Example: K,

n'1AcH, I

jgn'A..,AcH,9 r _ OK

OH

1, Rr = C6Hr3

l-'+cH,+-'^^l Ko""""Lil or L

'.i*"

n'lfcn, o

(r

alt

x

b

-./ '' lnt,

I tn':GLoLcH(cHJJ

*',,F*' o

str o-l ql

3 I J. Einhorn and J. L. Luche,J. Org',52,4124 (198'7)' ' G . B . P a y n ei,b i d . , n ' 3 8 1 9( 1 9 6 2 ) ' chem' Comm''356(1988)' I P.C. BulmanPage,c. tu. nuyn"r, andI. o. Sutherland'.I.c.s, 761 (1988)' Letters,2g' { w. H. Pearson,D. P. Szura,"andw. G. Harter,Tetrahedron 5 C. A. Broka, w. J. Lee, andT. Shen,J' Org" 53' 1336(1988)' oJ.A.Marshall,T.M.JensenandB'S'DeHofibid"Sl'4316(1986);52'3860(1987); J.A.Marshall,J.Lebreton'B.S'DeHoff,andT'M'Jensen'ibid''52'3883(1987)' 7 R. Briicknerand H. Priepke,Angew'Chem'Int' Ed''n' 278 (1988)' 8 S. L. Schreiberand M. T. Goulei TetrahedronLetters'8,1043 (1987)' ' R. J. Lindermanand A. Ghannam,J' Org',53' 2878(1988)' Letters'n'2587 (1987)' l"T. Cuvigny,M. Julia' t-.:uttien,and C' {olando'Tetrahedron ButyllithiunrTetramethylethylenediamine' "Angular The ortho-metalation of a benzyl alcohol has anthrucyclinonis't Thus the cis-tetralol been used to provide a synthesisof angular benzanthraquinone.

(t

OO'

"o-^acH, ,l BuLi,TMEDA

y ' \ ' c H o l l z r r o ' ' +l n -l % l l

\r^eo

tl

cH,J ,\,.,",,, \r'

r.a

r(

dcl to d d

(2R)-2-t-Butyl-6-methyl-2H,4H -1,3-dioxin4-one

69

CH,

d. as

cH30

o 4

(1) after dilithiation condenseswith the aldehydoamide2 to give, after acid-cat4. alyzedcyclization,the phthalide3, a precursorto the natural anthracyclinone I K. Katsuura (1987\. andV. Snieckus. Can.J. Chem..65.124

)r,cHJJ

R.

sec-Butyllithium. Fries rearrangement.t Rearrangementof phenyl esterswith Lewis acidsreketones.In contrast,reactionof an sultsin a mixture of ortho- and para-phenolic o-bromophenylester with sec-butyllithiumresultsin exclusiveformation of the ortho-phenolicketone by an intramolecularacyl rearrangement.2 Example:

ococ(cH3)3 I l'/\li ). S r

.)s7) i

OH

Ja -BuLi + 76%

Br

coc(cH3)3

F-

I A. H. Blatt, Org. React.,l,342 (1942). ' J . A . M i l l e r ,J . O r 9 . , 5 2 , 3 2 2 ( 1 9 8 7 ) . l:e\-)

h,,l has -tctralol -CH,

)

/ (2R)-2-r-Butyl-6-methyt-2ll,,lll'1,3-dioxin-4-one, ?t

f(cHJ3 -

cHa\

-? l

(l).m.p.48.5",

o

of pivaldehyde uo-217o; Supplier:Fluka.The dioxinoneis preparedby acetalization (R)-3-hydroxybutanoic and hydrodebromination acidfollowedby bromination with (60Voyield).' Stereoselective hydrogenation.2 Catalytic hydrogenationof 1 or of the bromo (>98Vode) with H transfer derivatives(2) occurswith completediastereoselectivity to the face oppositeto that of the t-Bu group to regeneratethe stereogeniccenter of (R)-hydroxybutanoicacid (4). The result is unexpectedbecausethe two faces of the double bond are similar in resoectto sterichindrance.

r-Butyl trichlororcetimidate

E(CH3)3

f(cHJ3 oAo -

f

gAq t

l

BrcHAAO ' l

H.-Pdrc

OH I

gHA'rcooH

*r/Jo - H

4

c*

B(H) , adconiugateaddition' The dioxinone 1 undergoesconjugate Stereoselective group alkyl the which in adduct dition with lithium dialklcuprates to give a single carbon-'cuprate is cri to the /-butyl group, with no reaction occurring at the acetal of the three pyramidalization by additionto the lesshinderedfaceof I is explained trigonalcenters.3 Example:

(lo redr but) ethc J Cr

f(cHJ3 Hcl oAo l+(c6H5)2culi+cul.lAo CuHt

OH I

#.."4-t-" CH, (3R)-2'oD- l0'2"

(1987)' I J. Zimmerman Helv',70,1104 andD. Seebach, ' Y. NodaandD. Seebach' ibid.,70,2137(1987)' Am' Soc''llo' 4763 I D. Seebach, L zimmermani,i-l' cyttr, ir' ziegtet'andT'-K' Ha' (1e88). '.-NH (1)' b'p' 65-69"/12 mm' The ret-Butyl trichloroacetimidate,CLCCA^Ao l OH

v

erythro-3

.r I ctl-

i.lc 2.

Oxidation of p-hydroxy selenides.s p-Hydroxy selenides(t), obtained by reactionof a dialkyl ketone with phenylselenenylmethyllithium, are oxidized by

S5

m'ChloroPerbenzoic ocid

(equation I). The samesequence acid in methanol to epoxides m_chloroperbenzoic This r"*ult' in one-carbonhomologation' when applied ,o un uutyt'u;yl-k;;"*

Rl O -)c:o

oH,€8'", jXt

- 'r"ffff') R\^.oH

'ts-ss%K

Rrlt-CHrs"cuH,

O

I

GI)

C6H5COCH3 -

adduct

clc6H'c0'H ) cH3ccHrc6H j

o ketone fused to a for ring enlargementof a cyclic oxidation providesa method benzenering (equationIII)'

CrHrScCH,Li-

ffiH'SecuH'rr#sfr to triprimll or secondary'are converted Nef reaction.a Nitro compounds' chloride with a trialkylsilyl ti'un S 07oyieldby reaction alkylsilyl nitronatesrn g'"ui"t nitro compounds secondarv from a"riulo and DBU in cH,cl,' il;;i;t;;;nut"t yield' This sequenceis not at 25' to ketonesin high are oxidizedby CIC.HaCO'H nitro compoundsto aldehydes' usefulfor conversionof primary ExamPle:

?"", .."5f*o,

ocH" I

crHry CHt

CH, of cortisone step in a recent total synthesis Corticoid side chain'| The final construction (1) for ether silyl of an enol (2) employeda noveldoubleiyJroxyration KHCO' in 3 equiv' of the peracidand *itt' t oi of the side chain.Thus it*"n"nt at both c'' and C''' ii*irct, "io" resultsin hydroxylation

Chlorotriisopropoxytitanium(l)

CH,

cH20H I

#h*

l H . K o g e na n dT . N i s h i ,L C . S . C h e m .C o m m . , 3 1 1( 1 9 8 7 ) . : C. W. Jeffordand Y. Wang,ibid.,1513 (1987). r S. Uemura,K. Ohe, and N. Sugita,rbrd.,111,(1988). { J. M. Aizpurua, M. Oiarbide,and C. Palomo,Tetrahedron Letters,8,5361 (1987). 5 Y. Horiguchi,E. Nakamura,and I. Kuwajima,J.Org.,5l,4323 (1986).

sulfide (1). N-ChlorosuccinimideDimethyl Oxidation ol p-hydroxy ketones,' Reaction of the Corey-Kim reagent with these substrates can result in dimethylsulfonium dicarbonylmethylides in 80-98% yield. These S-ylides are desulfurized to p-diketones by zinc in acetic acid. B-

o H o (

o

I Rr^.

\

Innde rnd: n{)t

'aO

ll

l, cHcrt R';;;;

o o l l t l -dz,tqotc

R'alR' tl

o

o

ll

ll

R,\4n2

s(cHJ2

Hydroxy ketonesthat are mono- or disubstitutedat the ct-positionare oxidized by the reagentin moderateto good yield. directly to 1,3-diketones rS. Katayama, Syntftesrs, 178(1988). K. Fukuda,T. Watanabe, andM. Yamauchi, Chlorotriisopropoxytitanium(1). Aldol-type rcaction of zinc esterc.t This titanium reagentpromotescondencompounds(13, 220) with aldehydesor sation of (ethoxycarbonylalkyl)iodozinc ketonesto provide hydroxy estersand/or lactones.The active reagentmay be (ethoxycarbonyl)alkyltriisopropoxytitanium. Examples:

H. lS{)ne rcllon lO in

j5 IZn(CH2)rCOOC2H5 + C6H5CHO

?H + C6HrC"(CHr)3COOC2H5 (52Vo)

ChlorotrimethylEihne-Phenol

Or cH,-1lcooc2H5 I Znl

s + c6H5cHo;;

venc tnntr intcn been decu

rH. Ochiai.T. Nishihara, Org',53'1343(1988)' andZ. Yoshida,J' Y. Tamaru, triamide' Chlorotrimethylsilane-Hexamethylphosphoric conjugate additions to enalsand enones.t clsi(cH.)./HMPT markedly acceleratesthe Cu(I)-catalyzedconjugateaddition of Grignard reagentsto enals' enones,and unsaturatedesters.The conjugateadditionof organocopperreagents is alsofacilitated. Examples: QzHs

,,*o

CrH. t - -

CH.MgBr.Cul,

RC}

P C lG{

cHrvvosi(cH,)3

HMrr crs(cH,),,

I CH,

H

C*

t

( 9 l o / oE )

reg|o CrHt

cH, tl

CHr.v};.-t I

cH':A.

-'----_ ll

cH, o

seqo

l t cH, osi(cH3)3 (97o/oZ\

Leuers,21 ,4025' r Y. Horiguchi, a, Tetahedron andL Kuwajim E. Nakamura, S.Matsuzawa, 4029(1986). Chlorotrimethylsilane-Phenol. Deprotection ol t-butorycarbonylamino acids.t This reaction is generallyeffected with 507ocF,cooH/cHrclr, with slight, if any, effecton other common protectinggroups.Deprotectioncan alsobe effectedby ClSi(CH')' in combination with phenol, with formation of phenyl trimethylsilyether as the co-product.This cleavageoccursrapidly at room temperaturewith essentiallyno loss of benzyl protectinggroups.Reactionswith ClSi(CH.). alone are markedlyslower' Leuers,T),303 l E. Kaiser,Sr.,J. P.Tam,T. M. Kubiak,andR. B. Merrifield,Tetrahedron ( I e88).

\lrr al\rr alkn ,}r1Kl

TI i{lTx

Chlorotris(triphenylphosphine)cobelt

Chlorotrimethylsilane-Sodiumiodide. Silyl enol ethers.t Aldehydes,ketones,ct,B-enals,and o,p-enonesare converted into the silyl enol ethersin moderateto high yield by reactionwith iodotrimethylsilane,generatedin situ,andN(CrHr).at 25'in acetonitrile.In somecases intermediatestable1,2-or L,4- adductscan be isolated.Thus the 1,2-adducta has beenisolatedas an intermediatein the reactionof some aldehydesand shownto decomposeto the silyl enol ether.

lr acenals. rgents

O S i ( C H . ) .I

[RCH,

lH*a RCH' cHo

L ">(*,.,",,,,

RCH:CHosi(cH3)3 ]-*

rP. Cazeau,F. Duboudin,F. Moulines,O. Babot,andJ. Dunogues,Tetahedron,43,2075, 2089(1987).

Chlorotris(triphenylphosphine)cobalt. Benzoquinones (12, 130).' The maleoyl cobalt complex a shows excellent regioselectivity (about 15-20:l) in thermal reactions (80') with electron-rich al-

Rc-cR'

CH, +

7. .t015,

CH. X

zllr efommon nnation n. This benzyl .19.303

a (X:Cl)

CHi

tr*is acid. 25' -50-10Ec

CHP (R = CH3,Bu, CHzSiRr R' : H, COOC2H',COCH3)

kynes;only marginalregioselectivityis observedin thermal reactionswith other alkynes.However, use of Lewis acid catalysts(SnCl.,,BFr etherate,or AgBFI) allows the reactionto proceedat 25oand can improve the regioselectivityof realkynes. actionswith electron-deficient quinone was used to obtain the isoquinolinequinone2, a unit of This synthesis (equation I). somesaframycinantibiotics

Chlorotris(triphenylphosphine)cobalt

ft ,rz-t.-

I

(I)

l

"*fi : (x ococFr)d

N

aCbo

l Bzl

[4r ben prq chn (3) cof

SnCL,25" 43Vo

I

COCH3 Cbo

exd

I

CH,

N-Bzl Several

,

Step6

(co

cH3o

o t

(cf. L2, 130).' The cobaltacyclopente5-Alkylidenecyclopentene-1,4-diones with 1, when complexed nedione (2) formed on reactionof a cyclobutenedione with dimethylglyoxime,reactswith l-alkynes to form 5-alkylidenecyclopentene1,4-diones(3). The reactioninvolvesan alkyne-vinylidenerearrangement.Benzoquinonesare usuallyformed in minor amounts.

' '

,

(o

ll

| #

cH---\o

cH,-.t-1o -P(c6H5)3 ',;;,X-x ff,,r ^ cH,----f .t,-\

2E*ll )e" -P1cuH,;,

t"'^\

[ ]cHn"

(Zl-Ketene silyI acetals. Hydrosilylationof acrylateswith any trialkylsilane catalyzedwith Wilkinson's rhodium catalyst results in (Z)-ketene silyl acetals (ZlE > 98:2).3 Example: HsiR., RICH" clRhIP(qHr)]Ll

I

-

coocH3

fi-lNVo

. \_/

2re t.7

((

osiR.

1o.t,

(ZlE > 98:2) ' S. Iyer and L. S. Liebeskind, Am. Soc',lLW,2759(1987). : L. S. Liebeskindand R. Chidambaram,ibid., f0!)' 5025(1987). rN. Slouguiand G. Rousseau, Syn. Comm.,17' I (1987).

4 @l

Chromium crrbene cumplexec

Chromium carbenecomplexes. Cyclopropanation of lrl-dienes.l c,p-Unsaturated carbenes can undergo + 2]cycloadditionwith 1,3-dienes(12, 134),but they can also transferthe car[4 Exclusivecyclobene ligand to an isolateddouble bond to form cyclopropanes. propanationof a 1,3-dieneis observedin the reaction of the c,p-unsaturated chromium carbenel with the diene 2, which resultsin a trans-divinylcyclopropane (3) and a seven-membered silyl enol ether (4), which can be formed from 3 by a to 1 undergoes However,the tungstencarbenecorresponding Coperearrangement. exclusive[4 + 2]cycloadditionwith the diene2.

R3SiO\2, (CO)5Cr

CJL, 25"

I \

ocH3

2 (R3 = TBDM)

pcnleplered :ntene. Ben-

t

t

l

osin'

!'A

osiR3

-\

cH.o -

ocH3 3 (AoVo)

{HBu

I

lWVo

r lrrlane acetals

Bicyclic cyclopropanes.2 Reactionof the Fisher carbeneI with the 1,6-enyne 2 resultsin the bicycliccyclopropane3 (a bicyclo[3.1.0]hexane)in 69Voyield. The l,7-enyne homolog of 2 reactswith I in the sameway to form a bicyclo[4.1.0]-

.zcHt

ocH" E fC-CH (co)scr{ + X CH,

I

E

\

\ar,

-:re(:'-o'"'

2, E = COOCHT

heptane(46% yield).An intramolecularversionof this reactionresultsin a tricyclic enol ether (equationI).

Chromiurn carbene complexes

coHo,8tr

(r)

ocH3

Anthracyclinone synthesis. Wulff and Xu3 have reported a high-yield formal (5) in which the first stepis a benzannelation synthesisof 1l-deoxydaunomycinone of the chromiumcarbene1 with the acetylene2 to providethe naphthol3, which is not isolatedbut treatedwith TFA to inducecleavageof the t-butyl esterand to HC-C--1-21-COCHT (CO)5Cr +

cH3o

o:c_-

I | )'.'

I |

v

l) c6H".7s'. co 2)o,

-/

O+-Bu

cHro cHso

-

l) AgO, HNo' 2) O,, DMF 75Vo

cocH3

Chromium crrbene complexes

93

initiate Friedel-Craftscyclizationto the tetracyclicnaphthol(a). The synthesisof 5 is completedby oxidativedemethylationto a naphthoquinoneand air oxidation of ring C. Cyclopentenones.aReaction of the cyclopropylcarbenecomplex 1 with diphenylacetylenein'l,Vo aqueousdioxane resultsin the cyclopentenone2 as the major product.The carbonylgroup of 2 is derivedfrom a CO ligandof 1, and C' ormal latton n hrch rnd lo

o

fi(co)s* 8.t'

[

1-fo.", t

c'H"-A

tl + CH,:GH.

'7 \' "=-ocH.

79qo

CuH,

cuH;

2 ( t r a n s l c i s= 2 4 : L \

""'l

and C2of 2 arederivedfrom C' and C2of 1. The remainingcarbonatomsof I are lost as ethylene.The two hydrogensat Coand C, of 2 may be derivedfrom water, and indeedyieldsof 2 are lower when the reactionis carriedout in an anhydrous alkynes,the substituentis alwaysatmedium. In reactionswith monosubstituted tachedto C. of 2, a to the carbonylgroup, and the other possibleisomer is not observed.No reactionobtainswith an alkynesuchas ethyl propiolate. (COlsCr:CHNBzlz. @f. 11,400-401). This carbene,like typical Fischer carbenes,undergoesa photolytic addition to imines to give mixturesof cis- and in fair to goodyield. The productsare convertible trans-3-dibenzylamino-B-lactams into 3-amino-2-azetidinones.5 Example: "ttt*-,

acHt

COCH]

ll *t *-rr,

hr. cH,cN A

q

a

tt' | t

l

, | l

f

l

7:4

ohN-srt

887,H:.Pd/c I H"N -CH.

Ht

t

l

l

_,y'_N_ - H olW. D. Wulff,D. C. Yang,and C. K. Murray,Am. Soc.,1f0,2653(1988). rP. F. Korkowski,T. R. Hoye, and D. B. Rydberg,ibid.,ll0,2676 (1988). 1 W. D. Wulff and Y.-C. Xu, ibid.,1f0, 2312(1988). rJ. W. Herndon,S. U. Tumer,and W. F. K. Schnatter, ibid.,ll0,3334 (1988). s C. Borel, L. S. Hegedus,J. Krebs,and Y. Satoh,ibid.,lW,1101 (1987).

94

Chromium(ll) chloride

Chromium(Il) chloride. Olefination of aldehydeswith gem'dichromium reagen*.t Reduction of 1'1reagent(a) that diiodoethanewith CrCL in THF providesa 1,1-dichromioethane yield with in 80-99Vo products of ethylidenation furnish to reactswith aldehydes (equation (E)-selectivity I). high

Rcdr, sulfidesto to aldehy

(r) (I)

crcr' 'rHF,

CH3CHI2

CH3CH[Cr(III)]'

l>.:.<J,,

RCHO 80-9ca

(Etz = 84-98:22-2)

tained in presencer Exam;

Reactionswith other gen-diiodoalkanesunder theseconditionsproceedin low yield; however,additionof DMF (and ultrasonicirradiation)providesa very general method for alkylidenationof aldehydeswith good (E)-selectivity(equation II).

j#g (r) R,cHr2

RI

R,cH[cr(rrr)], "]:.(*, ffi

-H

(EtZ -- 88-99:12-l)

o -llc methvle by CrCl. lactone(c

(1)' pre(E)-Atkenylsilanesand -sulfides.' Dibromomethyltrimethylsilane paredfrom ClSi(CH.). and CHzBrz,is reducedby commercialCrCl, in THF to a reagentthat convertsaldehydesinto (E)-vinylsilanes.A relatedreactionprovides (E)-vinyl sulfidesselectivelyfrom C.H'SCHCI2. (l) RCHO

CrcI,. THF (CH3)rSiCH[Cr(III)], (CH3)3SiCHBr'.ffi

I

;>.

n/H :t-r,(at.,.

slff c6H5cHo

C^H. "

-H

,).:.1.__-SC6H5

H

(ElZ : 82:18\

A gerx involvesc followed I

Chromium(Il) chloride

t

l

rhat * ith

Reductionof a-halo sufues.' In combinationwith LiI, CrC! reducesct-halo compounds,whichundergoselective1,2-addition sulfidesto (o-alkylthio)chromium (equation I). The to aldehydes [1-(phenylthio)ethyl]chromium(Ill)reagent ob-

crct,.Ll.

(r) cH,scH2ct

)

n low i gentatlon

95

?H

rHF p [cH,SCH,cr(III)l## RCHcH,scu,

addition to aldehydesin the tained in this way can undergo diastereoselective presenceof suitableligands,particularly1,2-bis(diphenylphosphine)ethane. Example: l) crct2. Lil

-2) RCHO c6H5scHCHs CI

icJt' -.F.", R

I

OH (synlanti :

80-98:20-2) a-Methylene-y-lactones. Two laboratories{5have reported synthesesof cmethylene-1-lactones by reactionof an allylic bromidewith an aldehydemediated by CrCl, to furnish a homoallylicalcohol, which cyclizesto an a-methylene-1lactone(equationI). . preFtoa o ri d e s

-CH,Br (l) CH2:6/

tooc,H,

II

f't' I

L

tooc,Hs I *o" I

IHTCHOH I t,c"' + C6H5CH9 lCH2:6|

,-rtCuHt

/ \ H,C4\/O - t l

o esters(1), A generalroute to the precursors,cr-bromomethyl-a,B-unsaturated involvescondensationof an aldehydewith methyl acrylatemediatedby DABCO with 48Vohydrogenbromide.5 followed by brominativerearrangement

96

Chromium(Il) chloride

9H, I CHz:CHCOOCH3 + CH3CHO

gHrr

,.CHrBr

C:C

-coocH.

H/

DABCO, E' wqa

./

CH2:C--

CHOH

-coocH,

r)HBr 2) H,SO. --r* -

+

t

l

Iu" H,C-

*H' \

/

H"cy'-\/o ' t l o cis'2 Vinylchromiumcompounds(12,137)'"Thesecompoundscanbeobtainedby undergo reactionof vinyl triflateswith CrCl, catalyzedby NiCl, in DMF They of crcl, sources commercial Some selectiveGrignard-typeaddition to aldehydes. contaminant. metal a contain they do not requiie a catalyst,presumablybecause CH,

QH,

n,Aorr+ R:cHog'

*'\"*'

^-,*"q' G"rr+R2cHo Homoallylicalcohols(S,111-112).CrCl,,preparedinsitubyreductionof reductionof CrCl. (Strem) in THF with Na/Hg, is superiorto CrCl. preparedby aldehydes' to halides of crotyl addition Cr(Il)-mediated CrCl, with LiAlHi for the anli-selectivity'7 high with yield and good in formed The homoallylicalcoholsare Example: OH * CHtn-C#oHrrCHO -f

-

Rt gt

I

^,,/--,rA.'

Loflrt

,

CH,

""r

+ i.4,1

sYn-isomer

Chromiun(Il)

chlorideNickel(ll)

chloride

IT. Okazoe, (1987). K. Takai,andK. Utimoto,Am. $oc.,109,951 ' K. Takai,Y. Kataoka,T. Okazoe,andK. Utimoto,Tetrahedron Letters,E, 1443(1987). r S. Nakatsukasa, (1986). K. Takai,andK. Utimoto,l. Org.,51,5045 { Y. Okuda,S. Nakatsukasa, K. Oshima,andH. Nozaki,Chem.Letters,48l(1985). s S. E. DrewesandR. F. A. Hoole,Syn.Comm.,f5, 1067(1985). 6 K. Takai,M. Tagashira, T. Kuroda,K. Oshima,K. Utimoto,andH. Nozaki,Am. Soc', 10E,6048(1986). ?P.G. M. WutsandG. R. Callen,Syn.Comm.,f6, 1833(1986). 1 I l

t

dht erco -('1. lant.

Chromium(Il) chloride-Haloform, CrC|,-CHX.. E-Alkenyl halides.t Iodoform in combination with CrClr reacts with an aldehydeat 0" to form an (E)-alkenyliodidein 75-90Voyield. Replacementof CHI, by CHCI, and use of higher temp€raturesresultsin (E)-alkenylchlorides.(E)Alkenyl bromidescan be obtainedby use of CHBr, and CrBrt. The E/Z ratio increasesin the order I < Br < Cl, but the rate is in the order I > Br > Cl' Ketonesundergothis reactionvery slowly. Examples: CHI

cHr,. crcr,. I ? tl -JIl{cH3t(cH,),cH:cHI + CHrC(CH2)'CH:CHI cHrd(cH,)rc116 7 5 V o( E l Z = 8 l : 1 9 )

c5HscHo

cH'r''crcrl) 39ftf!

(5Vo)

ctlt-r-n OH (ElZ = >98:.:::x: [o.,sc.H,),] This activationof a C6H.Sgroup as a leavinggroup can also effectvinylcyclopropanation. Example:

o

o prnrh 3)

i

O

. ..,rol".H:cHSCelI, #$-cH:cHSCns

'T. Cohenand M. Myers,J. Org.,53, 457(1988)

102

CrotYltrichlorosilane

trifluoromethanesulfonaie'Cu(OTf )'' Copper(It) 'behydration r cu(oTf), (0.1 equiv.) is an effectivecatalystfor dehydration 25"' The alcoholcan be of primary, secondary,or teitiary alcoholsand of diols at are generallyhigher Yields heptane. or used neat or as a suspensionin decalin areformed (E)-alkenes Saytzeff POCI,/pyridine' thanthoseobtainedwith HrSOoor predominantlY.

OH

-

csi:hcH, l

gs(\y''ca, l

CHz 9:l l8:1

92Vo 48Vo

Cu(OTf)z H2504

hq tbc trq

+ cH;''fcH3

CH,

CH,

(z

atx frq dri! int

Helv"70' 'K. Laali.R. J. Gerzina, C. M' Flajnik,C' M' Geric'andA M' Dombroski' 6070987). Crotyltrichlorosiltne' CH.CH:CHCH,SiCI. (1)' with alreaction with aldehydes'\ Both (E)- and (Z)-1 react Stereoselective improve to an effort In (12' 146)' asthe major products dehydesto givesyn-adducts into pentacoordinated (E)the diastereoselectivity' and (Z)-l'Lnuu"beenconverted Reactionof an aryl aldehyde (2) by reactionwith dilithiumcatecholate. allylsilicates wiitr uotrr (E)_ and (Z)_2showsessentiallycompletediastereoselectivity.

Gq

di

o..l,,o--rA s i i l |

6fl

Li*

Jb\y'

oLi

lE fro

tb(

CH:CHCHI I CHt

+l...--...'

(lI

9-l

2 OH

OH

ArCHO + 2 -

ElZ = 88:12 82Vo EIZ = 2l:79 9lVo

i "/--z

t

l cH, * ei\.,Acu, :

CH,

CH,

syn-!

anti-3 l2:tlu 7tl:22

I M. Kira, K. Sato,and H. Sakurai,Am' Soc',U0' 4599(1988)'

cJ

103

(Z).ond(E)-Crotyldiisopinocempheylboranes

rJtl()n trn be h rg h e r ornred

(Z\- and (E)-Crotyldiisopinocarnpheylboranes, IpcTBCH,CH:CHCH: (1). Brown and Bhat' have prepared the two (Z)-crotyldiisopinocampheylboranes [derived with the methoxyfrom ( - )- and ( + )-pinene]by reactionof (Z)-crotylpotassium are prepared The (E)-crotyldiisopinocampheylboranes diisopinocampheylboranes. in the sameway from (E)-crotylpotassium. The two (Z)-crotylboranesreact with typical aldehydesto give syn-B-methyl(equationI), whereas homoallylalcoholswith highdiastereo-andenantioselectivity alcohols(equaprovidea usefulroute to the anri-homoallylic the (E)-crotylboranes tion II). Thus by proper choiceof the crotylborane,any one of the four possible

(I)

OH

?' c{2cHzBIRcz + cH3cHo----* cHlz\cH, from (+)-c-pinene from (-)-c-pinene

' c .r . 7 0 .

+ cHa\^cH, ^..

Litr

CH,

75Vo 72Vo

95:5 4:96

/cH2BIpc2 + CH3CHO ....---.

(rr) cH

CH,

CHr $lth altmlr()ve rdlnrlted rl.lchvde

:H

9 5: 5 4:96

78Vo 76Vo

from (+)-c-pinene from (-)-cr-pinene

homoallylicalcoholscan be preparedwith high diastereo-and enantioselectivity from an aldehyde. Addition to chiral aldehydes. Brown et al.2 have examined the reaction of the chiral aldehyde2 with the (E)- and (Z)-isomersof ( + )- and ( - )-1. The stereochemistryat the newly formed bond betweenCo and C' is controlled by the productsin chirality of 1. The reactionaffordstwo of the possiblediastereomeric of a reaction al.3 tor 64Vo de. Similar resultshave been reported by Roush et p-alkoxy-c-methylaldehyde.

+ ( - )-(E)-r +(+)-(E)'1

75Vo 70Vo

C'Hi

9H, 9H, y'cH, + cHa\,/-\r'cH, I

9", /\. -CHO+ C:Hi (s)-2

9H, 9H, : : +(-)-(z)-r 73Vo +(+)-(z)-r 79Vo C.,H4\t'4-.-'4'vn' : oH

96:4 9:91

^"

OH

9H' 9t, *' .u/--./--_y'CH, v2rr5

'i;;:

I

oH

(2)' Crotyl- trans-2,5-dimethylborolanes (2) arepreparedby reactionof (Ej- and (Z)-Crotyl-trans-2,5-dimethylborolanes cat(E)and (Z)-crotylpotassium (1) with B-methoxy-(R,R)-2'5-dimethylborolane CH"

l

K

'

. _

I bocH,+ /\Y' (E) Y

cH. I BF,.o(c,H,), flr,a-4Cff, (-/ "CHr

CH, (E)-(R,R)-2

(R,R)-1

CH.

. K * (R,R)-l + \./ \jjjiJ

(z)

I

OL-,o' : 'cH, (z)-(R,R)-2

alyzedbyBF.etherate.(E)-and(Z)-Crotyl-(S,S)-2'5-dimethylborolanescanalso be preparedin the sameway from (S'S)-1' aldehyde Asymmetriccrotylboration.t The reactionof an achiral,unhindered with(E)-(R,R)-2givesanti-andsyn.homoallylicalcoholsintheratioofabout20:1; OH (I)

-u; C,H5CHO + (E)-(R,R)-2

qH'\ACH' CH, = l3:l) (96%ee,antilsYn OH

-;; (II) C,HsCHo+ (Z)-(R,R)-2

OHffcH' CH, (86Voee, antilsYn= l:13)

(Z)-2 results is obtainedin95-97Vo ee' The reactionwith the major dt?ri-product insyn-andanri-homoallylicalcoholsalsointheratioofabout20:1'andthemajor obtainedwith proiuct is formed in ge-glTo ee, with the highestenantioselectivity hinderedaldehYdes.

s t (

Crotyltrimethylsilane

105

The diastereofacial selectivityof (E)- and (Z)-(R,R)-2 with the chiral aldehyde (R)-2,3-O-isopropylideneglyceraldehyde (3) is approximately 35:1and 50:1, reOH n rrf cat-

ffAr^.",

+ o/^\'-'cHo + (E)-(R,R)-2 cH,fo cur\O

cH,

CH,

CH,,

(97.9Vode)

(R)-3

\u,

(R)-3 + (Z)-(R,R)-2---.-*

(96.17o de) spectively.Thesediastereoselectivities are amongthe highestreportedfor crotylboranes.The diastereoselectivity is markedlylower in reactionsof (R)-3 with both (E)- and (Z)-(S,S)-2becauseof mismatching. l J . G a r c i aB, . M . K i m ,a n dS .M a s a m u n e O , l .r g . , 5 2 , 4 8 3( 119 8 7 ) . n Jlso e h rd e : 1 ) :I :

Crotyltrimethylsilane(1). Reaction with glycals.t (E)-1 reactswith glycalsin the presenceof BFr etherate to give pyranssubstitutedat Cr with a 3-methylpropenylgroup that is lrans to a substituentat Cu. Example: .OAc

OAc .OAc 'H

CH2OAc

CH, (E)-1,BF,

CH2OAc

--t*-

T

3:1

HrC? C1'anti

..OAc CHr. rcsults : major ed rrith

CH2OAc HrCt/ Ci syn

1{16

Cymomethylenctripbenylphocphorene

Arefinedversionofthisreactionwasusedtoobtainopticallyactive3from 4' a subunit of glycal2. This product is readily convertedto the tetrahydropyran the antibioticindanomYcin.

CH,

cyclic ur a synthc

Hr(

(t) 2+

I H . J . B

4 'S. J. Danishefsky, S. DeNinno,andP' Lartey,Am' Soc"f09' 2082(1987)'

Cyenot Preg

2l sd

Cyanomethylenetriphenylphosphorane' (1) can be deprotonated Nltriles.t Cyanomethylenetriphenylphosphorane withsodiumbis(trimethylsilyl)amidetogivesodiumcyanotriphenylphosphoranto give a wide variety of vlidenemethanide(2). ri* ytio" anion can be alkylated (colts)rP:cHa*

NaNlsi(cHr)rL. Na.[(c6H5)3i-CcNl

1

acid und reactioo stituted retenti('

(r) (c

2

l**

I t

the sra. with an

R

* l

(cJt5)3P-QCN 3

withaldehydes (3),whichreactasexpected cyanomethylenetriphenylphosphoranes of nitriles.The ylide anion2 is alsousefulfor synthesis to give cr,f_unsatuiated P\ 2 + Br(CHr)s< tozla

+ / o > H .---_ cr (c6H5)3P-c(cH')'{ I

J*

b-/

J . P h :\ ofi

Cyenotrimethylsilone N-

m of

H

I Q

H -Q(CH2),-CHO I , l l s 2 % C N J

Itc",l,i L Cl-

4 cyclicunsaturatednitrilessuchas 4. Reactionof 2 with carboxylicestersprovides a synthesisof acetylenicnitriles (equationI).

(I) 2 + RCooRr .------(CuH,),i-a-con

RC:CCN + (C6H5)3P:O

#A

CN tH. J. Bestmann Angew.Chem.Int. Ed.'26.79(1987)' andM. Schmidt, :H. (CH.),SiCN. Cyanotrimethylsilane, Preparation:' 2(CH3)3SiCN

2(CH3)3SiCl+ H2SO4:rHci [(CH])3SiO]2SO, #

rted ranI trt

substitution of p-nitro sulfides.2 p-Nitro sulfidesin the presenceof a Lewis The reactionswith eitherallyl- or cyanotrimethylsilane' acidundergodisplacement subis then which intermediate, reactionis consideredto involve an episulfonium stituted at the more positive carbon (equation I). The reaction proceedswith retentionof configuration,and anri p-nitro sulfidesreact much more rapidly than NCSi(CHl)l

(I) (cH.)"c-cH,No, i91------_(cH3)rc-cH2sc6H5 + \-,

.

\---Jlzi

I sc6H5

64qc

CN

(cHr)rc-cH2cN 73:27 SC.g,

the syn-isomer.This reactioncan be usedto effectcyclizationof B-nitro sulfides with an aromaticring (equationII).

l\ de\

sl\ of

CH, (trans,l00Vo) I J.-P.Picard,R. Calas,and J. Dunoques,Org. Syn.' submitted(1988)' 2 N. Ono. A. Kamimura,H. Sasatani, and A. Kaji, J. Org.,52' 4133(1987)'

1$

CycloproPenone ethYl hemiacetal

(1)' Preparation'' Cyclopropanoneethyl hemiacetal with lithium of I with CH'MgBr and then Tricyclic heptanonrei'l-ii"'"uttlon 2 can product 3' The minor resultsin 2 and the tricyclicproduct cyclohexenolate lithium and by further reaction with CH3MgBr be converted into 3 in high yield

r,& 1) CHrMgBr

Ho

',aYo'' oc2H5

V l\ I

I

witl tlrc

I

oH+ / \

l----.)

2 (r4Vo)

I (Avo)

cyclohexenolate.Theformationof3isbelievedtoinvolvegenerationofcyclopro. reactionswith the enolate' panone,which underg";t ;;" consecutive Org'Syn"63' 147(1985)' 'J. Salaiin andJ. Marguerite' 8313(1986)' : J. T. Carev,C' Knors'""ii'' n?iqtirtt'Am' Soc"lm'

nq fo rl ro

I

D d b

num a,ln llu nl

l,E-Diazabicyclo[5.4.0lundecene'7(DBU). lr}-Elimination.r The dehydroiodinationof 1-iodo ketonesor f-iodo esters occursreadilyonly when the proton and with DBU at25" to form cyclopropanes the iodo groupcan adopta w-shapedgeometry.Thusthe cyclopropane1is formed

DBU. I hr.

DBU,5 min. 88Va

I

Ts

N

6'7Vo

I

Ts I

2b

r*l*o.,.",u

'l*};""

CH3C:O

9,H'9:o

DBU.5 min.

,P.

\"/

I

Ts 3

-

(rr,

I

Ts

readilyfrom 2a in which the hydrogenand iodine havethe syn-orientation,but is formed slowly and in tower yield from the anti-isomer2b. The cyclopropaneI is also formed from 3, but only with a strongbase;reactionof 3 with DBU results in a 1,2-elimination. ' M. Mori.N. Kanda,Y. Ban,andK. Aoe,l.C.S.Chem'Comm'.12(1988).

Diazomethane. Insertion into Si-.l bond.t Reaction of trimethylsilyl iodide or triflate with diazomethaneresultsin insertionof a methylenegroup into the Si-I or Si-OTf bond (equationI). Similar insertioninto (CH,)rSiBrrequiresZnBr, catalysis.

110

Diborane etner

-78+-ro') (cH.)isicHrx + N2 (I) (cH3)3six+ cH2N2

X = I

65Vo SlVo

X=OTf

(1988)' 'J. G. LeeandD. S. Ha, Synthesis,3l8 obtained by Dibenzyl peroxydicarbonate' (CfI5CHrOCOr), (1)' The reagent is to water is stable reaction of benzyl chloroformatewith H2O, in a basicmedium. It and is not readily detonated. c-hydroxy u-Hydrory ketones.r The reagent oxidizesenolatesof ketonesto to is comparable ketones,isolatedas the carbonatesin moderateto good yield. It oxazolidinone for asymmetricoxidationof 2-(phenylsulfonyl)-3-phenyloxaziridine carboximides. Example: O li

O

r)KNlsi{cH.),;

coH,:A c"u, #

ll .nt'y^a.",

efiect leaivi atab select transi

OCOBzI

tl o

rM. P.GoreandJ. C. Vederas' l' Org.,51'3700(1986)'

IE.J.

Diborane. with a rechiral orazaborolidines.t Enantioselectivereduction of ketones is now known agentpreparedfrom BH, and the chiral vic-aminoalcoholI (12' 31) toinvolveanoxazaborolidine.ThusBHrand(S)-l,derivedfromvaline'react rapid|yinTHFtoform2,m.p.l05-ll0",whichcanServeasanefficientcatalyst CH, \

zcnH'

H XC"H.

H,N

cH. fH'.

CH:

,CH,

OH

(s)-1

BH, -:nl

lnH'

BH,.

coH,

")-rt""' I b"r,

,lu-*til 3

(0.025equiv.) for reductionswith BH.. ThusBH3(1.2equiv.)in combinationwith 2 via 3' presumably ee, 95Vo in can reducea typical ketone to the alcohol of BH, with reaction by (5) obtained is A more efficientbicyclic oxazaborolidine (0'6 equiv') BH' and (0'05 equiv') 5 of (S)-diphenylprolinol(4). The combination

1,l-Dl A ZnlTr reacts which of ketr prepat it read hydror Err

{itanium(lV) chloride-Tetnmethvlethvlenediamine

fl .,CuH, € \NTc.H,

BHr

H O H

(s)-4

111

CoH,

l * o

N-^/ \g'H 5

6

t ?

d bt' rater

Jn-n, poHs CuH:

lroxv *e to none

H-\,.'oH

ni""n,

o

\--,NlBaH

-

HrBr

:

."s2

(R)-7 (88-97Voee)

effectsrapid reductionof a variety of ketonesin high yield and >907o enantioselectivity.The enhancedreactivityof5 is associated with the strainofa doublebond at a bridge head, which is relievedon formation of the complex6. The enantioselectivityof reductioncan be explainedon the basisof a six-memberedcyclic transitionstate(as formulatedin A). l E . J . C o r e yR , . K . B a k s hai ,n dS .S h i b a t a , A m S.o c . , l l ) 9 , 5 5(5119 8 7 ) . hareknown . react u lalvst

H l-H.

iequiv.) lH, with i equiv.)

I'l'DibromoalkanerZinc-Titanium(IV) chloride-Tetramethylethyrenediamine. Alkylidenation. These four reagentsin the approximateratio of RCHBTT/ ZnlTiClolTMEDA: l:4:2:4 reactin THF to form a metalcarbenecomplexthat reactswith the carbonylgroup of estersto form alkenyletherswith (Z)-selectivity, which increasesasthe sizeof the R groupof the reagentdecreases. Alkylidenation of ketoneswith these reagentsshowslow Z/E selectivity.Although the reagent preparedfrom cHrBrr-zn-Ticlo is usefulfor methylenationof ketones(l:2,339), it reactsin low yield with esters.Thesecomplexesalso reactwith lactones,but 1hydroxyketonesare formed as well.' Examples:

o tl

Zn. TiCL

coHs---H -C:C -CH, (CH3)rHCO(ZlE = 92:8)

tYru:^, cuH,iocH(cHr):+ CHrcHBr, 88Va

Itz

DibromomethYllithium

.,r,.,{o\

T1 * + CH'cHBrz c,",AoAi"

der ift

+

isl

tat,

9& 3 t'

(43%,ZtE:85:15)

tol

OH I

CrH IsCHCH 2CH2CCH2CH3

oft the hor

o (4rVo) Atkylidenation o! silyl esterc,2 Application of this alkylidenation processto silyl estersprovides(Z-)silyl enol ethersstereoselectively' osi(cH3)3

osi(cHr)3 aHrc\o

Zn.ricL.

+ Br2CHCH2c6t,I

a"/*ftH2c6Hs H ZIE -- 92:8

o /B' " ll c.H/\-r\osi(cH3)3 + Br,CHBur*' c.Hi\Aosi(cHr)r (z), rWvo

Dibromomethyllithium,LiCHBr2, dichloromethyllithium. Dibromomethyllithium can be generated from cHrBr2 with LDA as base rather than BuLi, used for generationof dichloromethyllithiumfrom CHTCL. Diastereoselectivehomologation of chiral alkylboronates (cf. 12, 80-81). Investigationsof this reactionhave been carriedout mainly on boronic esters(1)

CH,

direc (R= andd but in Th and in under 2-azid carbor

Dibromomethyllithium

lcHrcHl

5 to |r()cess

113

derivedfrom ( + )-pinanediol(from a-pinene)and formulatedfor convenienceas indicated.'Reactionof L with LicHCl, at -100" givesa boratecomplex(2) that is rearrangedby znCl, (1-1.5 equiv.) to a (lS)-1-chloroalkylboronic ester(3) with 98-99Vodiastereoselectivity. Nucleophilicdisplacements (RMgX, ROLi, RLi) on 3 yield a new chiralboronicester(4) whichcanbe further homologated.Application to the synthesisof a chiral vic-diol(5) is shownin equation(I). The configuration of the new chiral centersis determinedby the pinanedioland by the order in which the substituentgroups are introduced;but the unique feature of boronic ester homologationis the possibilityof unlimitedrepetitionwithout removalof the chiral

-

-o\

X I -O--'. .Znct, ".. , _-B1 rir R>C
98Vo ee after one and LiOH to (R)-c-hydrazino acids(E), which

Dit

I pler silao red 129-

crystallization.

c.u,.To*/

R

6rtrc".t. | cH,?N(cH,); Rt.."H Hooc^NHNH2 (R)-r (1984)' I W. J. Paleveda, F. W. Holly' andD' F Veber'Org'!yn" 63' 171 (1986)' z D. A. Evans,T. C. Britton',n.-L.boro*, andJ. i Dellaria,Am. Soc.,10s,6395 (1986)' ibid',lM' 6397 ' L. A. TrimbleandJ. C' Vederas, aC.Gennari,L.Colombo,andG'Bertolini'ibid''108'6394(1986)'

o

but i T dh{

(c

Dicarbonylcyclopentadienylcobalt' dihydroindolesinvolves Dihydroindoles.' A nou"l synthesisof fused of alkyneswith the 2'3-doublebond of N-alkynoylated 12 + 2 + 2lcycloaddition pyrroles.Thereactionofl.withbis(trimethylsilyl)ethyneresultsintwodiaster-

lr-i]

CpCo(CO)r (cH.).Si - ' - C 23" +' 48Vo

\N/

si(cH3)3

ill

I

olcH,;,c:cu 1

C (cH3)3si t

Ittt hx

eomericcobaltdienecomplexes(3),whichareconvertedtothesa mefreediene indole by excessCAN' on oxidatonwith CAN (1 equiv') or to the aromatized rG. S. Sheppard 'l' Org''51'5496(1986)' andK. P.C' Vollhardt

6d: a ! rI ril

Di-p-carbonylhexacarbonyldicobalt

RaneY . Thus g r r e7 r TFA t e ro n e

Il7

Di-p-carbonylhexacarbonyldicobalt,Coz(CO)s. Medium-size cycloalkynes.l In the presenceof BF. etherate, a cobalt complexedpropargylicether can undergoan intramolecularalkylationwith an allylic complexedcycloalkynes.This silaneto provide six-, seven-,and eight-membered (10, reactionis an extensionofpropargylationof allylsilanesto provide 1,5-enynes

r29-r30\. .CH, BF,.O(CrH.): cHrctr

(

L(CHr)" ,|,|F.":(co)" ., I, n=1,2 n = 3

55Vo 67Vo

H \HNH,

Oxidativeremovalof the Cor(CO)uligandof 2 doesnot resultin a cycloalkyne, but 2 can be usedas suchfor annelationto complexproducts. This reaction can also be used for exocyclicintramolecularalkylation of an allylic silane,suchas the cyclizationof 3 to trans-4with completestereocontrol.

F r lelt6).

co,(co)6 IT:IE t " ' ocH3

(CH3)35iCH,CH:CH(CHz),qHc4ccuH,

tnr olves mor lated I dtaster-

H,t.

-Co,(co)u

/-'.,2'u't

I

I

V'CH:CHz 4 8e7o l(cHtlNo

CuH, 'CH:CHz 5

frec diene r ('AN.

Medium-ring acetyleniclactones.2 Cyclizationto medium size acetyleniclactonesis difficult becauseof geometricconstraintimposedby the triple bond, and rings. Surprishasbeen consideredpracticableonly for at leastfifteen-membered is cyclized with Cor(CO)o when complexed acid I ro-hydroxy ingly, the acetylenic by Mukai2 lactone acetylenic yield complexed to the seven-membered in 28% chloride (8, 95-96). The yield is esyama'sreagent,2-chloro-l-methylpyridinium sentiallythe sameas that observedin lactonizatonto a complexed10-membered

1lE

Di-p-crrbonylhexecrrbonyldicobelt

, s .L

oH

fH(cH3)'

I -* Hooc(cH,)'-.T".;3lcH(cH3)2 .I,' )ts."t.or.' t

DicI'

n

,

geometricconstraints acetyleniclactone. Evidently a cobalt-alkyne group has less than an alkyne grouP. via The samepaper reportsanotherroute to 1l-memberedacetyleniclactones with of 3 an intramolecularretro-Dieckmannreaction (equationI). Thus treatment

(I)

:N.E 1 M ,E

with d of rn lectirr Er

c

aYo'o) WCo2(Co)u

K.V ( t9E6

The unNaH (1 equiv.) at 25oresultsin the complexedlactone4 in Tlvo yield' compound' isolable is a stable, complexedlactone Pauson-Khand cyclopentenonesynthesis.3The cycloaddition of an alkene with an alkyne complexed with coz(co), usually furnishes a mixture of two cybe imclopentenoneswhen the alkene is unsymmetrical.The regioselectivitycan with the coordinate can that heteroatom a bears alkene proved markedly if the regioyield and the improve can ligands nitrogen and sulfur cobalt complex. Both control of this reaction. Examples:

Ilkfl. bl rea R' (2) rrt

C^H.

I'

C6H13CH:CH2

+ C

ill c

CodCo)s Q.fl,.

4

rBVo

t3l arx r\ prcfl r)f 2 to

H

QoHs I

CH35(CH2)rCH:CHz + C

_G

e g u r \ .I

llt c H

o

ll

cHrs(cH2)2

CoHs + 1 8 I:

'A=-CuHt

\

t

l

\ i l cHrs(cHr);

phenoxide 119 Dichloroaluminum 'S. L. Schreiber, (1986). T. Sammakia, andW. E. Crowe,Am. Soc.,10E,3128 2N. E. Schore (1987). andS. D. Najdi,,r. Org.,52,5296 3M. E. Krafft,Am. $oc.,110,968 (1988).

!

Itrt CO)o

rnc constraints [c lactones via rment of 3 with

Dichloroalane,Cl2AlH. Hydroalumination. Monosubstitutedalkenes undergo hydroalumination with dichloroalanein the presenceof (CrH.)rBor C.H,B(OH)2.Hydroalumination of more highly substitutedalkenesproceedsreluctantly.The reactionis regioseundermild conditions. lective,andthe productsreactwith a varietyof electrophiles Example: c16H2rcH:cH2 + cl2AlH -9

1c'oHlcH:cHrAlcl'l f I

c'rH,,ott

C,rHr.:;fi;,;

'Co-(CO)o

rK. Maruoka, Am. Soc.,10E'6036 H. Sano,K. Shinoda, S. Nakai,andH. Yamamoto, (1e86). rreld. The unn of an alkene (ure of two cYirrtr canbe imrdrnatewith the rreld and regio-

Dichloroaluminumphenoxide,Cl2AlOCoH,(1). This aluminumreagentis prepared by reactionof CH.AlClt with phenolin CH,CI,. Ring enlargement.t Treatmentof an c-(silylmethyl)cycloalkanecarbaldehyde (2) with a Lewis acid resultsin a one-carbonring enlargementto a cycloalkanone oHC_ _CH2Si(CH.).

t

-

cHrsi(cH.).

+ /-K

( ) '(CH,)L

\.r,1,,

o

3

)'-.,^, \ /

OH I .CH,

2 a , n : 3 b , n : 9

4

l00Vo 85Vo

phenoxide (3) and smallamountsof the 2-methylenealkanol 4. Dichloroaluminum of 2 to 3. Ring enlargement is preferredover CH.AlCl, for selectiverearrangement (2 of 2 to the methyl ether (5) of 4 is best effectedwith methoxytrimethylsilane equiv.) and trimethylsilyltriflate (l equiv.).The dimethylacetals(6) of 2 also

o )-,,y-c6H5

\ l l

1 l - ):

9CH,

( -,CH2Si(CHr), ^z-*1, cHicl:' A

CH.O-I2< RC-CH ct'

/H

br

Pd{o}

+5

Ht

):.( RC-c

/H

+:#; RC-C-C:CH

cl

I A. S. KendeandC. A. Smith,,/.Org.,53,2655 (1988).

:rlr lated u r c db Ya acrdat 0o

Dichloroketene. Bicyclo-y-butyrolactones.t The reaction of keteneswith chiral vinyl sulfoxidesto obtainopticallypure 1-arylsulfanylbutyrolactones (Ll, 177)canbe extended to a synthesisof bicyclicbutyrolactones. Thusthe arylsulfanylgroupof 1 undergoes

Dichloroketene

"'tY"' f'l: lrt=o

SC,H,

1)Cl,c:c:o

o.

Hrc

2) ZnlCu

{

ls

&-7OVo

BurSnH AIBN

o' "*'

c2H5o2c

a,r,ooaXooc2H5

the ocupar

CH,

c c2H5o2c

CorcrH, 2 ( a t B= 1 ' 2 1

from t ones. are re zinc a Er

form two epimericcison radicalcyclization(Bu,SnHand AIBN) to displacement fusedbicyclicbutyrolactones(2).Lewisacid-catalyzedcyclizationofthel-aryl4' 3 resultsin a singleisomerof the cis-fusedlactone sulfanylbutyrolactone

ocH3

CH,o

[>.

SAr

BurSnOTf , 85Vo

co2c2H5

cis-4 allylic ether (1)' prepared EnantioselectiveI2 + 2lcycloaddition.2 The chiral cycloaddition enantioselective undergoes from (1S,2R)-(+ )-2-phenylryilohexanol, ( - )-2' This pure optically ' with dichloroketeneto t rrni,tt, after one crystallization perchlorategives afterring expansionandexposureto chromium(Il) cyclobutanone

i.HrCHr-u c' crrc:c:o' o/

\H,

cl ....cH, cuHncHr-p (-)-2 (9s:s)

J P . A E A H 'A ., R L .

Llu al to st'!

ihtoro rnrotu

2,3-Dichloropropene

o

tl

cl-1\ \\ l..cu, ato, (+)-3

)-o C:H. l)

reric cis: t-arylI

o

&?i', a,:,',

CH;

(+)-s

(-)-4

the c-chloroenone3, which can be convertedto ( - )-c-cuparenone(a) or ( + )-9cuparenone(5). Cycloaddition to alkynes; cyclobutenones. This ketene when formed in situ from CCICOCI and ZnlCu, reactswith alkynesto form 4,4-dichlorocyclobutenones,3which can rearrangein part to 2,4-dichlorocyclobutenones.a Both products are reducedto the samecyclobutenoneby Zn(Cu) in HOAc/pyridine (4:1) or by zinc and aceticacid/TMEDA.S Example:

9H, I C

ill

C

cH3\4'o ll I +cl2c:c:o#

+

, .-J4o 'l:1

cH5cr

."/-ft' 4:l

CH, =Q

,,,1fi{::]., tt')_,fo CH{-

. prePared It.raddition - t-2.This orrle gives

rJ. P.Marino,E. Laborde, (1988). andR. S. Paley, Am. Soc.,110,966 ' A. E. Greene, F. Charbonnier, M.-J.Luche,andA. Moyano, ibid.,l09,4'152(1987\. r A. Hassner (1983). andJ. L. Dillon,Jr.,J. Org.,4t,3382 I A. A. Ammann, (1987). M. Rey,andA. S. Dreiding, He|v.,70,321 5R. L. Danheiser, (1988). S. Savariar, andD. D. Cha,Org. Syn.,submitted

2,3-Dichloropropene. Biaryl synthesis.t This reagentpromotescoupling of aryl Grignard reagents to symmetricalbiaryls in 70-95Voyield with formation of allene and 3-aryl-2chloropropeneasco-products.The reactionis retardedby galvinoxyland evidently involvesan electron-transfer from the Grignardreagentto the dichloropropene.

lyl

Dichlorotns(triPhenylphosphine)ruthenium(Il) .rcl

2ArMgBr

* CH2:Q'

25. - rHF. -

(

CH,CI

+ t"':t(ltt'o' Ar-Ar + MgBrCl* CH2-C:CH2 (10-957o) 29' 1293(1988)' I J.-W. Chengand F-T' Luo' TetrahedronLetters' 10' 140'' 12' 179'

coupleswith adduct (1) of 2-chloroallylamine Allytic amines.| il;.;;"," = (c'H')'P(cH')3P(c6H5)" of Nicl'(dpppj' +oo Grignard reagentsin t'e ire'-ence allylic amines' to flrm, after deprotection' ExamPIe:

1,4-Dichloro-1,L,4,4'tetramethyldisilylethylene'

CH: il

rd

cH3pH3 \*/ sr___.

cH'' t1/cH' ",!.!- g

crAcH,{r,J + RMgBr

ll

Si--I

CHr{ -"'^),i

/")", I

ft'

R.

ct'

5s-ma lu'o. CHt ll

RdcH.NH, Wagner"l'Org''52'678(1987)' J' R' McCarthy'andE' R' I T. M' Bargar,J' R' McCowan'

bc

rt Dichlorotris(triphenylphosphine)ruthenium(Il)' o.to,'dichloroesrcrcrand acids' oy unroturotrd Intramorecurar cycrization metals is a wellin tt " pr"*"*e of transition ,;;;t f,uro.uriln, ot Adctition knownradicaf'"uttion'Weinrebetal'thavenowreportedanintramolecularversron substratesare the ct'a-dichloro lit"itc lactones'rypicai "' *'"" cyclic to leading by reaction of ethyl lithiodi. *io 2, readily uiui'uut" ",...ai"r,io. .t," o, 1 at 160"with ester wt'"n i is heaied in benzene ;-;;;;ji-p"ni"n"' *ith chloroacetate esters3 and 4 are obtained' of epimeric t't-Oi"f'foto ti*iu'"' catalyst, metal a catalystand concentratton i are dependenton the yi"roJo?;; una and ratio The in the presenceof Ru(II) ."i"r products formed "*",n" 4 and the 3 gives but 1, of same conditions tytti'ution ot itno"t the h:;;;;; catalvst'' Fe(II) yield' bicyciic 1-lactone5 in high

d

R

R:

Dicyclohexylcrrbodiimide

cl cl

/.-\rcooR

CI c6tl, 1d)" cat.

KCH, CI 'CHlAr

/^-+,COOR

1 \

l

l

*1"'cH,cr H

I, R = C:Hs

2 . R = H

Ru(II)

/

\

CI /-J....COOR l

-f,l .",.'

3 4l%o

4 36%

Ru(II)

|es with tC^H.)r'

H 5,94Vo Indole synthesis.22-Aminophenethylalcoholscyclizeto indolesin refluxing toluenein the presenceof this Ru(II) catalystin 75-100%yield.

'T. K. Hayes, A. J. Freyer,M. Parvez, andS. M. Weinreb, J. Org.,5f,550l(1986). ' Y. Tsuji,K.-T.Huh,Y. Yokoyama, (1986). andY. Watanabe, .LC.S.Chem.Comm.,1575

6 - s( 1 9 8 7 ) .

d acids. ts rs a wellllar version .o-dichloro hrl lithiodiNr160'with e obtained. ncentration Ru(Il) and n! givesthe

Dicyclohexylcarbodiimide(DCC). Invercion of configuration.t The configurationof 4 secondaryalcohol (2) can be invertedby reactionwith dicyclohexylcarbodiimide (1) to form an isoureaether (3), which is allowedto react, without isolation,with formic acid with formation of the ester4 with invertedconfiguration.

'"i[!f&'": * C6H11N:G:NC6H11 :>r..:.. [l ^ ^]ttt- U - L :(.NC6H" Il sX* R2"'OH o-rs"" -NHCuH,,l ,

I

L

,

o tl + c6H,,NHdNHC6H,, # 'H ]]>/icHo R2 4

'H _1;/..:" R2 5 (>99Vo ee\

132

Dicyctohexytcarbodiimide4-Dimethylaminopyridine

N-Tosytamidesandlactams.,DCCincombinationwith4-pyrrolidinopyridine(4-PPy)effectscondensationofcarboxylicacidswithsecondarySulfonamides intramolecularversion of this to provide N-tosyl amidesin 75-90Voyield' The in 60-90Voyield' lactams reactionprovides4-, 5-, and 6-memberedN-tosyl

clizatior and the vides I

r G .S r q

Example: C,H.. "'--(

C'H'.. '-l CHTCH2OR Dcc4-PPv'

-*-

cHrcl' 25"

I I Hooc NHTs

-r'CH' CH2OR

| |

ofN-t,

(198'7)' rJ. Kaulen, Angew'Chem.Int. Ed',26,"173 4,613' 619(1988)' 2D. TanneranJP. Somfai'Tetrahedron,

Dtcydol The n Bcr. -5(f to

ocH

Dicyclohexylcarbodiimide4-Dimethylaminopyridine' Macrolactonization(13,107-108).Thefinalstepsinatotalsynthesisof(+)(1), the aglyconeof erythromycinA (2)' involve cy(9S)-dihydroerthythronolide OH

o

Cp..T

v

C H,

ICH.

Yt l o

"o

complcr to form a hasonly hydrolpi before h1 Ttrc o COnuenc

Dicyclopentadienylmethylzirconium chloride

L!3

lop\ rlantides of this

cfizationof the secoacid (3), which procededin 64Voyield using DCC, DMAP, and the trifluoroacetateof DMAP. Deprotection of the resulting lactone (4) provides f. in 56Voyield.

I

lG. StorkandS. D. Rychnovsky, Am.Soc.,109, 1565(1987).

Dicyclopentadienylmethylzirconiumchloride, CprZr(CHr)Cl (1). The reagentis preparedby reaction of (CprZrCl)rO with AI(CH3)3Q5Voyield).1 Benzyne zirconocenccornplexes.2 This reagent reactswith an aryllithium at - 50" to form an intermediate a that losesmethane at 25oto give a zirconocene

r)BuLi

?tt, iL,f(+)rlrlre C]-

2)r'rHF,[ ?t"'ft' lrr\..Zrcp,

..\.,-B.

U I U cH,

cHrcN +

::; ZrCp2

9cu'

>\-'rA) H'o' o l*',-

rrI ll 's{2

lr{e,

4

3a

cH'J

3b

","111,i,", )H

5a complex(2) of a benzyne.A nitrile reactswith 2 with insertioninto a C-Zr bond to form metallacycles 3a and/or 3b, dependingon stericfactors.When the benzyne hasonly oneortho substituent,the corresponding 3a is formed preferentially.Acid hydrolysisof 3a providesa substitutedacetophenone 4a. Reactionof 3a with iodine beforehydrolysisprovides5a. The complex2 also reactswith ethyleneto form the metallacycle6, which is convertedinto a benzocyclobutane (8) in two steps.

DiethoxytriphenYlPhosPhorane

l-..r,.\ l2

CHr:CH'

?'"'

?", BuLi --a\

l t l' # A . 2 )

\CH,)a\V

IXr

mol wid I

7

Diethoxytriphenylphosphorane,(C.Hs).P(OC,H5),(1)' The phosphorane is obat 0-70'' tainedby reactionof diethyl peroxide(caution)with triphenylphosphine Cyclodehydrationofdiolstoetherc'1,3-,L,4-,and1'5-Diolsreactwithlto

Ho(cHr)"oH* t

n=3-5

cH?cr'[ ?t't' -c'ri'oH' lcuu,-{1c,u,;,

I l=:"

-ocH,(-)cH,

" ". L--- fi.",,"orl

\it''"

+ o:P(c6H5)3

' J .t

n=l-J

The reaction of 1 with 1,2,4-butanetriol form ethers via acyclicphosphoranes.r resultsin an epoxideand a hydroxyfuran:2

DT

' HocH,!;cH2cH2oH ' \(cH,),oH

Ho"

SlVo 19Vo

with \ , 4 - O x a t h i a n e s . sD e h y d r a t i o no f 2 , 2 ' - b i s ( h y d r o x y e t h y ls)u l f i d e s in moderate 1,4-oxathianes to route a stereoselective provides (c6H5).P(oC,H,), (isolated)yields. Example:

a^)

'oH

\.Ar-(cH')'oH

(cJ|,hP{OC,H.)r

H

41qo

, l

|

|

(2)r

.di. ehu

c.ll

(

s

\_rAr/ H

tx €t t1

Diethyl isocyanomethylphosPhonste

OCH /\

i l l

v

135

Diethylaluminum ethoxide, (CrHs)rAlOCrHs(1), availablefrom Aldrich' Intramolecular aldol condensationr This base can be effective for intramolecularaldol condensationof extremelyhindereddiketonesthat resistcyclization with the usual bases. Example:

t 9 - l) . -1 , 1 7( 1 9 8 7 ) . rrane is obrneat 0-70'. act with I to

r-BuO r O:P(CoHs)r

r-BuO I J. W. ApSimon and R. F. Lawuyi, Syn.Comm.,17, 1773(1987).

{-butanetriol

OH

o tl

Diethyl diezomethytphosphonate,(CrH.O),PCHN, (1). Furans.t Reaction of c,o-dimethoxy ketones with 1 affords a dihydrofuran (2) presumablyvia a carbene(a) that insertsintramolecularlyinto a C-H of an adjacentmethoxygroup. The reactionoften resultsdirectly in a furan, sincethe eliminationof methanolfrom 2 is facile.

I

s u l r r d e sw i t h s rn moderate

*.,,

QHt

nrO, quant.

h

(o)

3

I ro? 5210(1985).

'S. R. Buxton,K. H. Holm,andL. Skattebdl,Tetrahedron Leuers,8,2167(1987).

(1). Diethyl isocyanomethylphosphonate reagent (availablefrom Fluka) converts alWittig-Horner This Aldehydes.t which can be hydrolyzedto isocyanides, c,p-unsaturated into dehydesor ketones aldehyde. homologated the one-carbon

1,&DihYdrotetnmethYldisilrzene

I

Example:

requ

*).:"r*:. N:c-!il-H.-%

#

Polrl hoo hvd H,P (3).

f;""ro

l J. Moskal and A. M. van Leusen, Rec' Pays"Bas"106' 137(1987)'

RuHz[P(cuH')J'(1)' Dihyridotetrrkis(triphenylphosphine)rutheniurn, Amides.|ntrrepresenceofthiscatalystnitrilesreactat160"withaminesin in 75-95Voyield' an aqueousmediumto giveamidesin a singlestep Example: CH3O\.,'\',(CH2)2NH2

BzlO,grl.CH2CN

* l l

Y t l

I

( c.H

I'x'o'-

- #

silN

cH.oV

cH30YAY,) szt/2

98Vo ee.

oH? (I) RcHo + 3 R = Pr

-t8',

9l%o

R^

?"

LtAlI5 R'\/cH2oH sc(c2H5)3 : : CH, CH, anrilsyn = 33;l

98Va ee

The normethyl analog(4) of 3, preparedin the sameway from an ethanethioate, also reacts with aldehydesto form aldols but with lower enantioselectivity(8993%ol.

(D RcHo +affi

R

? ' ' ?sc(c2H5)j 89-93Voee

rT. Imai, T. Tamura. A. Yamamuro,T. Sato, T. A. Wollmann,R. M. Kennedy, and S. Masamune,Am. Soc.,lM,7402 (1986);S. Masamune,R. M. Kennedy,J. S. Petersen, K.N. Houk, and Y. Wu, ibid., tW,7404 (1986). 2 S. Masamune.T. Sato,B. M. Kim, andT. A. Wollman,Am. Soc.,lW,8279 (1986).

gves th rrth HB l1l oI m1 rually-rn bc uscd hrdrond A re& propl d |rnecrI

:ue @ovr olrll-!

chlorophosphite, (CHrO)'PCI (1). This dimethyl ester of phosphorochloridous acid is obtained by reaction of (CH,O)rP with PCl, in [(CHJ2N]rPO as solvent (74.5Vo yield).'

Dimethyl

Z YrE .'LIt L-L Yr

Dimethyl chlorophocphite

ucesncTeases n. and

f (s)-3-:._5-di-

Inositol phosphates.2Phosphorylationof inositol presentscertain difficulties becausethe usualphosphorus(V)phosphorylatingreagentsare relativelyunreactive toward secondaryhydroxyl groups,and phosphatetriester intermediatesare subject to cyclizationand migration to neighboringhydroxyl groups. Thesedifficultiescan be circumventedby phosphitylationwith a phosphorus(Ill) reagentsuchasdimethyl chlorophosphite(1). This phosphiteis more reactivethan a phosphorus(V)reagent, but can still distinguishbetweenaxial and equatorial groups.Thus, reaction of the dibenzoyl-myo-inositol(2) with 1 (3 equiv.) and an amine followed by oxidation

BzO

..oH

lllt*i"

OAc nzo-.2\',o2

3) Hro,

"OBz Ins with f]--j3:1

147

| t

e4%

ZO''

r)HBr, HoAc

2) LioH

| l

.t -Y

).

"OBz

8%

6t 3, Z = PO(OCHr)z

oPo3H2

,oH

"oH

H203PO"

oPo3H2 4 Ithloate, nrr (89-

givesthe tris(dimethylphosphate)3. Cleavageof the phosphatemethyl groups with HBr or BrSi(CH3)3 andesterhydrolysisprovidesthe desired1,4,S-triphosphate (4) of myo-inositol.Exhaustivephosphitylationof 2 is alsopossible,resultingeventually in the 1,2,4,5-tetraphosphate of nyo-inositol.This reactionshowsthat 1 can be used for bisphosphorylationof a crs,vic-diol, and also suggeststhat any free hydroxyl group of a protectedinositol can be convertedto a phosphatemono ester. A relatedprocedurefor phosphorylationof protectedinositolsusesN,N-diisopropyl dibenzyl phosphoroamidite,(BzlO),PN(i-Pr)r,followed by m-chloroper-

o r. and S. Petersen, gtrh t.

o'sPhoro\|,PO as

benzoicacidto form dibenzylphosphates, nO[(Onrt)r, in abour90Zoyield. These

o tl

are convertedto phosphateesters,ROP(OH), in quantitativeyield by hydrogenolysis.3 '2. Mazour,C.A.,U,52758(1977). ' J. L. Meek,F. Davidson, andF. W. Hobbs,Jr.,Am. 9oc.,110, 2317(1988). I K.-L. Yu andB. Fraser-Reid, Tetrahedron Letters,29, 979(1988).

14E

N,N'DimethYlformsmide

Dimethyldioxirane (1), 13, 120' formed by epoxidation of allenes Epixidation of atlenis'l The spirodioxides a r e u n s t a b l e t o a c i d s , a n d o n l y h i n d e r e d o n e s h a v e b e e n o b t a i n e d o n e p of oxidation it90-95Vo yield by epoxidation with peracids.They can be obiained, however' dimethyldioxirane in acetone buffered allenes (even monosubstitutedones) with with solid K2CO3. ExamPle:

562

D'r

t thc t c-atr

E

o

-1. (cH3)2c:c:cHBu H',\A""

' R .I

: s .I

tcu,1,1-8-cHsu

#

nro, f*on

o

il

tl

(cH3)rc-c-cHBu l OH

l OR

+ (CH3)2C-C-QHBu ' t l 85:15 OH OR

'J. K. Crandall andD' J. Batal,J' Org''53' 1338(1988)' N,N-DimethYlformamide' for formylation of tertiary GrigBouveault reaction.t DMF is recommended in 57-6l%oyield by reactionof nard reagents.Thus pivaldehydecan be obtained excessof DMF in ether' i-io,vrrnign"sium chioride with twofold (cHr)3cMgCl + HCON(CH,), #(cH3)3ccHo o{

|,s.Diketones.PotassiumenolatesofsomeketonescandimerizewithincorThis novelreaction give 1'5-diketones' porationof a methylen"g'oup ftot DMF to to the carbonyl group'2 requires a tert-alkylo, pi"nyt group attached ExamPle:

?

ll (CHI)3CCC2H'

t rn

' D

K,THF

(cH.)'NcHo --;'

l.

(cHr)3c

c(cH3)3+ (cH3)3c l:1.44

c(cH3)l

14'{) ln3-Dimethyhlphenylbenzlmidozollne

of allenes oridation idalion of r buffered

lHBu

I

)H

'R. B. Nazarski, (1987). Org. Syn.submitted M. K. Tasz,andR. Showronski, 2S. Kiyooka,T. Yamashita, J. Tashiro,K. Takano,andY. Uchio, TetahedronLetters,tl, 5629(1986). Dimethylhydrazine. cnti-a-Amino alcohols. Organolithium reagentsadd diastereoselectivityto the dimethylhydrazonesof c-alkoxy aldehydesto form adductsthat provide anti a-amino alcoholson hydrogenolysis. Examples: Bzl-_O t l

BzlO :

-

cH3(cHr)4^ZNN(cH3), #

HN(cH3)'

a",(aH,)^f CH,

antilsyn = 97:3 lH,,PrO, IHOAc,CHTOH

Hq cH3(cH,)^aNH' CH, nrarYGrigr!'actionof

OH

l

c.HicHo

OH

-

r

cosS/NH'

: CH,

(92Voee)

: r.r'ithincorlr el reaction

The reactionwas usedfor synthesisof (-)-norpseudoephedrinefrom a chiral can be reversedby o-hydroxyaldehyde(secondexample).The diastereoselectivity addition of alkyllithiumsto o-trityloxy aldehydes,presumablybecausechelation with the oxygenatom is no longerpossible. rD. A. Claremon, Am. Soc.,fm,8265 (1986)' P. K. Lumma,andB. T. Phillips,

fH3 ArN,.

o tl ^c(cHr), l,

1,3-Dimethyl-2-phenylbenzimidazoline(DMBI),1 ll

\-4ry'

>C6H5(1), \

CH,

Preparation.l

Dimethyl sulfoxide-Oxalyl chloride

Dehalogenation.2 DMBI effects dehalogenation of c-halo carbonyl compoundsin a variety of etherealsolventswith formationof DMBITX- in generally itigtr yl"ta. The order of relative reactivity is Br > Cl > F (halides) and primary > secondary> tertiary (for the cr-substitutedposition). In combinationwith HOAc (1 equiv.) the reagentalso reducesacyl chloridesto aldehydes(7O-90Vo yield). (1981)' rJ. C. Craig,N. N. Ekwuribe, C. C. Fu,andK. A. M. Walker,Synthesis,303 : H. Chikashita, (1986). 5400 J. Org.,51' Itoh, H. Ide,andK.

Dimethyl sulfoxideAcetic anhydride. -CHO -->-COOH.I This oxidation can be effected in 75-l00Vo yield by oxidationof the hydrogensulfiteadductof the aldehydewith DMSO-ActO. Esters or amidescan be preparedby quenchingthe oxidationwith an alcoholor an amine rather than water. Example:

CHr

c"trlcHo .-*

:', crH-qHSo3Na I OH

fr,

-

f",

coH5,rso,Na_",o"cpicooH o

lP. G. M. WutsandC. L. Bergh,Tetrahedron (1986)' Letters,27,3995

rA. B. SmrO Letterc,?!l. , 2 D. Kein rr I S. V. Gwb

Dimetly' r Oxihd chloride for prone to gi below. ard ' H . - J .U u r

Dimetlyl r Orid triethylamir ularly in cn are typicall:

I D. F. Tabc Dimethyl sulfoxide-Oxalyl chloride. Severallaboratorieshave reported that Swern oxidation of alcoholscan be accompaniedof c-chlorinationof keto or p-ketoestergroups.Undesiredelectrophilic chlorinationcan be avoidedby useof oxalylchloride(1.05equiv.)and DMSO (2.5 equiv.) in stoichiometricamounts or by use of acetic anhydride or trifluoroacetic anhydridein placeof oxalyl chloride.l Oxidation of amines to imines.t This Swernreagenteffectsoxidation of benzylaminesto the correspondingSchiffbasesin 40-60Voyield. It also oxidizesindofine to indole in 88Voyield. Ring A diosterols.t The ring A diosterols (3 and 4) of triterpenes can be prepared from the Alalkene (1) by osmylation to form the two possiblecrs-diols (2), which on Swernoxidationgive the a-diketone(3). The samediketoneis also obtainedby Swernoxidationof the 2p,3o-diol,the product of peracidoxidation followed by acid cleavage.The diketone 3 rearrangesto the more stablediosphenol (4) in the presenceof base.

Dimetlyl r s-Dh 1 3 6 ; 1 0 l. 6 t cyclic vic

?H ?r R1lcn, 7

I R. Camerlynckand M. Anteunis, Tetahedron,3l, 1837(1975). ' R. L. Funk and G. L. Bolton,Am. \oc.,110, 1290(1988). 3 ldem, TetrahedronLetters,29,llll (1988).

Diphenylboryl trifl uoromethanesulfonate. Asymmetic esterification. meso-Cyclohexanedicarboxylic anhydride (1) undergoes a highly stereoselectiveesterification with the diphenylboric ester (2) of (R)-2-methoxy-1-phenylethanol in the presenceof diphenylboryl triflate to provide,

Dipfcryl Rd of alkenq (C'H.S), r stereosck vrnylcydo

*v

R = R ' =

Diphenyl diculfde

155

after reaction with diazomethane,the optically active ester 3.' The asymmetric esterificationcan be usedto resolveracemic1. Thus dl-l(2 equiv.) reactswith.2 in the presenceof the triflate to give, after esterification with diazomethane, ,t\.'CH'

?"(t'l*-,)(c"H,):Borr /vcoocH' .l zriH-'r' , | ** \Aco'>7cH'ot"' 2

)H

+ c.H|/ocH3

) *rth sec-Buli (3) as ,-r-droxin der reactionto

CoH, (lS,2R)-3, (99Vode')

* 2

CH. + HCHO

l) (c"H.)rBoTf.(f 2) cH'N, , 737o

CuHt

dl'l

(tR,2R)-3,c6 - 87.6.(9ovode)

(1R,2R)-3 in %)Vode.2Evidently, the (1R,2R)-enantiomerof I is esterifiedin preferenceto the (1S,2S)-enantiomer. ' M. OhshimaandT. Mukaiyama,Chem.Leners,377(1987). ' M. Ohshima, ibid.,1233(1987). N. Miyoshi,andT. Mukaiyama,

it n resultsin a t - 1 . 1 . - 3 - t r i(o6l) . hrJrolyzedto a

Diphenyl disulfide. Radical 13 + 2lcycloaddition.t Cyclopentanescan be prepared by addition of alkenesacrossvinylcyclopropanescatalyzedby phenylthio radicalsformed from (C6H5S),and AIBN. A Lewis acid suchas AI(CH3). can increasethe rate and the stereoselectivity of this radicalinitiatedcycloaddition.Thus the combinationof the vinylcyclopropyl ester I with /-butyl acrylate (2) provides the four possiblecyclo-

* "O (c"ll'?nrBN' R-

'7

.cH:cH2+

ciltr:611p'

*

a*'

2

crs-3

I R=R'=CooC(CHr)r + Al(CHr)3

o"t'

3:l 6:1

53Vo 52Vo

n' ftfcH, : .rnhydride(1) tr,nc ester(2) of itl.rteto provide,

\]

tR' trans-3

156

S-(-)-2-(Diphenylhydroxymethyl)pynolidine

pentaneswith somepreferencefo, tfr. crs-adducts. This crs-selectivity is enhanced presence by the of a Lewis acid. ' K. S.Feldman, 3300 Jr.,andR. F. Miller,Am. Soc.,110, A. L. Romanelli, R. E. Ruckle, (1988). S-(- )-2-(Diphenylhydroxymethyl)pynolidine[(S)-Diphenylprolinol], 1, m.p. 75o, cp - 68.1o.The reagentis preparedby reactionof CuH,MgClwith the N-Cbz derivativeof (S)-prolinemethyl ester. Enantioselectivereduction of ketones.r The 1: 1 complex 2 can be isolated from the reactionof l with BH3'THF (3 equiv.).It forms anothercomplex(3) with A complexsimilar to 2 BH, in solution,which can be identifiedspectroscopically.

A n

\NAc(c^H,), H

| OH

BH,.THF

" -+

N=B'

FDI availid

w

than d produ the all

'H. Dl

2,3Di

}J to fon (3) in I be coo

o

s

(s)-r (S)-2,m.p. 107-124"

Hr'

)

and identifiedas an is also formed on reactionof BH. with (S)-diphenylvalinol, intermediatein the asymmetricreductionsof that amino alcoholwith BHr. Simireduclarly, complex2 in combinationwith BH. can effecthighlyenantioselective tion of ketones, but 2 can function catalytically.Thus optimum asymmetric reductionis effectedwith 0.6 equiv. of BH. and 0.05equiv. of (S)-2in THF at 25', observedso far for reductionseffectedwith and is the highestenantioselectivity LiAlH4 or BH. in combinationwith a chiral amino alcohol.Typicalenantioselectivities are shownfor someof the alcoholsobtainedby this procedure. OH

I

C6H5CHCH3

c6H5cHc2H5

OH

OH

(R),97Voee

(R),90Voee

(cH3)3ccHCH3 OH (R), 887oee

t

i

l

t

\--'\v'l

A, P-

(R), 897oee

Chemicalyields in all casesare )99.7Vo, and the reductionsare completein about 1 minute. The paper includesa rationalexplanationfor asymmetricreductions with complex3. '8. J. Corey,R. K. Bakshi, (1987). Am. Soc.,109,5551 andS. Shibata,

l-IDl

tt crrldE doctr on re5

1,S7

l,3'Dithiane

enhanced , 110.3300

m p. 75o, he N-Cbz e r:olated r r r 3 )w i t h r m r l atro 2

t. :^H.

(1). The ester is p-Diphenylphosphinopropanoicacid' (C6H5)TPCHTCH,COOH availablefrom Strem. Wittig reagents.t Wittig reagentspreparedfrom 1 show higher (E)-selectivity Moreoverthe bythan the correspondingonespreparedfrom triphenylphosphine. separatedfrom water and readily is solublein product,(C6H5)rP(O)CHTCHTCOOH, the alkene. ' H. DanielandM. LrCorre,Tetrahedron Letters, S, 1165(1987).

2,3-Diphenylsulfonyl-1,3-butadiene. SPynolines.t This dieneundergoesa [4 + l]annelationwith primaryamines to form a pyrrolidine 2 that can be convertedto a 3-(3-phenylsulfonyl)pyrroline (3) in high yield. Thesepyrrolinesare oxidizedby DDQ to pyrroles(4), which can pyrroles(5). be convertedreadily to 2,3-disubstituted

so2c6H5

c"Hrsor. ,so2c6H5 ' NaOCH. ,-< + / / \ -qtq

cH,cr,. nzcr'---r'c ' + RNH2 cH'oH iticd as an Bll, SimiIrrc reduclsr mmetric JIF at 25', lected with ranIioselec-

so2c6Hs

-> I

/

\N/ R

\*2 R

\

3

2

,-n,o, ooo f

/1

,SO,C^H.

(*A*'

l) rBuLi

.2tR't ffi-e\qa

,SO,C^H. _J

fl

\\

\*/

R

R OH

/so2c6H. \

5

rA. Padwa (1988). andB. H. Norman,Tetrahedron Letters,29,304l

r, Cc

crrmplete in rtnc reduc-

1,3-Dithiane. ring systemsfrom a Ring enlargement.r A new route to seven-membered (1) of ethyleneto provide the bicycyclohexenone involvesa photocycloaddition clooctanone2. Addition of lithio-1,3-dithianeto 2 providesthe adduct3, which on reactionwith HgO and HBF. forms an unstablerearrangedhydroxy aldehyde

15E

l'3-Dithiane

(a) that undergoesretroaldol cleavageto a cycloheptanederivative that is oxidized to the dicarboxylicacid 4.

o ,\

(A

+CH2:CH,

HgO, HBFr. THF +

-\

CH,

LA]*p a

I B. C. Ranu and D. C. Sarkar,./.C'S. Chem. Comm',245 (1988)'

Ephedrine. Enantiot action hash (2-chloroeth pratesobtai

then with u alkylcycloh ically depen basisof the ,

CH,

CH

z (

Enantia preparedthc rine and rq enantios€l€ can be conve complexsud of I, sho* tl bv the chira

rl r! oxidized

H g O .H B F { , THF +

Ephedrine. Enantioselective conjugate addition of cuprutes. This enantioselectivereaction has been demonstratedusingthe amino alcohol1, preparedby reactionof (2-chloroethyl)dimethylamine with(1R,2S)-(-)ephedrine,as a ligand.' The cupratesobtainedfrom 1 by deprotonation(RLi), reactionwith CuI.S(CH.)2,and

QH' : CoHt:-Ap,,\_.,N(CH.),

COOH

: oH

l cH'' l, cp + 1.86'

CH, then with an additionalequivalentof RLi, add to cyclohexenone to give (R)-3alkylcyclohexanones (2) in 85-927oee with recoveryof 1. Optical yieldsare critically dependenton the purity of RLi. The enantioselectivity is explainedon the basisof the cupratemodel A.

H

-

(-\Fcun t t -

Yo_r, (2) A

Enantioselectiveaddition of RrZn to aldehydes. Corey and Hannon2have preparedthe diaminobenzylicalcoholI from (S)-prolineand (1S,2R)-(+ )-ephedrine and report that the chelated lithium salt of I is an efiectivecatalystfor enantioselective additionof diethylzincto aromaticaldehydes.Thus benzaldehyde canbe convertedinto (S)-(- )-3 with95Voee,via an intermediatetridentatelithium complexsuchas2 formedfrom 1. Similarreactions,but catalyzedby diastereomers of 1, show that the chirality of addition of dialkylzincsto aldehydesis controlled by the chirality of the benzylicalcoholcenterof 1.

iodide (Ethoxycarbonyliodomethyl)triphenylphosphonium

.H

I cH3

T t'-d-

cH,, d (-ll

Ho 1

*o'

, HO'-.s.."H coHr-\crH,

-.2n,,, crH, c,H,

3 (95Voee)

I J. Chenau

Ethyl 2"ln by bromiu Vinylq c,p-enon a bicyclict

c.Hi"\H ,,

The same laboratory has preparedthree tridentate zinc chelatesfrom chiral addition of tertiary amino phenolic alcoholsand used them for enantioselective ee. Resultswith the ligand4 [from (1S,2S)diethylzincto aryl aldehydesinT0-877o ( + )-pseudoephedrine] are typical.

t-nu1,\

\4""

9H.?H. flA-.

'c'u5

oH

t)v 2)rc

(r)(t

This[3 pentalene

zn(c,H.),,

cH. r

t-Bu

CH;\

/-Bu 5

3 (81'ZVo ee)

rE. J. Corey,R. Naef,and F. J. Hannon,Am. Soc.,f0E' 7114(1986). r E. J. Corey and F. J. Hannon, TetrahedronLetters,!E, 5233,5237(1987)'

iodide' (Ethoxycarbonyliodomethyl)triphenylphosphonium (1). The saltis preparedby iodinationof a two-phase (C6H5)3P+-CHICOOCTH5Ibromide systemof solid K2CO3and (ethoxycarbonylmethyl)triphenylphosphonium in CH3OH; m.p. 1.51',80Voyield. Propiolic acids.t The ylide derived from 1 convertsaldehydesinto propiolic estersor the acids in 50-70Voyield.

Etlryl 2.bromocrotonete

I

r) K,co.cH'oH I

I tiiibHo

I .H.

16l

zI I *,Fo', , | *c"-c Rc:ccooqH, ## -aoocrH5jI Rc-ccooH L

I J. Chenault (1987). andJ.-F.E. Dupin,Synthesis,498 Ethyl 2-bromocrotonate,CH3CH:C(Br)COOCTH5 (1). The reagent is prepared by bromination of ethyl crotonate followed by dehydrobrominationwith DBU' Vinylcyclopropanation; cyclopcntenes. The lithium dienolate of I adds to a,p-enonesto form an c-keto vinylcyclopropane,which on pyrolysis(550') provides a bicyclicketo acrylate(equationI).'

t l r al nof

:s)cooc2Hs

(60:40)

annelationhasbeenusedto obtainthe sesquiterpene This [3 + 2]cyclopentene pentalenene(6) from the enone2.2Reactionof 2 with the dienolateI providesthe

T CHr-

cH,\-v-o?

-

r. LDA

H C,H'

CH, CH,

CH, CH,

CHOCH"

CH, CHr

cHocH3

r. ce)

'phase omtde oproltc

CH, CH,

'CH,

S€vcral Stc96

c2H5ooc

16i2

Ethyl (S)-3-hydroxybutanoate

expectedadduct3. Pyrolysisof 3 doesnot result in the expectedtricyclic cyclopentene,but the derivative4 undergoesthe expectedcleavageto provide the triquinane(5), which is a usefulprecursorto 6. lT. Hudficky, H. Luna,F. E' Anderson,lll,J'Org',51'4'146(1986)' L. Radesca, ' T. Hudlicky,M. G. Natchus, ibid.,52,4641(1987)' G' Sinai-Zingde, CH"

I D. Sa(

il-

Ethyl c-(bromomethyl)acrylate, BrCHzeCOOqH5 (1). a-Methylene-7-lactams.r The Reformatsky zinc reagent derived from this acrylatereactswith iminesto form c-methylene-1-lactams. Example: CH,

| + zn

rHF, t'-",

fit' BrzncnrtcoocrHr #5

r
70Vo. (MEM) ethers Convenionof MEM ethercto esters.42-Methoxyethoxymethyl in are convertedinto carboxylicestersby reactionwith an anhydride the presence of FeCl: (0.4 equiv.) (equationI). Selectivecleavageis possiblein the presenceof a benzylether but not in the presenceof a t-butylether.Aromatic rings,if present, can undergoacylation. (D

+ (CH3CO)'O ROCHTO(CH2)2OCH3 #

ROCOCH3

lurr. ) Permits etrselectivitY. d rn Al,O3or

I L. F. TietzeandU. Beifuss,Synthesis,359 (1988). 2S. E. Denmark (1988). andR. C. Klix, Tetahedron..l4,4(X3 3M. H. Park.R. Takeda.andK. Nakanishi, (1987). Letters,2E,3823 Tetrahedron I R. S. GrossandD. S. Watt,Syn.Comm.,l7,1749(1987).

crtendedthe near tricycles lemperatures, The reactions

Ferrocenylphosphines,chiral, Ll., 237-240. Asymmetricaldol reaction.t In the presenceof a gold(I) complex(1) and a (2), variousaldehydes reactwith methylisocyanoacetate chiralferrocenylphosphine

16

FerrocenylPhosPhines

(4) with high enantio-and diaster(3) to form 5-alkyl-2-oxazoline-4-carboxylates eoselectivity.ExamPle:

fc

al

(t

CH.

t

[Au(c-HexNC)r].BF4-

(1)

cHGrcH2N(crHs)2

/:,

(2)

()[-rtcuH';'

cH3cHo + cNcH2coocH3

l,2, cHrcl2,25'

cH,.... ,coocHl

r\

o-.1*

lNVo

3

-,

cHr... ...coocH3 iF-R'i r l \

84:16

o-.l* cis4 (44Vo ee)

tans-4 (72Voee)

s! fo ]l

tc

resultsin the trarr-adductexThe samereactionbut with trimethylacetaldehyde gold catalystis essentialfor of the clusivelyinl[}|qo yield and in977o ee. The use lesseffective.The length much the high selectivity;silver and coppercatalystsare ferrocenenucleusis also the and of the sidechainbetweenthe diethylaminogroup an important factor in the selectivity. Asymmerrichydrogenationoforp-unsaturatedacids'22-Aryl-3-methyl-2-buhydrogenationcatalyzedby a comtenoicacids(2) undergohighly stereoselective (r)' but not with plex of rhodium with the chiral (aminoalkyl)ferrocenylphosphine

H... /cHr

r)cH:cH'\_-/ tr*1 i-ii :H ('" f--p(C^H,), .hP(cnH.),

(R)-(s)-l

cH,'.-a-cH'

CH(CH1),

H: (R)-(S)-tlRh

tl

A

or,'L1'.cooH -H

A.-c-cooH ee) (S)-3(97-98.474

) CrH,--a,,,CH,

c n,jcH,

l l coHic-coor-r

c,Hi\cooH

n

Cl

s I.

(2s,3s)-s(97okde)

9{l

Th rid

N-Fluorotrifl uoromethylsulfonimide

rl ritster-

lacking the terminal alkylaminoside chain. This hydrogenferrocenylphosphines ation also provides accessto acids with two vicinal chiral carbon atoms such as

(2s,3S)-s. 'T. Hayashi, andT. Hayashi,.4n' Y. Ito, M. Sawamura' PureAppt.Chem.,&,7(1988); (1986). Soc.,10E,6405 2T. Hayashi, (1987). andY. Ito, ibid.,109,7876 N. Kawamura,

coocH3

a ee I

d'luct exrntral for }lc length eu. l\ also rhr l-l-bub,\ .r comIt :()t \A'ith

Fluorine. Dlectrophilic substitution,t Tertiary carbon atoms can undergo electrophilic substitutionwhen treatedin CFCI./CHCI,with dilute F, in nitrogen.The chloroform acts as a radical scavengerand stabilizerfor F-. The substitutionproceeds with retention. The reaction showssome regioselectivity.Although t has three tertiary hydrogens,the major productof fluorinationis 2. CH,

CH.

A , , , 4 '*

YoaocuHnNo, cH(cH3)2 1

Yoaoc6H4Noz

(cHr)rcF

, BFl.o(c'H')' I

?'' ^

t

l

fococ6H4NO2

crri\H, 3 when treatedwith BF. etherateor Theseproductsundergodehydrofluorination CH3MgI. I S. RozenandC. Gal,J. Org.,52,2769 (1987). N-Fluorotrifluoromethylsulfonimide, (CF.SOr)rNF (1). The imide is obtained in 95Voyieldby reaction(CF.SOr)rNHwith F at - 196'with gradualwarmingto 22o. The imide is stableat22',but shouldbe storedin a fluoropolymerplasticcontainer rather than slass.

16E

FormeldehYde

TheN-fluoroimideeffectsdirectaromaticfluorinationat22"'withhighprefIt also converts NaC(CH3)erence for ortfto-substitution of substituted arenes. yield'l (COOC,H.), into FC(CH)(COOCTH5),in 967o

(

rS. Singh,D. D. DesMarteau, S. S. Zuberi,M. Witz,andH.-N' Huang'Am' soc"l:09' 7t94(1987).

Formaldehyde. synthesisof piperidines Pipefidines, Grieco et al't have describeda general allylsilaneand 2 equiv' of by reactionof the acid salt of a primary aminewith an of iminium ion (a)' derived formaldehydein water.The reactioninvolvesreaction fromtheamineandtbrmaldehyde,withtheallylsilanetoformahomoallylamine with captureof water (b), which cantbrm a secondiminium ion (c)' which cyclizes to the piPeridine.

(I) BzlNHz'TFA

I

tn'o, gztfrH:cH,'6occF. I (")

(CHJ.SiCH:CH:CH:

,

|

L Bzl

BzINH

TFA. CH:o

I

(CH2)2CH:CH2 (b)

I /*o.t, I \-'-r'ctt' (c)

Thisreactionwasusedtoeffectapolyolefincyclizationinasynthesisofthe of 1 with HCHO alkaloid yohimbone(3)'' Thus reactionof the trifluoroacetate providesa63Voyieldof2,whichwasconvertedinto3byasix-stepsequence(107o overall yield).

ln ri

Formrldehyde

ugh prefaCtCH.)I) TFA

. Soc..\\D,

1)RCRO

b s\eps ----+

639o

of piperidines nd I equiv. of n rr). derived om0allylamine iplure of water

cH2S(CH3)3

CHt

Aminomethano destannyration; bishomoaryr amines.

Methyreneimmonium ';r,i*l"#r'JH? am i n e s . " d il[":ili,* r; ;,i1Til :rrur d;;yd e.reac r #, .u rurm otsttomoallylic ro,;;r aminesin high yield:

Example:

t".o:ffA I

iT"' rthesisof the ,*rth HCHO q u e n c e( 1 0 %

cH.O'.\-,/

HcHo.rFA

ll

I

Nu,.rne

l;"

CH,OH.cHct, -------------_*

ooccn

lm

fformylmethyl)triphenylrrsonium

bromkle

The reaction can effect cyclizationof the side chain of tryptamine (1) to form a substitutedpiperidine ring (2)'3

I

ll

ll

\A*/

llff8fi3:*

---Bu,sncH,cH:cH! NH,'rFA n%I

Grignlra Mot reactswil

H

clsi(cH

(cH.):c

COOH 2 I S. D. Larsen,P. A. Grieco,andW. F. Fobare,Am' Soc''10t' 3512(1986)' 2P. A. GriecoandW. F. Fobare, l.C.S. Chem'Comm',185(1987)' r P.A. GriecoandA. Bahsas,l.Org.,52,1378(1987)' (Formylmethyl)triphenylarsonium bromide (1)' The salt is prepared from m.p. 161",yield,90%' (C6H.).Asand bromoacetaldehyde; (ErZl-lr3'Dienes.tThisunit,oftenpresentininsectpheromones'canbe provide obtained with high stereoselectivityby reaction of an aldehydewith 1 to with BuLi generated phosphorane an (E)-c,p-enal (2), which on reactionwith a and HMPT provides(E,Z)-dienesalmostexclusively' Bt, CH3(CH2)?CHO+ (C6H5)3AsCH2CHO*/ 1 I)THF,HMFr

2 + (c5Hs)3p:cH(cHz)oot%;-

reactionf and LDA suchas 2.

.U

CH,(CH2)7CH:CHCHo 2(E>987o)

"- -' ---;)a:a1..'r:-"a(cH2),oH N/H

,H3(CH2)?\^

'"-H 32,5E,94Vo)

I Y.-2. Huang,L. Shi'J' Yang,andZ' Cai'l'Org'' 52' 3558(1987)'

coq Grignan erateyk

lo form

Grignard reagents. Monoaddition to esters. The reagentformed from RMgX and LDA (1:l) reactswith estersor amidesto give enolatesof ketones,which can be trappedby of artemisiaketone(l) bv an aldol ClSi(CH.)..rThis techniqueprovidesa synthesis

H:CH:

o tt

[

r )LL D Ai |

Q- l

A

I

l

@ (cH,),cHfoc,Fr, | ."ffoC:H. 'CH. CH; L

oH

?

culYs.". 'cH.

ft'

9

" ' l"t4-"tt'

|

--+#-

J

r)Ac.o. Pv B jil{"" *cr'$ca, {r r

cH{

?"'

'cHl

cH;

I red from s. cen be o provide rith BuLi

chloride reactionfollowedby reactionof the estergroupwith methallylmagnesium and LDA. Actually Grignard addition/alkylationcan provide complex ketones suchas 2.

-1 ? *.X)"r'' fli ft' LpAfcH'rrcn' cocH3

,l

cH, (cHr)roH 'H

L

an 9.",

.",

l=f-r!

I

=cH, CH,CH:CH, 2(1:1)

Coupling of RMgX with dithioacetals.2 In the presenceof ClrNi[P(CoH,)Jr, alkenesin modto give cross-coupled Grignardreagentsreactwith 1,3-dithiolanes erate yield. t7r

tl2

Grignard resgents

Example:

,:x

t i l +l CHTMgI ;7 V,\-/

andR. Perret,jbjd., 'C. FehrandJ. Galindo, (1986); C. Fehr,J. Galindo, He\v.,69,228 70, r74s(1987). (1987)' ' Z.-J.Ni andT.-Y.Luh,J.C'S.Chem.Comm',1515

N-lt A NBS br-rq El

G T llar

t

porro crck Thrr pred !lgc1

Ptrret, ibid.,

N-HalosuccinimideSodium ethoxide. Halodeacylation.t Reactionof a B-ketoester or a p-diketonewith NCS or NBS and a base(alkoxideor KOH) resultsin an c-halo esteror an ct-haloketone by replacementof an acyl group by halogen. Example:

o

CI

tl

I

NCS, C,H5ONa,

(cH3)rcHcHccH3 I

#(cH3),cH

cHCOOC2H5

cooc2Hs rG. Mignani,D. Morel,andF. Grass,Tetrahedron Leuers.E'5505(1987). Hexabutylditin,(Bu.Sn)2. Iodine-transfer cycliZation. Irradiation of unsaturatedc-iodo carbonyl compoundsin the presenceof a hexaalkylditin(5-l0Va) can resultin isomerizationto cyclic1-iodo carbonyls.'The reactionis very slow in the absenceof an initiator. Thus under these conditions1 isomerizesto a mixture of 2 and 3 in which 2 predominates.The reactionis particularlyuseful for formation of fused bicyclic systems(4 + 5).

y'CH,

t-BuO

(Bursn),. /ru.8ff

|

\rcH'r

J o /-.

I

ESVo

(/ 4

COO+-Bu

COO+-Bu

+(

-r)

\y',

174

2,3,4,5,6,6Hexochloro'2,4-cyclohexadiene'1'one

Sunlamp irradiation of butynyl iodide (6) in the presenceof hexabutylditin generatesan alkyl radical that reactswith an electron-deficientalkene (7) to form (8) in moderateyield.This productcanbe reduced an (iodomethylene)cyclopentene (9)'' by Bu3SnH(AIBN) to the methylenecyclopentane

gcoocH3 . [:oo"'jry' i: 5-"*lJ, t (E/Z= 3:l)

in bo

r P

(l

rl lh

ral

jut uti 8r(

527o I BurSnH ovcrallI AIBN

CHt

stt th slc

(A,-coocH3

\J

str 9

I D. P. Curran and C.-T. Chang,Tetrahedron Letters'2t'2477 (1987)' 2 D. P. Curran and M.-H. Chen,Am. Soc., 109,6558(1987)' 2,3 r4,516r6-Hexachloro'2,4'cyclohexadiene'1'one (1)' lf ' 25 1' Dehydrogenation.|Thetetrahydro-p-carboline2canbedehydrogenateddieffected rectly to the dihydro-p-carboline 4 by two equiv. of 1, but the conversion is

'cHloH,[.",,o3] ct 3 80% rFA I

o

v

(l

n

r} al .d l3l

Hexamethyldisilezane-Chlorotrimethylsilene

175

bun lditin It to form c reduced

in higheryield by a two-stepreaction,asshown.Osmylationof the isolateddouble bond of 4 furnishesa diol, which is a known mycotoxinof somefungi.

)ocH3

Hexa-p-hydrohexakis(triphenylphosphine) hexacopper hexameric], [hydrido(triphenylphosphine)copper(I), [(CuHr).PCuH]o(1). Preparation by reactionof [P(CuHr).CuCl]o with sodiumtrimethoxyborohydride.' Conjugate reduction,z This stable copper(I) hydride cluster can effect conjugate hydride addition to o,B-unsaturatedcarbonyl compounds,with apparent utilizationof all six hydride equivalentsper cluster.No 1,2-reductionof carbonyl groupsor reductionof isolateddoublebondsis observed.Undesirablesidereactions suchas aldol condensationcan be suppressed by addition of water. Reactionsin the presenceof chlorotrimethylsilane result in silyl enol ethers.The reductionis stereoselective, resultingin hydride deliveryto the less-hindered face of the substrate. Examples:

'P. H. H. Hermkens, R. Plate,andH. C. J. Ottenheijm, Tetrahedron Letters,29,7323 (1e88).

ot l

o

-A-

ll t

pnated di-

t

|

l

A

--l.c"H".H?o ,r%-

+

cH,\

CH_CH.

cHl 100:1

r<effected

o ll CH.O

c.Hs'Act, o cHs-AocH2c6Hs

osi(cHr)l

l9#{

cus}.Acu, o

L'"' a"a\AocH2c6H5

rM. R. Churchill, S. A. Bezman, J. A. Osborn, andJ. Wormald, Inorg.Chem..ll, l8l8 (r972' t. ' W. S. Mahoney, D. M. Brestensky, andJ. M. Stryker, Am. Soc..ff0,291(1988). HexamethyldisilazaneChlorotrimethylsilane. Selectivesilylation. Hexamethyldisilazane alonecaneffectsilylation,but only at elevatedtemperatures.Rapid silylationof amines,alcohols,and acidscan be achievedat 0oin CHrCl2if chlorotrimethylsilane is alsopresent.Selectivesilylation is also possibleby adjustmentof the proportions of HMDS and TMSCI. Thus only

176

Hydrogenperoxide-Benzeneseleninicecid

(1 equiv') and TMSCI the amino group of amino alcoholsis silylatedby HMDS primary alcohols'but of silylation (0.1 equiv.). The same ratio effectsselective Finallytertiary reagent' each of ,""onOuryalcoholsaresilylatedby useof 1'3 equiv' DMAP as with together reagent each alcoholsare silylatedby useof 2'5 equiv' of catalyst. rJ. CossyandP. Pale'Tetrahedron Letters,8,6039(1987)' Hexamethylphosphorictriamide (HMPT)' Michaelgdditionsofketoneenolates.|ThestereochemistryofMichaeladby the geometry ditionsof lithium enolatesof ketonesto c,B-enonesis controlled oftheenolate.Additionof(Z)-enolatesresultsinanrj-productswithhighdiasterReactionof (E)-enolates eoselectivity,which is not changedby additionof HMPT' which can be enhancedby is lessstereoselectivebut tends-tofavor syn-selectivity, additionof HMPT. lD.A.OareandC.H.Heathcock,TetrahedronLetters,T|,6169(1986).

Hyir

o -0.5

largetainiq but ar peror] which efiect l,+bc

' D. \'. Hydrr

a

troncs is app in 1.1 E:u

Hydrogen Peroxide. " can be usedto convert cilovig" of si_.c bonds(12,243_245). This oxidation Thus Grignard reagentscleave vinylsilanesin three stepsto,yn- o' anti-7,2-diols' which can.be oxidized epoxidesof vinylsilanesseteciinelyto p-hydroxy silanes' to an (E)-vinylsilane' with retention of configurationto 1,2-diols.when applied is obtainedfrom a (Z)the sequenceresultsin the syn-l,2-diol; the anti-l,2.diol vinylsilaneby the samereactions' $iR,

(r) *''.,)

--

Rr : Me:(O-iPr)

$iR,

Ru

-O

R,MgX (cucN)' R'\ln'

?'*,

I OH

- H:o,. KF; KHCOr 45-75co overall

OH

R:ln' I OH (anti)

Tlx to oxi
95Vo de.

tso dLl eny I

I D. Seebach Helv.,69'1147(1986)' andJ. Zimmermann,

o tl

C6H5I-OP(OC6H5)2(1)' [Hydroxy(bisphenoxyphosphoryloxy)iodolbenzene, OH

PrC

IHydroxy(tosyloxy)iodolbenzene

3t the ctt ftrllowed l cleavage

This iodine (III) reagentis obtainedin 90voyield by reactionof cuH,I(oAc), with diphenylphosphate,(C6H5O)rPOrH, in aqueousCH.CN. Phosphorylation of ketones.t Ketones bearing an adjacent methylenegroup reactdirectlywith I to form cr-ketolphosphates in60-B0voyield. The reagentalso efiectscyclizationof 4-pentenoicacid to a phosphorylatedlactone.

o cH3CoCH3* 1 aictal lacde in rldehy ct cnantioacrd.Thus,

o Ao n t,

cH,:6116112CH2cooH * I +1,,-

I G. F. Koser,J. S. Lodaya, D. G. Ray,III.

cH,Jcn,o$(oC6H5), + C6H5I

1cuH,o;r$o-

lro:oo \J

(l9gg). andp. B. Kokil,Am. ioc.,1f0,29g7

[Hydroxy(tosyloxy)iodo]benzene, C.H,I(OH)OTs (t), m.p. 135-138.. This trivalent iodine compoundis obtainedin about 90% yield by reactionof CoHrI(OAc),with toluenesulfonicacid (2 equiv.) in CH.CN.r lr3-Enynes. The reagentaddsto terminal alkynesto form alkynylphenyliodonium tosylates(2) in moderateyield (equationI)., Thesesaltscouple with alkenylcopperreagentsin etherto give I ,3-enynes, with >99voretentionof the alkene R'C:CH

+ I

R' = CHr R' = t-Bu, CoHs

cH' crr'25') [C6H5IC-CR,]rOTsl9%o fi-7|Vo

geometry.Sincethe alkenylcopperreagentsare formedby syn-additionto terminal alkynes,the couplingreactionprovidesa new route to pure 1,1-disubstituted 1,3enyneswith control of the alkenegeometry.j Examples:

PrkCH+BuCu-J">.:.t:t98Vo ee)

c

: H

(-)-Menthyl(S)-ptolueneculfinete

ms

l i t r o n( 7 : l ) i s d d u c r .( + ) 4 , ler.rndisol(6) rt',-1-JP1o-

ketal is effectedby reaction with the enol silyr ether of acetophenonecatalyzedby Ticla; after protection of.the resulting hydroxyl group, the chiral auxiliary is removed with potassiumt-butoxide to give 4 in >9gvo ee. The overarrresurt is enantioselective difierentiationof the hydroxymethyrgroups in 2-arkyr-l,3-propanediols.

llr*ithaprodl.r\tereOmerS h r d r o l y z e dt o

' M. Demuth, palomer,,H_D. A. Sluma,A. K. Dey,C. Kruger,andy.-H. Tsay,Angew. Chem.Int. Ed.,25,1117 (1986). ' T. Harada, H. Kurokawa, andA. Oku, Tetrahedron Letters,g,4g43,4&l7 (lgg7). 3T' Harada,T. Havashiva, I. wada,N. i*;-.1;,;; A. oku, Am. soc.,r09, s27(1g87,t.

R

fl

( - )-Menthyt (S)-p.rotuenesutf nare, (t). ;f,-Orr,r"rrhyl

Esterificationof p-toluenesurfinic acid with ( - )-mentholgivesa mixtureof two .. diastereomers,which equilibrateto the pure (-)-menttrytls;p-roru"*surfinate diastereomerin the presenceofhydrochroric acid (g|va yierd).Thereport incrudes an improvedprocedurefor reactionof I with CH.MgI to give (R)_(+ )_methylp_ tolyl sulfoxide.'

HO'

Y"

p

OH .2

I'Alkenyl p-tolyl sulfoxidcs.2 Various l-alkynylmagnesium bromides react stereospecificalry (with inversion)with I in ether/toruene to give chirat l_arkynyl sulfoxides2. Reductionof 2 with LiAlH. (THR _90) afiordsopticallypure (E)_ l-alkenyl p-tolyr sulfoxides(3). The corresponding (Z)-isomers'areouiaineo by hydrogenationof 2 with the Wilkinsoncatalvst.

-i-Jrrrlsto (R)e ,lrwith the tc more stable nl hondof the

RC:cMgBr #Rc-c["-'\ir, # Ed 2 I eo-%%JHr, er.

fl

d\r", (E)-3

o

R. ^oc(cuHr), l. $n ee)

gi

'e.,[t, E/ (z)-3

I G. Solladid, J. Hutt, and A. Girardin, Synthesb,173 (lgg7). 2 H. Kosugi, M. Kitaoka, K. Tagami,e. iaUf.^i,i ind H. Uda, J. Org.,52, l07S (1987).

M

MercurY(II)oxide-Iodine

Mercury(Il) oxide-Iodine' obtained of lactols' Medium-sizedlactonescanbe Lactonesby ring expansfon inreasonableyieldbyptrotolysisofthehypoioditesofcatacondensedlactols,which are available The substrates -forottne UriOglngbond' resultsin regioselective.f"uuug" to the 10cleaved is which 1' lactol the 6/6 by the general route shown be used for preparationof 9-membered memberedlactone2. This cleavagecan oc2H5

**e

6

-= O5 &t*')'olHcs'

8/5 fused ll-membered lactonesfrom 7/6 or lactonesfrom 6/5 fusedlactolsand of cleavage this is cleavedpreferentiallybecause lactols.In all cases,tt'" UtiAgingUond resultsin the most substitutedradical'' T h i s h y p o i o d i t e r e a c t i o n c a n a l s o b e u s e d f o r r i n g e x p a n(3) s i ofurnishes n o f c y c l i cthe ketones.2 Thus Barbier "y"tirution oi o-1'-ioOop'opyl)cyclododecanone iodo cleavageto a l5-membered bicyclicalcohol4, whictrunde'go"""gio'"iective

o

Ar..),r

(

)

e

\1.t,['

liilll 4

%

l) HgO/lr 2) hv Vo

ketoa BuSt

rH.s 2 ldcr

pMc Prt

cH'(

, tiary read can I recq

r A .I

Mct I pars thc I phct gtql

8rw

3

l(l

T !

Methoxy(phenylthio)methyllithium

btained r .* h i c h r ailable thc 10mbered

) .)

?ns

ketone (5). The final step to exaltone (6) involvesa free radical reductionwith Bu.SnH. I H. Suginome 43,3371(1987). andS. Yamada,Tetrahedron, 2ldem, Tetrahedron (1987). Letters,2E,3963 p-Methoxybenzylchloromethyl ether (1). Preparation:

cHro4 "

\-crtroNu

crcH'scHr) cH3o-c6,H4-cH2ocH2scH, I

\:/

.",oOcH2ocH2cl I

)

t : fused ,c l c a v a g e | i ct ( ) n e s . r r t . h c st h e e rc.l iodo

Protection ol alcohols.r Even somewhathindered secondaryalcoholsor ter(PMBM) ethersby tiary alcoholsare convertedinto (p-methoxybenzyloxy)methyl in CHrCl, for 3-30 hours.Deprotection reactionwith 1 and diisopropylethylamine can be efiectedby oxidation with DDQ (65-95Voyield), a method previously recommendedfor deprotection of p-methoxybenzylethers (11, 166-167) I A. P. Kozikowski Letters,2E, 5125(1987). andJ.-P.W't, Tetrahedron Methoxy(phenylthio)methyllithium (1), 6, 369. (2), preHomoallyl ethers or sulfides.t gem-Methoxy(phenylthio)alkanes pared by reactionof I with alkyl halides,react with allyltributyltincompoundsin the presenceof a Lewis acid to form either homoallylmethyl ethersor homoallyl phenylsulfides.Use of BF, etherateresultsin selectivecleavageof the phenylthio group to provide homoallylethers,whereasTiCloeffectscleavageof the methoxy group with formation of homoallylsulfides.

?'",

*f"

?cH, t *a'.AcH,

* CH2:QHQH2SnBu3 -

SC,H,

+

icuH, l n\AcH,

3

2 (R = n-C6H1) BF3'O(CrH5)2 Ticln

7ZVo 79Vo

4 100:0 6:94

TetrahedronLetters,8, 6299(1987\.

Methyhluminum bis(2'6di-tnutyl'&methylphenoxide)

A subo the a seleo

?t'"'

(cH3)3sitli (1)' ocH3

with I in the Reaction of' a cyclic a'p-enone enones't o! urp-Dialkylafion rrcns-o,p-disubstituted an akyr rratioe aroros group of I are presenceof HMpT ".J,:#'*t,n trimethvlsilvl ul^o-*" '"';i;;';t';MPi of moderate in enones *u' u'"d for a synthesis iTlaodition' This' '"u"tion initiar the carboxy for a of essential in which 1'"*"' asan equivalent sarkomycin(2) trom cycloii;;;;'

(r

group. 1) Jonesoxid'

O O

(

a A

\--l

)

tt'ocH3 -?8" ,[.atrocH] -so.rnr rr,HMpr.rHF. A \ ( ) ' I z i r c u , o c u ' . 0'L-{-ocH, " 18ea +atoa", 1t4o

cuH,s Si(cH,),

2)cHjL-

Ia.",

ot l

o I ? ..""t I Bcr', ff' ,**cu' .",ocH, A \a+coot"'J \ \\_{ / H.oo.",

( *'ith c-\rc nr.r I

toocH,

L

2

Letters'8'2147(198'l)' rJ. Otera,Y. Niibo' andH' Aikawa'Tetrahedron MAD (1)' 13' 203'

bis(2'6-di'r'butyl'4'methylphenoxide)' Methylaluminum ' --x""'"'.; Ttrr:'-" ti on''i' setectivereduc Kf*fi ::"ffffi*::t'1i::

x :x

,T;1:,Tl"T:il'-:x"::Tl[i:;il""'i';1*'11'lrereren'ia t|1t:* of free ;*,1'""1:lf with 1; reductionof^this more ot tn" r.r, iia"rli-n",on" complexation thefree' originally p'"t"*"tial reductionof x"ton"""""itill complexeA and a phenylgroupcanalso !n""t ot 'uu"itu"n* on "i"tiro"'J o" ketone' hindered,

0i.,"*,.r,r".:l',;Hlt:.i:*l*m;;';"JT,:g-1"

',mln*.:,m:,,lly. :li#*;yt'm;ih:Til,,'.ff

t"t*".n

aldehydesan
20:1)

II I

I

syn4

anti-l (>20:l)

,*,.1l],;?,:€f3i,.'.' cH.

fragme in somc Th€ reaCtio

,o*t"'

C-.Hrri4 reduction(equationI). In contrast,reductionwith zinc borohydrideof the ketone in which the adjacenthydroxylgroup is protectedas the BOM ether is 20:1 antiselective(equationII). The divergentresultis attributedto chelatingability of the of a pentitolgroupcanbe derived BOM group.Thusall four possibleconfigurations from the condensationof 1 and 2.

CH,

(r) cH, cH3o

9u,

QH, (II)

cH, cH3o

.,o-Tc", \

o

.9-1cH, o

IH.J.R

N-Meq The a in CH;C Sclo rapidlyr in the p possible bis(2,6d Exan

cH3co

+ l

+ (CH

OCH2OBzI

OCHTOBzI Jurczak.Am. Soc..ll)!).3981(1987)

I K. Maru

N-Methyl.N-phenyl(dimethylalano)emide

2ll

Methyllithium. (El-Enol silyl ethers.t A new highly stereoselective route to (E)-enol silyl ethersinvolvesadditionof cH.Li to silyl ketonessubstitutedat the a'-positionby a SC.H, group such as 1. The adduct(a) undergoesa Brook rearrangementand

A

cHrli

ll

c.H-asi(cH3)3

I IR

syn-l (>20:1)

i syn4

(cH.).si ot-i -'-

sc6Hs

cH,

\ ..'

-'b", cus}|

I

cH,#

c,H(\y'-'-osi(cH3)l 2 (Erz > 99:r)

ScuH,

1

g

fragmentationto give (E)-2. Use of other alkyl-, alkenyl-,or aryllithiumsresults in somewhatlower stereoselectivities. The (Z)-silyl enol ether (a) of r can be obtainedwith high stereoselectivity by reactionof 3 with C6H,(CH.),SiLi.

o

osi(cH3)rc6H5

tl

c"H^

t

ether, THI

cH," + c^H.(cH.),sili

SCUH,

-t8-r 77%

, C6H5-,4gH, (Z)-4(ZtE> 99:1)

3 rhc ketone s )rt.l antib r l r t ro f t h e l f,c derived

CH.

--t- CH, ,D

QH,

>-fcH,

'H. J. Reich,R. C. Holtan, andS. L. Borkowsky, J. Org.,52,3lZ(lgg7\. N-Methyl-N-phenyl(dimethylalano)amide, (CH.),AIN(CH3)C6H,(l). The aluminumamideis preparedby reactionof N-methyranirine with Ar(cHl). in CH,CI, at 25 ". selectivealkylation of ketones.t This reagentforms a complex so much more rapidly with aldehydesthan with ketonesthat selectivealkylationof a keto group in the presenceof an aldehydegroup with an alkyllithium or Grignard reagentis possible.The oppositechemoselectivity is achievedwith the bulky methylaluminum bis(2,6-di-r-butyl-4-phenoxide) (MAD, 13, 203; this volume). Example:

cH3co(cHr)rocHo + MAD

\--O 'OBzl

OH

cHl|-i

-.CHt + (CHr)rAlN-CuH,

cH'cl" -78'

cHjco(cHt

I

+ (cHr)2c(cH2)rocHo

72Vo

l:0

44Vo

l:62

'K. Maruoka, Y. Araki, and H. yamamoto,TetrahedronLetters,29,3l01 (l9gg)

2t2

Methylthiomethyl lolyl sulone

Methylthiomethyl tolyl sulfone (13, 192-193)' can be converted to syn'F Hydroxy-o''a,nino acids't ct-Hydroxy aldehydes by reaction with the anion (1) one-carbonhomologatedp-hydroxy-c-amino acids ofmethylthiomethyltolylsulfonetottowedbytrichloroacetylisocyanatetoprovide in CH'OH' 2 cyclizesto the trichloroacetylcarbamate2' When treated with K'CO' by Pummererrearrangement the oxazolidinone3. Oxidation to a sulfoxidefollowed the p-hydroxy-a-aminoacid to hydrolyzed is providesa methyl thioester (4), which i in qSEooverall yield from the aldehyde'

I al

' l

r) r, -l!'^.

:iri'it!itqcH,:-.A--zso2Tcr " cti'ofr' cH3qHcHo 6% " -,utu -l 2) CH3SO2CI

I orBS

irr'

K,co. CH3\

I

,CHSOzTol

/1

OVNH

I

l.o*i?ttt',

3 1mz,y I r; ctqx.co,u (cFco),o(877,) l2)

2

.",-TA.ooH OH

.coscH3

CH,

NH,

# \*'

o

rM.Hirama,H.Hioki,andS.It6,TerrahedronLetters't)'3125(1988)'

ll n !j

p u q a

rrredto non (1) provide rllzesto rgement ino acid

Nafion-H. Review. Olah er a/.rhave revieweduse of this resin sulfonicacid as a solid catalystin organicsynthesis(181references). 1G. A. Olah,P.S. Iyer,andG. K. S. Prakash, (1986)' Synthesis.5l3

lTol

Nickel, activated(12, 335). o-Xylylene. This compound,or a relatedspecies,can be generatedwith acalkenes'' tivatedNi from an o,ct'-dihaloo-xyleneand trappedby electron-deficient Example: LCO'H (9O7o) Dr.O (8?7o)

cH,

y'-1.ctt"' I ll

\A.r,u,

",.o"r.r0"l ? *-,';;xr*'

R ' l

OH

I - 2 OsOr +

and in tri lower as substratc catalyzd 88Voe. The o pared an to the ql quinolinc prevail in

ee 20-88Vo

and turnover numbers This new processhas one unexpectedbenefit:the rates with the;esultthat the amountof the toxicandexpensive areincreasedsubstantially The rate accelerationis OsOois considerably,educ"d (usually0'002 mole 7o)' attributedtoformationofanOsOa-alkaloidcomplex,whichismorereactivethan freeosmiumtetroxide.Increasingtheconcentrationoflor2beyondthatofOsO. ofthe diol' In contrast producesonly negligibleincreasein the enantiomericexcess quinuclidineitselfsubstantiallyretardsthecatalyticreaction,probablybecauseit initial osmylation'other binds too stronglyto osmiumtetroxide and inhibits the the catalyticprocess' chelatingtertiary aminesas well as pyridine also inhibit Afurtheradvantageofthisligand-acceleratedreactionisthatadirectingfunctionalgroupisnotessentialforenantioselectivity'asinasymmetricePoxidation ee Even simple alkenesare convertedinto diols in 20-88Vo and hy-drogenation.

Ph\"co'Et 95Va(85Voee)

Me\'zcotet 17Vo(53Voee)

en"co2Et 9l7o (74Vo ee\

OMe I

vbz P6\"Ao't"

90% (70Voee)

Z;'-'r''oEt I OEt

'K. Tomio 2 ldem. Ta r B. M. Trt 'G. Soll.d 5E.N.Jr

ll0. l%t nE.N.Ja

Am. Sx..

95VoQSVoee) Oxezrbct

Enlna with the v to efiect cr intermedu 89Vo(50Voee)

90Va (67% ee)

90Vo(63Voee)

for enantk

Oxazeborolidines

n9

and in high chemicalyields.In general,(Z)-disubstitutedalkenesare oxidizedwith lower asymmetricinductionthan the (E)-isomers,and aromaticalkenesare better substratesthan aliphatic alkenes.Thus trazs-stilbeneis converted by the reaction catalyzedby I at 0-4" for 7 hours into (+)+hreo-hydrobenzoinin 89voyield and 88Vaee. The orange-red1:1 complexof the dihydroquinidineand OsOohas been prepared and shown to have the structureshownin Figure L The osoo is coordinated to the quinuclidinenitrogen by an unusuallylong bond, and is remote from the quinolinering. 'H-NMR studiessuggestthat a slightlydifierentconformationmay prevailin solution.6

rethc lc.j

h.'r. Fl\ c tn

l\

th.r:l

).(). Itr.t.l l{

ll

)ihcr

o

oAlt"' CH,

f u n cbll,)n (' ce

' K. Tomioka,M. Nakajima, andK. Koga,Am. Soc.,l09,6213 (198't). 2ldem, Tetrahedron Leuers,2E,l2gl (1987'). r B. M. Trost,G.-H. Kuo,andT. Benneche, Am. Soc.,110,621(1988). nG. Solladi6, J. Hutt, andC. Frdchou,Tetrahedron Letters,8,6l (1987). 5E. N. Jacobsen, I. Mark6,W. S. Mungall,G. Schrdder, andK. B. Sharpless, Am. Soc., 110,1968(1988). 6E. N. Jacobsen, S. J. Lippard,I. Marko,C. P. Rao,K. B. Sharpless, andJ. S. Svendsen, Am. Soc.,in press. Oxazaborolidines,chiral. Enantioselectivereductionof ketones.t rhe ability of diboranein combination with the yic-aminoalcohol (S)-2-amino-3-methyl-1,1-diphenyl-1-butanol (fi|, 31) to effectenantioselective reductionof alkyl aryl ketonesinvolvesformation of an intermediatechiral oxazaborolidine,which can be isolatedand usedas a catalvst for enantioselective boranereductions(equationI).

Oxazaborolidines

(r)

/9H,\ /C^H. " H"'.KCuHs bn HrNt

CH.-{

CH, BH,

fH'

++tir,*H, Hry\B.o H

Thisobservationhasledtothepreparationofmoreeffectivebicyclicoxazaborolidinessuchas l, preparedfrom (S)-O-2-(diphenylhydroxymethyl)pyrrolidine catalyzeborane reduction and BH3 (1a) or methylboronicacid (1b)' Both reagents g5vo ee, by face-selectivehydride of alkyl aiyl ketonesto furnish (R)-alcoholsin >

the con tion (D the con bromidt Ths oxiranq mole % of base

transferwithinacomplexsuchasB.Catalystlbissomewhatmoreefiectivethan

H f.H'

a-l--\toH' -N=B-_n

u"',

-

frsl

HsOH Ri""R,

Eu

enantio!

2

1r,R=H 1b, R = CHr

corresponding(R)-alcohol in la, and also reducest-butyl methyl ketone to the 97Voee. route to trans-2,5'diaryl' oxazaborolidinelb was used in an enantioselective by lb furnishes Reductionof the keto ester3 with BH. catalyzed tetrahydrofurans.2

with the beenusc platelerI golideA

(cH2)2coocH3 cH30

cH3o

cH3o

'E.J.C 'E.J.Cq \ Idem. l.

Oxezrborolidines

LlXaza-

rohdine duction hr dride i\ e than

Al

the corresponding(R)-alcohol,which cyclizes(NaH) to the (R)-lactone4. Reduction (DIBAH) of 4 resultsin a 1-lactol (1:1 isomers),which after conversionto the correspondingc-bromo ether coupleswith 3,4-dimethoxyphenylmagnesium bromide to afiord rrcns-(2R,5R)-S in 70Voyield (translcr.s selectivity: 10:1). This enantioselective reductioncan be usedfor synthesisof chiral l-substituted oxiranes.3Thus reduction of 2-chloroacetophenone with BrHu catalyzedby I (1 mole vo) resultsin (s)-( + )-(chloromethyl)benzenemethanol, whichin the presence of baseconvertsto (S)-(- )-phenyloxirane(styreneoxide). Brllo, I

NaOH, HlO

t.t,--la. | -G;- *[',X6., THn 25.

-d

22

coHs-.-z H."'\O

o (96.5voee)

r.g,oH .RL

(

Enantioselectivereduction of enones.a rhis methodologycan be usedto efiect enantioselective reductionof enones.Thusthe enone2 is reducedby BH, catalvzed

!

o

OH

#.",cH(ocH3),# 2 rlcoholtn i.: -'liarYlfurnishes

6rcH,cH(ocH.), t(93Voee\

with the (S)-oxazaborolidine (1b) to the (R)-alcohol3 in 93vo ee.This alcoholhas beenusedfor a total synthesisof naturalginkgolideB (4)5,a potent antagonistof plateletactivatingfactor. This ginkgolidecan be convertedby reductioninto ginkgolide A (5)5,an insectantifeedant.

f,o '..c(cH3)3

4,R = OH 5,R = H 'E. J. Corey,R. K. Bakshi,and S. Shibata,Am.Soc.,f09,5551(1987). 2 E. J. Corey,R. K. Bakshi, jg25 (1987). S. Shibata,C.-P.Chen,and V. K. Singh,rbld., 1Lg9, 3 ldem,J. Org.,53,2861(1988).

U0

Oxrzolidinones

T

(1988)' aE. J. corey andA. v. Gavai,Tetrahed*i ,:":':::?' 3201 (1e88)' ' ;. ;. ;;i, .ia n. r. Ghosh,ibid" 2e' 320s

ddo

Fhr 7.O

Oxazolidinones,chiral' (5) can be pure a-azido carboxylic acids a-Azido acids't Enantiomerically N-acyloxazolichiral of of dibuiylboron enolates obtained by brominati""lNnsl azide' The dinones (2) followed uf Ai'pr"t"t:tt.Yitl.:tltamethylguanidinium racewithout yield 5 with LioH in excellent products (4) can u" rtyi'JyJ"J to

9

q

o

"A"A-,* \ /

o

lli;to'''**', o\4.* \

4,,

/

4",

, Br

!hv routl

c

JL

N,.' ":\.j\o&-86qa q",

ft'

4

3 (95:5)

t

atiq

rnr-r**lft,o"

o

-^At* rrv I N3 5 (> 99:1)

i

mization.Transesterificationtobenzylestersof5canbeefiectedwithbenzylalcohol only slight racemization' ""0 iitOeal a in 80-947oyield with of the 3-chloroacetyl-2-oxazolidinp'Hydroxy'a-amino acids'' The enolate These high diastereoselectivity. 2.with aldols one 1 reacts*ittr atoetridl-si"'gi"" (4)' acids'suchast-'cllo-threonine areusefulprecursorsto anri-p-hydroxy-a-amino

O "'\''\

O

imid wilh for r efier

l) NaN'. DMF (707o) 2) LioH )

l) Bu:BOTf'N(C:H')' 2) CH,CHO )

V. "cHr C'

cuHi'

2 (95:5)

o

o

H:.Pd,c, "o\.Aa",:

"oi-X.n, : N, 3

NH,

H

CrH,

0xazolidinones

can be lrazolile The It race-

The synthesisof the rare amino acid 3-hydroxy-4-methyrprorine (E)3involves an aldol reactionof the oxazolidinone5 with methacroleinto provide the ct-bromoB-hydroxy adduct 6. Azide displacementand removal of the chiral auxiliary gives 7. on treatmentwith dicyclohexylborane, 7 undergoeshydroboration--cycloalkylation to provide,after hydrolysis,the methylesterhydrochloride(E) of (2S,3S,4S)3-hydroxy-4-methylproline in >97vo de. This cycloalkytationshould be a useful route to cyclicamino acidsas well as pyrrolidines.

?

Y* \.

p

.3^.,,,,

g

dff*

o

o

lliii.$',I 1",,

"}\\:H, .

"Bzl

H

"Bzl Br

CH,

6 (97Vode)

cH3o

cH, jlltll",o

CH:

,*1'CH$

,,/.R 2S,3S,4S)-E (>97Vode)

I

a. lt

plalcohol razolidintr These r n r n e( 4 ) .

Diastereoselectivealdol rcactions.4 The boryl enolates of chiral crotonate imides(1) and (2) reactwith aldehydesto form adducts(3) and (4), respectively, with highdiastereoselectivity andcompletec-regioselectivity. The methodof choice for reductivecleavageof the adductsis formulatedfor 3; hydrolysiscan also be effectedwith LiOH and H,O,.

cH(cH3)'

: ()\11 t 709r)

9

flVcH,-,j[# b-( o

I (X"-COCH:CHCH3)

OH

A.t,

9H,?

C.H'\^N )-.,,4-cnt \ i '

o{o

IH 2 (X--cocH:CHCH:)

o o H l l '

l) BulB 2) LiBH. 3) HrO!

xAln:

CH:CHz

OH

OH t

:

\z^n : CH:CHz

3 (>98Vo de)

o o H i l t 8s-,3ilx-aR CH:CHz 4 (>98Vode)

HrOr, OH

€

8%

o o H i l t nolln

I CH:CHz

ZU

Oxazolidinones

Thisaldolreactionwasemployedforanasymmetricsynthesisoftheazetidinone gfromtheadduct(5)ofacetaldehydeandl.5Azetidinonegisaversatileprecursor stablealdehyde6, obtained to the antibioticthienamycinro. it " configurationally with allylzincchlorideto addition by ozonolysisof the silyiether of 5, undergoes amide E' This N-methoxy the to afiord 7, which on transaminationis converted productisconvertedinseveralstepstothedesiredgin34vooverallyield.An interestingfeatureofthissynthesisistheearlyincorporationofthehydroxyethyl sidechainatCu,astepthatisdifficulttoeffectafterformationofthep-lactam ring.

(r) cHi

r ()r OSiRI OH CH: I IJr)BurBorr I H Jl 6:"-^'. ii zici,cHo, - L.*_, r r rAi)clIQ ,E 2 CHa^\k % l I

cH,:cncu'znct, *n

I

I

€'x'

oA*'

I t

6

S

R3Si \-CHz

CHi

cHloNH,Cl. A(cH,). 79Va

ipH,co,ctl,

)

CHJ

CH;

\-cH,

SCH2CH2NH.-

10

AsymmetricDielyAlderreactions,6Unlikemethylcrotonate,whichisaweak whenactivatedby a dialkylaluminum dienopiite,chiral(E)_crotonyloxazolidinones chloride(1equiv.)arehighlyreactiveanddiastereoselectivedienophiles.Forthis (Xn) derived from purpose,the unsaturat"Ji.id"' formed from oxazolidinones those derived than (S)-phenylalanolshow consistentlyhigher diastereoselectivity effectoJ:n" On"lll,gtoup is atfrom (S)-valinolor (15, 2R)-norephedrine'The of the aromatic ring' The tributed in part at least to an electronicinteraction reactionsoftheunsaturatedimidelshowninequation(I)aretypical.of,reactions ofunsaturatedN-acyloxazolidinoneswithcyclicandacyclicdienes.AlltheDiels_ and high diastereoselectivAlder reactionsshow almostcomplete endo-selectivity ity.oxazolidinonesareusefulchiralauxiliariesforintramolecularDiels_Alder

reaction c hancethc Hydrd imides. is THF at n

,D. A. EV ,D.A.E 3D.A.E {D. A, E (1986). 5D.A.E uD.A.E

p-Oxo{ agent,a I of Q,H.I= vic-D, crs,vrc-di with buta

R. T. Hen

Oxodipcn

9tia,

sulfone w

Oxodiperoxymolybdenum(pyridine) (hexemethylphosphoric rriamide)

o tl

drn,tne 3;gJsOI btrrned

This :lJ .{n x r e t h rI -lrclam

fi....,\os,r

LiOBzl

-

lrrdc to

54%

cH

t

cH.

(D I (Xe-COCH:CHCH3)

o l

9H, '

l

"-"0 "''t"0,,oon r/'\""cooH -,-,oon ^ * - f,-

ll

cH.,

I

*H,

(95:1)

AcH, -rt

reaction of trienes; they not only improve endo-diastereoselectivity, but they enhancethe reactivity. Hydrolysisof the Diels-Alder products,particularlythoseformed from hindered imides' is best effectedwith lithium hydroxideand excess30vo Hro2 in aqueous THF at room temperature. 'D. A. Evans,J. A. Ellman, andR. L. Dorow,Tetrahedron Leuers,?i,ll23 (lgg7). ' D. A. Evans,E. B. Sjogren, A. E. Weber, andR. E. Conn,ibid.,2S,39(19g7). 3D. A. EvansandA. E. Weber, Az. Soc.,l0).2151(1987). o D. A. Evans'E. B. sjogren, J. Bartrori,andR. L. Dovr,Tetahedron Letters.n.4g5i 0986). 5D. A. EvansandE. B. Sjogren, ibid.,27,4%l(1986). 6 D. A. Evans,K. T. Chapman, andJ. Bisaha, Am. Soc.,U0, l23g(l9gg).

tr .r \\ eak lumrnum . Lrrrthis rcJ from l Jcrived rup is atnng. The

p-Oxobis[phenyl(trifluoromethanesulfoneto)iodinel,OU(OTf)C6H.], (1). The re_ agent, a mildly air-sensitive,yellow powder, precipitateson reactionof 2 equiv. of CuHrI:g with triflic anhydride in CHrClr. vic'Ditriflates.r The reagent reacts with alkenes in cHrcL at 25o to form cis,vic-ditriflates(50-70voyield) and the co-productsC.H5I and cuH,I:g. It reacts with butadieneto give an 89:11mixture of 1,4- and 1,2_adducts. R. T. Hembre,C. P. Scott,andJ. R. Norton,J. Org.,52,3650 (l9g7).

rc actions hc Dielso.ciecttvel.-Alder

oxodiperoxyrnolybdenum(pyridine)(hexamethyrphosphoric rriamide) (MoopH). oxidative desulfonylation; polyenes. oxidation of the anion of a primary sulfonewith MooPH resultsin a p-hydroxysulfoneformed by condensationof

2fi

Oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triemide)

so2c6H5

c'H'

5'iS"*= c,HAf 5cH2so2c6H

'M.c4 4,627 , F . P .B (1e86

OH (synlanti = l:l)

theanionwiththealdehydeasformedonoxidation(equationl).Thisreaction system' canbe usedto prepareterpenepolyenescontainingan (E,Z,Z)-l'3'5-triene Example:

9H,

9t,

OrtrSGt YA and is b vitro by diisoprc

so2coH5I ) L D A 2) MoOPH '76Vo

csA/W

QH,

CH,

I l ) A c : o ,D M A P rHF J2) NaH,

IIv catalyr oxygen Exa

CHi

'M.R. ,w. Ad andE.

(E,Z,Z'82Vo) alkynesare a-Diketones.2 In the presenceof Hg(OAc)r, a variety of internal alkynes terminal oxidizes oxidizedto o-diketonesin 55-90voyield. This systemalso to a-keto aldehYdes. Example: MoOTHMPT,

cH3(cH')'c-at -#-

?

cH3(cH')3d-cHo

Oxygen'singlet

A7

' M. Capet,T. Cuvigny,C. H. du Penhoat,M. Julia, and G Loomis, TetrahedronLetters, 2t,6273 (1987). ' F. P. Ballistreri,S. Failla, G. A. Tomaselli,and R. Curci, TetrahedronLetters, 27 5139 , (1e86).

hrs reaction ienesvstem.

Oxygen, singlet 3-Alkyl-4-hydrorybutenolides.t This group is presentin somemarine sponges and is believed to arise from 3-alkylfurans.This transformationcan be realizedin vitro by singlet oxygenoxidation in the presenceof a hindered basesuch as ethyldiisopropylamine.

*r-

'o,.

(.)*

,oa.r, CH,

| *>- I

\-

*"o+o L"f"f"]

Hydroxy epoxidation of dienes.z Photosensitizedoxygenationof dieneswhen catalyzedby titanium(IV) isopropoxideresultsin an epoxy alcohol,formed by an oxygentransferfrom an allylic hydroperoxide. Example:

-5H3

'"'qo,

*=5:,

\7cH' CH' H,C

CH'

'M. R. Kernanand D. J. Faulkner,t. Org.,53,2773(1988). 2W. Adam, A. Griesbeck,and E. Staab,TetrahedronLeners,TI,2839 (1986);W. and E. Staab,ibid.,29,531(1988).

r\.,CH: I CHr

nl alkynesare rmrnalalkYnes

Palladium(Il) acetnle. Heck coupling with cyArylation of cycloalkenes't Aryl halides undergo The reaction involves addition cloalkenesin the presenceof a pallaiium catalyst' bond followed by elimination of a of an arylpalladium intermediate to the double palladiumhYdride. Example:

' R .( :A.I ]S.K

(ls

P&

, ylidc with €tat E

KOAc Pd(OAc)r, Bu.NCl,DMF 2ff, CH"CO, u%

p-CHrCOrCuHnI+

Allyticacetoxylation'Pd(OAc),inHOAccaneffectallylicacetoxylationof and only a catalyticamount is alkenes,probablyvia a n-allylpalladiumcomplex' requiredinthepresenceofacooxidantSuchasbenzoquinone-Mnoz.Thereaction isnotusefulinthecaseofsimplealkenesbecauseoflackofdiscriminationbetween can be regioselectivein the caseof the two allylic positions, but ihis acetoxylation alicyclicalkenes. ExamPles:

QAc

oAc cH3\,,/'\^c

H,

-so;

cH"')\/-cn"

* cH'-A/cH, l:1

l-AlkenylstannanesundergohomoOxidativ e couptingof alkenylstannanes't hydroperoxidein the presenceof coupling to 1,3-dieneswien treated with t-butyl conditions l-alkenylstannanescouple catalytic amountsof Pd(OAc)r' Under these to give 1,4-dienes' with 2-alkenylstannanes ExamPles: 28

r B .I

Prt I

Palladium(II) rcet&tFHydroquinone-(Tetrrphenylporphyrin)cobell r_BuOOH,

cuH'.-.2-sn(crH5)33#r..CuHt.r/',.,/)r--cuH, 687, cH,:CHCH,Sn(C,H5)3 J

CuH\,A4H, ith cyldition )nofa

)I )

Itlon of Klunt is tactlon )el\ een caseof

(1N% E) 'R. C. LarockandB. E. Baker,Tetrahedron (1988). Letters,29,905 2A. Heumann, B. Akermark,S. Hanson,andT. Rein,Org. Syn.,submitted (l9gg). 3S. Kanemoto, S. Matsubara, K. Oshima,K. Utimoto,andH. Nozaki,Chem.Letters,5 ( 1e87). Palladium(Il) acetate-Bis(1,4-diphenytphosphine)butane (dppb). Dienones. Alkynones,which are readilyavailableby additionof lithium acetylidesto N-methyl-N-methoxyamides (ll,20z), isomerizeto dienoneswhentreated with Pd(oAc), in combinationwith a phosphine,particularlydppb. The actual catalystis probablya hydridopalladiumacetate.' Examples:

o

o

^.AN-ott' l l ' r ' \-,

C",

1L\

c'H'

| "** [ --

,ro, o*o J.o{oo"1,, ..{.H,

o

c.H/\-i OAc

7ctt,

3ohomocscnceof es couPle

N

/.ocH3

I cH3

"'c'H*(cH2)3cHl

"*l

.,'&,",

lB. M. TrostandT. Schmidt, Am. Soc.,1l0,2301(19gg).

Palladium(II) acetate-Hydroquinone-(Tetraphenylporphyrin)cobalt. lr4-Oxygenation of lr3-dienes.t Conjugated dienescan undergo an efficient

Psurdium(It) acetate--Triphenylphosphine

this triple catalyst. The reactton biomimetic aerobic oxidation in the presenceof complex' and.the cobalt is believedto involve a r-allylpalladium-benzoquinone to benzoquinoneby O'' Salcatalystis required tor reoxidaiion of hydroquinone lessefrcient for this purposethan comine (2,360)or cobaloxime(11,135-i36)is of 5 mole Vo eachof Pd(OAc)" cobalt(TPP)(12,138-139).Thus in the presence (1) is oxidized in HOAc coniyO.oiuinon", and Co(flf), 1,3-cyclohexadiene taining LiOAc to 2 in 89VoYield' Or. HOAc' LrOAc

--#U(j

Aco...'UtsoAc + H2o 2 \ranslcis = 90:10)

I

Am' Soc''109' 4750(1987)' Biickvall,A. K. Awasthi, andZ' D' Renko'

Palladium(Il) acetateTriphenylphosphine' pOiOe")" particularly when complexed with Cyclization of 1,6-e)yne''' to a five-memberedring phosphine ligands, .un "'t'"tt cyclizaiion of 1'6-enynes of the sesquiterpene stepin a synthesis system.This cyclization,l"+2,piovides a key sterepolide(3).' atrft CH;

>_\.CH2OR2

pd(oAchlp(c6H,),r, - r^r.-/-(t^' 75q? CHi _$ AcO'

|H.OR'

Pd sib bc

cq prl c}l cal pfl

tet

3 formed; a. quaternary T:!t-t-lt This cyclization is possible even whenCoH'HC:N(CHz)z in such reactions, N,ftl-Ui'(U"nzylidene)ethylenLdiamine' ligand'' the as P(CtH')' than N:CHC.Hs (6), can be more effective

CH, R3SiO

Prlledium(Il) ocetrte-Ttiphenylphosphlne

E reactlon the cobalt rr O,. Salrposethan PdtOAc)r, lO.{c con-

crnrHc:f,N:cHC6H5 6 This cyclizationcan arsobe used to obtain substitutedpyrroridines, as in the conversionof 7 to 8.3

sdN14cHroR

9H'oR

(Rf)Pd(oAch

| _a_

"\n

BzlN

fi%

\

I

l ',,AcH,

t

lered with bcred ring quiterpene

cyclization of a 1,6-enyneto a methyrenecyclopentane can be effectedwith a Pd(0) catalystcomplexedwith a phosphinerigandin combination with a trialkyrsilaneas a hydride donor (equationI).a Under theseconditions a 1,7-enynecan be cyclizedto a methylenecyclohexane.

(r) E E

cH2oR

s_88% p- LA1cH2)2OR

E = COOCHT

OR

Intramoleculararylation of arkenes. The intramolecutarpalladium-cataryzed condensationof aryl halideswith an alkenegroup (Heck aryiations) can actuaily proceedmore readily than the original bimolecular version. These intramolecular cyclizations typicallyproceedin acetonitrileat room temperature,particularlywhen catalyzedby Agrco3, which also inhibits isomerizationof the double bond of the product. They can be used to obtain spiro, bridged, and fused systems.Even tetrasubstituted alkenescan participate,with formation of quaternaiycenters.6 Examples:

coocH"

coocH" ir tttrmed;

r:N(CH:):

CH. ( lH, I

al^Y,\ l l l l

\/

l

'*o1?i31*'', E

6

v

o

(30:1)

t/V

::b ._

69%

+ 3.4:l

endo-isomer

252

Palladium(Il)rcetrtF'Tiis(2,Gdimethoxyphenyl)phosphine

This intramolecular Heck cyclization can be extended to diunsaturated aryl iodides,which can undergotwo consecutivecyclizationsto form polycyclicsystems'i Examples:

CH,

P&a A

as r@ memb Err

(CHr)rCH:CH, -G

cH3' 0' resultsin the bicyclicenone3 in livo yieto.rtre reactionmay invorve conjugate additionof 2 to I to give a ketene(a) with lo* oi titr,iun,,phenoxide.Several other

*t - l

I L'3oo

C (CHr),

phenyl estersof propioricacids undergothis reaction,which may be generarfor vicinal diesterdianions. This bicyclicketo ester(3) wasused for synthesisof the ginkolidebilobalide 4.

5-PhenyldibenzoPhosPhole

1-Phcrtf Asyt with (Rl goup to

o

Y o

(

4 r E . J . C o r e y a n d W . S u , T e t r a h e d r o n L e t t e r s , S , 5 20a9l 8 7 ) ; i d e m ' A m 'S o c " 1 0 ! l ' 7 5 3 4 (1987).

I

(c6HfDBP' 1).

S-Phenyldibenzophosphole'CuHr-d

Thephosphole,m.p.g5-gT",isobtainedinT4Voyieldbyreactionoftetraphenylphosphoniumbromide with lithium diethylamide' (E|.SelectiveWittigreagents.|ThereactionoflwithlithiuminTHFprovides NaNHzin THF gives LiDBP, which on reaction*ittt un alkyl halide(2 equiv') and iodideor butyl iodide' a salt-freeylide suchas2 or 3, formed by reactionwith ethyl at 78" but the-intermediate Theseylidesreactreadilywith aldehydes respectively. for are unusuallystable and require temperaturesof 70-110" oxaphosphetanes ratios E/Z in obtained conversionto the phosphineoxide and the alkene,which is aldehydes' c-branched with observed is (E)-selectivity of 6-124:1.Highest Examples: .Bzl

ttt----" -c,H.

DBPa"" ---\CHCtt3

+BzlcHO-

2

-CoH, +BzICHO._ ---\cHp, D BP: 3

A

i

L

DBP-O

rr tt-a:"/ -\H

,

664o

C.rH,

T

DBPq H5

Bzl/ EIZ -- 23:l

CzHs

Pr...Bzl ^, o T--l I L (Ava DBP-O

o ll

CHr

HBzl-

o ./Pr+ D-^lt^ BPBu

) C : C _ -H

EIZ = lO:.1

I E. Vedeisand C. Marth' TetahedronLetters'8' 3445(1987)'

t !

molecula lactone f, providcs ! rY. Hirar

Pherybl yBa dation of ; suspende Examp

Phenyliodine(lll)bis(triffuoroecetrte)

El

l-Phenylethylamine, C6H'CH(CH3)NH, (1). Asymmetric intramolecular Michael cyclization.r Reaction of the ketone 2 with (R)-( + )-1 (1 equiv.) generatesan enaminethat addsto the unsaturatedester group to give 3a. The yield and the ee of 3 are markedly improved when 5 A

?, . \ , \ (8.", +

r09.7534

\.oo.,r,

(R)-r,s', 5A

?, a*\

18%

\./..:

{'Cu,co
90vo yield.Monohydricphenolscanbeoxidizedtop-quinonediketalsonoxidationwith 2 equiv. of the reagentin CH.OH at 25'' Bzl

( \:/

Vot

-J

Bzl

t:13"', cu,{-!o

+ 2cuH,I(oAc)2$qa

cH,d

E/

from hydrazine Diimidefrom hydrazine hydrate'2 Diimide can be generated CH'CI' in compound iodine hydrateby oiidation with this hypervalent NH2NH2

c6H5I(oAc)') [HN:NH]

+ c6H5I

rA. Pc zR.M rP.J.S { K. Fun

&Pbcq t-A (-)-l ( agentsi reaSen auxilia yield u-

&

aoc,lc"H.c-cc"H, cis-CeHsCH:CHC6Hs RC-COzCR'' A wide varietyof thesepreviouslyunAlkynyl carborylates, 1' as formulated for known esterscan be prepared in a two-step procedure from the alkynyl benzoates(2).3 C6H5I(OCOCH,)z* 2C6H5COOH*H'

jEq C6H5I(OCOC6H')' RC-CO,CC6H5 + C6H5CO2Li+ C6H5I 2 (2'1-s7%)

l",o'

J

RCHTCOOH + C6H5COOH

Hl

L.

CL 8-phen glycolk ratio ar procecr

E-Phenylmentholand -menthone

E9

Cyclic acetals. In combinationwith iodine, this reagentresembleslead tetraacetatein the ability to generatealkoxy or aminyl radicals(12,243)under thermal or light activation.This radicaloxidationcan be usedto convertB- or 1-hydroxy ethersinto dioxolanesor dioxanes.4

9H'

I, I,, qll hv 92Vo

o(cHr),oH

cH(cHr),

cH(cH3)' rr phenols henolsare I n >90Vo h t r o nw i t h

)

Lhr drazine

q)

I A. PelterandS. Elgendy Letters.T), 677( 1988). , Tetrahedron 2R. M. Moriarty, R. K. Vaid,andM. P.Duncan.Syn.Comm.,U,703 (1987). I P.J. Stang,M. Boehshar, H. Wingert,andT. Kitamura, Am. Soc.,110,3212(1988). I K. Furuta,T. Nagata,andH. Yamamoto, (1988). Tetrahedron Letters,29,2215 E-Phenylmenthol(1) and -menthone. t-Amino acids.r Brominationof the ester(2) formedfrom N-Boc-glycineand (-)-1 (R*OH) providestwo bromides(3), which on reactionwith Grignard reagentsare convertedinto a highly reactiveiminoacetate(a), to which Grignard reagentsadd with (S)-stereoselectivity to provide4. Reductiveremovalof the chiral auxiliarygivesprotectedl-amino alcohols(5), whichon oxidationand deprotection yiefd r-amino acids(6) in 82-95Voee. Highestopticalyieldsobtainwith i-BuMgBr.

s ,*fr--J-o*# r""Fy,fl-oR. ["'"*o,-i-o*.] Br 3 ( 1 :l )

r r o u s l yu n nulatedfor

a Lr - C6H5l

zrvolcH,ugnr J

cooH I

H2N-C-H I CH, t-6 (92Voee)

l) RuCl3,NaIO.

2I+-

18%

H

H

tot*-.g^ot | CH, 5

"^-

+

t

o

l

Bo"N.-{Ao*, I CH, 4

Chiral glycolates. The chiral dioxolanes1 and 2 are prepared by reaction of 8-phenylmenthone with a protectedderivative, (CH3)3SiOCH,COOSi(CH,)r, of glycolicacid catalyzedby trimethylsilyltriflate. They are obtainedin about a 1:1 ratio and are separableby chromatography.Alkylation of the enolatesof 1 and 2 proceedswith marked diastereofacialselectivity.After separationof the major

8-Phenylmenthol rnd -menthone

260

isomers, ethanolysisprovides (R)- and (S)-c-hydroxy esterswith recovery of the chiral auxiliarv.2

t',

IP.E ,w.H

\.t")

cHiEF,H,

2

I I) LDA

I l) LDA

fzi nx

t ldct^. . J. d'A

*ffi-"

I

when t tially c crotoo group.

Pbcrti

u

to l.}' 2-phe Exr

Irl **

t",

crHroH

RfHcooc'Hs UkYR''fi49'' o+.^ -l oH .tGg", (,, (R)

RQHCOOqH, & I OH

(s) (14-58:l)

(24-123:l)

Aldol reactionsof 1 and 2 can be used to obtain any one of the four possible stereoisomersof a,p-dihydroxy esters.rThus I reacts with aldehydesto provide (2S)-aldols,and 2 reacts to provide (2R)-aldols. The synlanti ratio of the aldols can be controlled by the choice of the enolate counterion. Thus lithium or magnesium enolatesprovide mainly anti-aldols,whereassyn-aldolspredominate with zirconium enolates. Ethanolysis of the purified adductsyields the optically pure c,p-dihydroxy esterswithout epimerizationwith recovery of S-phenylmenthol. Chtral p-amino esterc.' The conjugate addition of primary amines to alkyl crotonates proceedsin satisfactoryyield when carried out under high pressure. Frenchchemistshaverecentlyexaminedthis reactionusingcrotonatesderivedfrom chiral alcohols.Thus addition of diphenylmethylamineto 8-phenylmenthylcrotonate proceedsin85-90Vo chemicalyield and in 60Vode. Optical yields are increased

"'0"', + (C^H.),CHNH" ' so%

Hr&

^ ylenic elimin

RCH/

' J.-8. :T.G rT.G

R-ooC)

:

(cuH5)rcHN#cH3

Utt3 | Utt3 9-C,oll,

R >- 99o/ode

Ptcrt A cesiun methi

Phenylsilane-Cesium ftuoride

the

251

when the phenylgroup is substitutedin the para-positionby bulky groups.Essentially completediastereofacial control is obtainedby useof 8-(B-naphthyl)menthyl crotonatebecauseone face of the double bond is well shieldedby the naphthyl group. IP. Ermert,J. Meyer,andC. Stucki,Tetrahedron (1988). Letters,29,1265 ' W. H. Pearson andM.-C.Cheng,"/. Org.,51,3746(1986). 3ldem,ibid.,52,3176(1987). aJ. d'AngeloandJ. Maddaluno, Am. Soc.,10E,8112(1986). (l),10,315;11,407-408;12,394. Phenylselenenyl benzenesulfonate, C.II5SO2SeC6H5 2-Phenylsulfonyl-lr3-dienes.r This reagent undergoesselective 1,2-addition to 1,3-dienes,particularlyat low temperatures.Oxidationof the adductsprovides 2-phenylsulfonyl1.,3-dienes. Example:

:H.

ible rrde dol: nagr ltn Pure 1. ilkr I ure.

r,*r,cr, l-

s,c?vvcH, 4

so,c^H.

I

l..r,t.--A_,1.",1

"ffi*

?o'cuHt

cuy''v/\gH,

Addition tol-alkynes (10,408). Terminalalkynescanbe convertedinto acetylenic sulfones:or into allenicsulfonesrby reactionwith I followed by selenoxide elimination. RCH' RCH'C-CH

+ + ArSO2SeCoHs r

)< C6H5Sd

SO,Ar 'H

"*/

RCH2C:CSO2Ar

-;s_esq, - ^-- | t) loe | !1 tol

TOm lonase d

'J.-E. Bdckvall, (1988). C. N6jera,andM. Jus,Tetahedron Letters,29,1445 'T. G. Back,S. Collins, U. Gokhale, andK.-W.Law,l. Org.,8,4776(1983). I T. G. Back,M. V. Krishna,andK. R. Muralidharan, (1987). Letters,E,1737 Tetrahedron Phenylsilane{esium fluoride. Azomethineylides. Reductionof oxazoliumsalts(1) with phenylsilaneand cesiumfluoride providesan unstable4-oxazoline(2), which can react as an azomethineylide with a dipolarophilesuchas DMAD to give a dihydropyrrole(3).'

26i2

N-(Phenylthio)morpholine

Example:

.r,y\

H

ft'*-

c;H5siH,,

a;.,r5;',.r, RCOOCHyI Aliphatic aldehydescan be converteddirectly to methyl estersby PDC (6 equiv.) and methanolin DMF in yieldsof 60-857o.The methodis not usefulin the caseof aromaticaldehydesor of higher esters.

)rln

u\ t

[('

lB. O'ConnorandG. Just,Tetrahedron (1987)' Leuers,28,3235

Rt

R2

Rffi

F.s

Raney nickel. Selectiveoxidation of sec-alcohols.t Raney nickel (large excess)in refluxing benzenecanoxidizesecondaryalcoholsoften in high yield' Addition ofa hydrogen acceptorsuch as l-octene is not necessary.Primary alcoholsare resistantto this The main difficultyis that a largeexcess oxidation,but canundergohydrogenolysis. of Raneynickel is required,but the commercial50% slurry can be used.The main advantageis that the ketonesare readily isolatedby filtration and removal of solvent. Hydrogenolysisof |.r.Jrt-alcohols.2This deoxygenationcan be effected with Raney Ni slurry (Aldrich 507oslurry in water) that has been washedeight times with distilledwater and twice with l-propanol. Thus reactionof a tertiary alcohol with washedRaney Ni for a short time yieldsa mixture of alkenesthat furnish a singlealkaneon hydrogenationcatalyzedby Pd/C. I M. E. KrafftandB. Zorc,J. Org.,5f,5482(1986). r M. E. Kraft andW. J. Crooks, lll, l. Org.,53'432(1988). Rhodium(Il) aceiamide,Rhr(NHCOCHJ, (1). The reagentis obtainedby reaction of Rh.(OAc), with molten acetamide.It crystallizesfrom water as a hydrate.l Stereoselectivetrsns-cyclopropanation.2 Rhodium(Il) carboxylatesare generally the preferredcatalystsfor cyclopropanationof alkeneswith diazoacetates The trans' (7,313;9,406;10,340) even though they show only low trans-selectivity. Use of acetamide. of rhodium(Il) by use enhanced markedly selectivitycan be

sation r silylox. cr,p-um of RhC Exu

CHt.

'A. Ra

Ruttcr N{ pres€n (isolat symme RuC ilinesr 1,2,3. Exa

favorscts-stereoselectivity.l rhodium(II) 2,4,6-triarylbenzoates

Rhr(OAc)a Rh,(NHAc)a

translcis: 3.8:1 translcis-- l0l.l

I M. Q. Ahsan,I. Bernal,and J. L. Bear,Inorg. Chem.,25'260(1986)' rM. P. Doyle, K.-L. Loh, K. M. DeVries,and M. S. Chinn, Tetrahedron Letters,8,833 ( 1987). r H. J. Callot and F. Metz, Tetrahedron,4l,4495(1985).

270

ni catalE

Rhodium(Ill) chloride

I refluxing hr drogen rnt to this tge excess The main amovalof rted with n g h tt i m e s rrr alcohol t furnisha

D\ reactlon d r a t e .' is are gen|z(racetates The transde Use of

Rhodium(Ill) chloride. p-Silyloxy esters.r Silyl keteneacetalsare known to undergoaldol condensation with carbonyl compoundsin the presenceof TiCl (U,268) to afford Bsilyloxy esters.The sameproductscan be obtainedin a one-stepreactionof an cr.,B-unsaturated esterwith trimethylsilaneanda carbonylcompoundin the presence of RhCl.H,O. Example:

o

o

o

.t,t-=A^^,, -l{l- ??>fAo.t, + (cH,)siH -ocHr* c,H,EcH.

c,fr,-cosi(CH,),

T

CHt CH,

' A. RevisandT. K. Hilty, Tetrahedron Leuers.2E. 4809(1987). Ruthenium(Ill) chloride. N-Heterocyclization.t Anilines reactwith 1,3-propanediol in diglymein the presenceof RuCl..3HrOcomplexedwith Bu,P to give quinolinesin 50-60% yield (isolated).Two isomericquinolinesare formed in a similar reactionwith an unsymmetrical1,3-diol. RuCl..3HrOcombinedwith P(CuH5)r catalyzesa reactionof N-substitutedanilines with 2,3-butanediolor 1,2-cyclohexanediol to give 2,3-dimethylindoles or 1,2,3,4-tetr ahydrocarbazoles. Examples:

xc6H4NH2 + Ho(cH,)3oHfffU*r,

?t'

-*,oAI::" xc6H4NHR CH, ae',. 2E.833

271

* zH, @

z-'--2u'

^":;:-#1",,, ($.",

d

Ln

RJ{COTCH:CHr. Vinyl carbamates of thistypecanbe preparedby a RuCl,catalyzedreactionof acetylenewith CO, and secondaryamines.2

Ruthenium(IV) oxide

11"

+ co2+ Hc:cH

dil ri

'fii'nl:*' CH,

$.o,.t:cH,

+

$.o,[tH:cHz

(dt6Vo)

(2Vo)

I Y. Tsuji, K.-T. Huh, and Y. Watanabe,J' Org'' 52' 1673(1987)' 'Y. Sasakiand P. H. Dixneuf,ibid',52,314 (1987)'

Ruthenium(IV) oxide. procedurefor oxidationof alkeneswith NaIOo lr2-Diketones. The Sharpless for oxidationof alkynesto 1'2catalyzedby RuO2$1,462-463)is equallyefficient rate' but ether' epoxide'and diones.In fact, alkenesand alkynesreactat a similar is oxidizedto an acylsilane' estergroupsare stableto the reagent.A l-silylacetylene Yields are moderateto high.' (3' a natural germination The final stepsin a total"synthesisof ( + )-gloeosporone inhibitorofafungus)requi,eaoxidationoftheacetylenegroupofltoadiketone group.TheoxidationwascarriedoutinT4vayieldbythecatalyticRuO2procedure cr-hydroxyl group' the hydroxy of Sharpless.on liberation (pyridine'HF) of the

NalO.,Ruo: cH.cN,ccl., H,o) 14qa

I

.( 't

R fn

to c{

Ruthenium(lV) trifluoroacetate

: H:CHz

n3

diketonegroup spontaneously cyclizesto the hemiketalgroup to provide3 in80Vo yield.' Oxidation of allylic alcohols and enones.s These substratesare cleaved to dicarboxylicacidsand keto acidsby SharplesscatalyticRuO, oxidation. Examples:

NalOa, RuCl.

CH,

ccl., cHrcN oH --- "*-

CH,

rth\aIOo r. ttl 1,2rrrde.and rr l:ilane. rmrnation r drketone procedure c hrdroxY

92%

c(cH3)'

o

I R. ZibuckandD. Seebach, Helv.,7f, 237(19U8). r G. Adam,R. Zibuck,andD. Seebach, Am. Soc..f09,6176(1987). r F. X. Webster (1987). andR. M. Silverstein, J. Ors..52.689 Ruthenium(IV)trifluoroacetate,Ru(OCOCF.),(1). The reagentis preparedln sita from RuO, and CF.COOH. Oxidative coupling of aryl tetahydroisoquinolines.t This reagentis superior to thallium(III) trifluoroacetateor vanadiumoxyfluoridefor nonphenolicoxidative (3). couplingof substratessuchas 2 to provideaporphinesand homoaporphines

cH3o cH3o (CH')"

cH3o 2 , n : 7 , 2 ;R : H o r O C H r I atttt TTFA rr-osz VOF3 rrr-+:z

n4

Ruthenium(IV) trifluoroacetate

lignans'-prestegane Biaryl phenol coupling'z The natural dibenzylbutanolide bisbenzocyclooctadiene corresponding the to A (1a) and B (1b), are converted in 80-8574 yield' The usual lactones(2) by oxidation with RuO, in TFA-TFAA is lessefficient(45-50Vo reagentfor this oxidation,thallium tris(trifluoroacetate)' vields).

S Sr

( Smo doub

cH3o

genct

RuO:,TFA, TFAA, CH,CII,

)

Er

80-ESCI

OR2 1I,Rr:CH3,R2:H lb,Rt=R2:H

oR2 2

(1987)' ,y. Landais,D. Rambault,and J. P. Robin,TeffahedronLetters'2t' 543 (1988)' 'i.-p. nutin and Y. Landais,l' Org',53' 224

rG./

Sr

, SmC for d but c

Pfe\tegane x\_ladiene The usual r tti-5j7o

H

V-\ l /\ H

o

r't

D SamariunpMethyleneiodide. Cyclopropanation.t The carbenoidobtained from the reaction of CH'I, with Smor Sm/Hg in THF effectscyclopropanation of allylicalcohols,but not of isolated double bonds.The reactionof both cyclicand acyclicallylic alcoholsproceedsin generallyhigh yield and often with markeddiastereoselectivity. Examples:

b OH Sm, CHrlr

0"

.\

92Va

(/

'' -*T\dJ.*T>* ;r:.t'J 7 : l. 4 >200:I

99Vo 88Vo

R = Bu R = iPr

OH Sm/H8,CHTCHI, l$9o

\-/ (exo)

(endo)

I G. A. Molander and J. B. Etter, J. Org.,52,3942 (1987).

Samarium(Ill) chloride. Lewis acid catalysis. Anhydrous lanthanide(III) chlorides, particularly SmCl, can function as low-costbut efficientnonhomogeneous Lewis acid catalysts for aldol and other reactions.More rapid reactionsare observedwhen the soluble but expensiveEu(fod), is usedas a lanthanidecatalyst.'

275

n6

Samrrium(Il) iodide

Sub stin

ExamPle: /ocH' (cHt'c:c-osi(cH.)l --- I *"" srct,.cH,cl).2f t

C6H5CHO

;-

(cHr)lsicN I ggqo SmClr,CHrCl, I

?n'

C6H5_CHCN

osi(cH3)3 c6H5-cHc-coocH, t l HO CH3

8, 5513(1987)' Leuers, I A. E. Vougioukasand H' B' Kagan' Tetrahedron

Samarium(ll) iodide. powder by reactionof 12with samarium Preparation.SmI, can alsobe prepared with reaction further of SmI' is formed' which on and THF. A yellow suspension SmI2'' the metal under reflux is convertedinto SmI' can promote intramolecular reducreduction' Intramolecular pinacol to provide2'3-dihydroxycyclopentanecarboxylates tive colpling of keto atOetryOes with markeddiastereoselectivity'2 ExamPle:

rc Sml' THF. CH,OH

CH,

OC2H5 -

,-"'

oHc Allenicalcohols.llnthepresenceofSmlzandPd[P(CoHs)Jr'sec-andtert. p r o p a r g y l i c a c e t a t e s a d d t o k e t o n e s t o g i v e a l l e n i c a l c o h o l s a s t h efrom o n l y reormajor alcohols is formed p.olu.i. A mixture of allenic and homopropargylic actionsof primary propargylic acetates' ExamPles:

+ (cH)2c:o 31Hgt nco(cHJefHC:cH

o'ott" lrt:c:c(:,

OAc

C:CH OAc

obti and ! ketr cen

q::.

.Go_;*

tc",), OH

ofF to

Semarium(ll) iodide

m

Barbier-type cyclization of u-(a-iodoalky t) _p_keto estersor arnides. Substances ofthis type (la or rb) cyclizein the presenceofSmI, to crs-1,2-disubstituted cyclopentanes or cycrohexanes (equationI). Similar diastereoselectivity

? /r\ \',,

3

R^/\ | |

(Y

HecoY ,r',,. R'.'.!....H ,-i'i / \,'/

\

+

.,n

cis-2

la,n = 1,2,Y = N(CH3), lb,n=1,2,Y=OR,

OCzHr

2 smrr 70-mEo

rJcr lr rlh

trans_2 >2oo:l

H? gooc,Hs R...h.R' +

\.2tl

/

\

2.2U,:t )a

CHt

riue l.rtc.

s cooc2H5 uo..../--{....n' CH,

cis4

HO cooc2H5

lcc,H. CH.

92Eo

cH, n

cHr

HO goocrHs

,

cH,.H...gr,

5

i.' r !' ldl(rf

n rc-

obtainsin cyclizationof substratescontainingan alrylic haridegroup, such as 3 and 5.a SmIzalsoeffectsan intramolecularreductivecoupling of certainunsaturatedB_ keto estersor amidesto cyclopentanes with good stereochemicar controrat three centers(equationII).s

3

Hocoy

p

cH''H n

(rr) *A#:ll-H,r I

H.€\/

cH,' \'/

Y = OCzHs,R = CHt 75Va y = N(CH3)r,R= H jBVo

25:l >200:l

Asymmetric in tramolecurar Reformatskyreac tions.6 The bromoacetates(r) of p-hydroxyketonesundergoa Reformatsky-type reactionwhentreatedwith sml, to give B-hydroxy-6-vareroractones (2). These productsare usefurin their own

nE

Samrrium(Il) iodide

Ra

o il

nrcHz\

2 Smlr, THF

q

este6 ll increrq dimethl esters ((

CHTNHT

"-C,HMC,Hs la, Rr = H, R' = CH: b, Rr = CH3,R2 = H

86Vo 977o

88Vo 94Vo

2 ( 1 31: )

gH 9y.c,H,

,-c,HfficoNHcH3

(r) cH

retentio

9.^v-um 3 syn-l'3-diols(3)' The exampleshows right, and are alsousefulprecursorsto acyclic observedeven with the diastereomeric that the syn-l,3-asymmetricinduction is caseof lb' in which the ct-substituent pairsln and 1b, althoughit is diminishedin the assumestheaxialorientationinthelactone.Thesamel.,3-asymm etricinduction However' the oppositesnti'l'3obtainswith derivativesof p-hydroxyaldehydes' keinvolving a '-butyl p-hydroxyalkyl induction has been observedln one case tone (4).

o ll

BTCH2C-

? ?

25mI,

.C(CH,),

88Va

(

Mag selectiw iodohyd overallr Rd (E)-ally are redl Exan

OH

c.H}fc(cH,), CH, 5

be obtained by intramolecular reBicyclic 1-lactones.l These lactonescan with SmI' in THF-HMPT' ductive cyclization of unsaturatedketo esters Example: A

smr,,THF

tl _BInd(cu,)ocH:cHCoocuH, R=CHr R = H

66Vo 34Vo

translck = 70:30 " = 70:30

Dil modeor 1,3-dig

Samarium(Il) iodide

ng

Reduction or s'tp'epoxy estersto p-hydrory esters.t SmI, alone reducesthese estersto a mixture of q- and B-hydroxyesters.The reaction rate and yierd is increasedby additionof HMpr. eaoition of a cheratingagent,TMEDA or N,Ndimethyraminoethanol (DMAE), resurtsin regioserective reductionto B-hydroxy esters(equationI)' The systemreduces opticaliyactiveepoxyesterswith comprete

;il,'ilyfil

.o

(r) cHi(I-cooc2H. #

9H

cH1-\-cooc2H5 '

+ cHi-\-cooc2Hs >2(fr:r

CH

6ff

retentionof configuration.It alsoreduces vinyrogous epoxyestersto (E)-6-hydroxy_ B,"y-unsaturated esters(equationII).

O'A \

rna !e nI

(II)

QH

-o

cHSI-\.-cooCHr

;;

(6-OH/1-OH = >2ffi:t)

ltLrn

L-rke-

.r/',,2,,..-coocHj

Magnesiumiodidereactswith c,B-epoxy estersto form B-iodo-a-hydroxy esters selectively(200:r). The regioserectivity is uttribut.d to favorabrecherationof the iodohydrin.Theseproductsare reduced by Bu.SnHto a_hydroxyestersin 75_95Vo overall yierdswith retentionof the originar configurationat the c-position. Reduction of vinyroxiranes.e The substrates are reduced rapidry by SmI, to .-(E)-allyticalcohorswithout effecton keto, ester,or nitriregroups.chiral substrates are reducedto opticailyactivearcoholswith compreteretentionof stereochemistry. Examples:

6''"'*d:'"'

r reCtH,'.

orH +

coocrH.5 (957o ee)

** c,Hi,r1 \-ctl,cooc,tl, (95Vo ee)

Dihydrofurans.to Dihydrofuranscan be obtained by reactionof o,o-dibromodeoxybenzoin(1) with sml, and an alkene. The reaciionevidentlyinuotu", u 1,3-dipolaraddition of a ketocarbenoid to an alkene.

Samrrium(ll) iodide

C"H. - --cBr,

C^H, - "\--

CH,

Smlr, THF, HMPT

tl + CH ---6%-

l .C:o

I

/

\

CuHt

CuHt-

, T .h

CuHt

QH,

1+ cH2:cHC:cHzd

:G.rl

h-a", CuHrloACH:CHz

of carbonylcompounds 1-Lactones.rt SmI,promotesreductivecross-coupling catalyzesthe rate of HMPT in resulting esters 1-lactones. with c,p-unsaturated this reactionmarkedlY. Example:

G..

0 ) l

cuH,4olcu',

CH. \

/ /-\

H'

srl,. rHr HocH(cH,),

CH. '

coocH3

s7%

qY;

Medium-ring lactones.D Lactonescan be obtained by an intramolecular Reformatsky-typereactionof o-(bromoacetoxy)aldehydesin the presenceof Sml' ' The p-hydroxylactoneswere isolatedas the acetates.Yields are high even for 8lactones. to 14-membered

ot l tl

oHc(cHr)"occHrBr n = 4 =10

l ) S m l , ,T H F , 0 ' 2) AcrO, DMAP)

76Vo 92Vo 84Vo

]T.T .G.A

5G.A 6G.A 7S.Fu

(r9E 'K.O ,G.A ',,S. Fl

ilK.O jinan I: T. TI ( l!186 rr J. Itu 'tK.q

Srllri q.t

ketonc dehydc

Exe

(9H,){oA'

6Y' o

'M. M.r HM|T catalysis,t3SmI, alonecan reduceprimary alkyl bromidesor iodides of in high yield, but the reactionis slow even in refluxingTHF In the presence are chlorides, HMfT (-5 mole Vo), alkyl, aryl, and vinyl halides,and even alkyl reducedin almostquantitativeyield at 25" often in lessthan I hour. The combinationof SmI, and HMPT effectsa Barbier-typereactionof o-bromo esterswith carbonylcompoundsto provide 1- and 8Jactones(equationI).'a

Selenir

tra

a seleno a symlx

Selenium

o (I)

tl

SmI!,

C6t{s(cH2)ricHr + Br(CH2)"COOGH" rHF.HMP')

CHr>aroa.ooo

85vo C6H5(CH,)i L,Jn,r"_,

n = 2 n = 3

55Vo

I T. Imamoto and M. Ono,

mS.runds e rate of

,o 11, rular Re; trf SmI2. ren for 8-

Chem.Letters,501(19g7). : G. A. Molander andC. Ke.nny, t org., ii,'2tiii,sssl. 3T. Tabuchi, J. Inanasa. anaM. vama!;;r.' Z;;'. Letters.227s (1987). rG. A. Mofander, J. E. E_tter, andp. rii. ii;;;:";m. soc.,r0e.4s3(1e87). 5G. A. Molander andC. Kenny,Tetrahedron'-ie'i'^,lS, 4367 (lgg7). 6G. A. Molander andJ. B. Etter,A^. i;;. ,-16;,'Ziro usz;. 7S.Fukuzawa, l M. Iida,A. Nakanishi, T. F"ji;i,;;d S.Sakai, J.C.S.Chem.Comm..9z0 ( le87). " K. Orsubo,J. Inanasa. andM. yamaguchi, Tetrahedron Le,ers,8, 4435,M37(1gg7). " G. A. Molander, B.-E.LaBelle, ""0 b. Hrf,",i. Org., 5t,5259 (1986). r"S. Fukuzawa, j.C i." T. Fuiinami, andS. Sakai, Cir*. Comm.,9l9,(1987). " O,,.r*o:J..Inanaga, andM. yamag""ni,in^ira*n Letters,27,5763(1986); f: T. Fu_ ;inami,S. Sakai,andA. Nakanishi, J.b.S.Che;.'iomn.,624(1986). ': K. Kawamura,J. Inanaga,unafr'. Vurug uchi, TeiahedronLetters,27, 38'g I#iuchi, lr J. Inanaga, M. Ishikawa, andIVl.yamaguchi, Chem.Letters,14g5 (I9g7). 'nK. Otsubo, K. Kawamura, J. Inanaga, u'nO f*if. V"ra .*hi, ibid., l4g7,gg7\.

Samarium(Il) iodide-1,3-Dioxolane. a-Hydroxy ardchydes't A solution of SmI, in l,3-dioxorane reacts with . a ketone and iodobenzeneat room temperature to form a protectedc-hydroxy aldehydein about 75vo yierd.The reaction r"y inuotu. a 1,3-dioxolanylradicar. Example:

o ll

BzICHTCCH. +

-z/\.

Or

L_J

or rodides rerenceof )ndes,are ( --bromo It '

Smlr, C6H5l,

-O t

-

CH,CN.HMpr

nqa

'€

f M. Matsukawa, J. Inanaga, andM. yamaguchi, Tetrahedron Letters,2E,5g77 (lgg7).

Selenium. with wittig rcagents. selenium reacts with wittig reagentsto form leactign a selenoaldehydeor -ketone, which reacts further with the wittig reagentto give a symmetricaltrans- alkene.t.2

-

82

Silvertrifluoromethrnesulfonale

Example: I

(C6H5)3P:CHCOOCH3* Se -

[Se:CHCOOCHI

I (C6H5)3P:Se+ CH3OOCCH:CHCOOCH: (77Vo)

Bd(

Q4Vo)

give RCH: Since (CuH,).P=Sealso effectscleavageof (C6H5)3P:CHRto provides version this amounts; catalytic in used cHR and (c6H5).P,seleniumcanbe alkene' the of forms geometric the thermcdynamicmixture of the

. P (t9

l K ' O k u m a ' S . S a k a t a , Y . T a c h i b a n a , T ' H o n d a ' a n d H . o h t a , T e t r a h e d r o n L e t t e r s , 2 S , 6 6 4 9 Sir (1e87). pan 'd. nit"t, R. Hock,andR. Nolte,Am. Soc',110' 624(1988)' a lir orr1 resp Serine,HOCHTCH(NH:)COOH' in two prepared be can acids is cr pure amino Optically Amino acid synthesis.r of Reaction L-enantiomer. or oclea the either as available stepsfrom serine,readily to rl N-benzylserine(orofN-benzyl-N-Boc-serine)withthepreformedMitsunoburealmost (2) in serine protected P-lactone the provides agent i; CH.CN at 55' (R,CuLi) to qirantitativeyield. The lacione reactswith lithium organocuprates

.Jftl3. qH,oH -:::::+

."J,tt8l,n,f" ? --4y83%'

"1

BZINH

COOH

BzIHN, 2

.b

?"'*

gzIFINACOOH 3 (99Vo ee)

yields. providethe desiredbenzylaminoacids(3) in moderatechemicaland optical cul, which The bestresultsare obtainedby useof Grignardreagentscatalyzedby reactwith almostcompleteretentionof optical purity' L' D' Am' Soc"lW'4649(1987); lL. D. Arnold,J. C. G. Drover,andJ. C' Vederas' (1988)' ibid',110'2237 Vederas, C. J. and Arnold,R. G. May,

ii

ri,

$

$

d

Silver trifl uoromethanesulfonate. chloride I c-Glucosidation.t Reaction of the protected c-o-glucopyranosyl ketones' or esters with silylenolethersactivatedwith AgoTf resultsin c-c-glucosyl

( CH

SimmonFsmith resgenl

Example:

.cl *

'OBzl

)OCH. I

l('H = frr\ ldes

It

r,619

I rn trvo fl!rrO Ot t\)l-\tl fe-

r .rlmost lut,r) to

R o()H c

ai r relds. rl. which

r'

L. D.

hloride 1 'i.cttlnes.

CH2:QQ^ll. |

...cH2coc6Hs

AgOTf. cHrcl: I 88qo

"OBzl

osi(cH3)3 2

I P.Allevi,M. Anastasia, P.Ciuffreda, A. Fiecchi. andA. Scala. J.C.S.Chem.Comm.,l0l ( 1987). SimmonrSmith reagent. Angular methylation. In a generalsynthesisof limonoids,Coreyet al.t preparedthe tetracyclicenone1, which lacksonly the angularmethyl group at crr of a limonoid.2Conjugateaddition of a methylcopperreagentto I fails, probably owing to sterichindrance;however,the Simmons-Smithreagentaddsto the corresponding16o-alcoholto givea singlecyclopropane(2) in89vo yield.This product is convertedinto the limonoid 3 by oxidation to the ketone (pDc) followed by cleavageof the cyclopropanering with Li/NH.. The samereactionswhen applied to the l6p-alcoholcan be usedto introducea p-methylgroup at C,..

N

Sodiumbenzeneselenolrte

11)9'918 (1987)' I E. J. CoreY,J. G. Reid' A' G' Myers, and R' W. Hahl, Am' Soc'' (1984)' : D. A. H. TaYlor,Prog' Chem' Nat.Prod.,45' 1

Sodium amide. cis.SelectiveWittigreactions.Schlosseretal|havereviewedexperimental with reactions' The ylide is best generated details for effectingcis-selectiveWittig or lithium of Jn ethereal solvent at 25". use sodium amide (free trom-Naorr) in potassiumbis(trimethylsilvrl"miaelowerstheyieldandthecis.selectivity.Solvents or t-butyl methyl ether' The.carbonyl of choice are THF, ethylene glycol' ether' the slowly and with cooling to maintain compound should be added tlo the base 25"' is then completedat temperature^t -75" to 100'' The reaction groups tt":-":"^:::"trialkyl by group :'::: Replacementof the triphenyl groupscan lncreasec'rphenyl customary the of bulk the in increase but tectivity, as 125-tn\is recommended selectivity.Tris(o,o'-difluoropi"nyf)pftotphine.(m'p' particularly in cis-selectivewittig reactions, a replacementfor triprrenlp't orpirin" of aiomatic and o,p-unsaturatedaldehydes'

,M

:v

13

Soa

(C, mal

rM.Schrosser,B.Schaub,J.deoliveira-Neto,andS.Jeganathan,chimia,4o'244(1986); ibid''q'246(1986)' andM' Schlosser' S. Jeganailran, B. Schaub, Sodium benzeneselenolate' preparedby two methodsfrom diphenyl Preparation. This reagenthas been methodinvolvesreductionwith NaBHn diselenide.The originalunitott common inethanol(s,272)'AnewermethodinvolvesreductionwithNainTHF(t,44.|). Actually,thefirstmethodresultsinasodiumphenylseleno(triethoxy)borate'Na* for some reactions' Although either reagent is satisfactory [CuHrSeB(OCrH,)r] ' of c'p-epoxy ketonesto p-hydroxy only the boratecomplexis usJfulfor reduction to uncomplexedNaSecoHsprovidesa ketones.However, addition of B(ocrHr), l)'r reagentthat is equallyeffective(equation

(t) *-99: l)

3V2

Thrlium(Ill)nitrrte

Sincethestartingmaterialsareavailablebyreactionofaldehydeswithlithiated vinylethers'thissequenceisusefulforconversionofaldehydesintothesetriols. active glyceraldehydeinto Indeed this sequencecan be usedto convert an optically optically pure pentitols with high sytt-stereocontrol'

Bd

rK.Tamao,T.Nakajima,R.sumiya,H.Arai,N.Higuchi'andY'Ito,Am'soc"lot'6090 (1e86). (1988)' 2K. Tamao,Y. Nakagawa, H. Arai, N. Higuchi,andY. Ito, ibid''ll0' 3712 3L. N. LewisandN. Lewis,ibid',LM,7228(1986)'

2,2,6,6-Tefi amethylpiperidinyl'l'oxyl' can be '' -ino @f',12,479-480)' This oxidation oxidation of -CIIQH effectedinhighyietowithsodiumhypochlorite(slightexcess)inbufferedH,o/ The oxidationis exoCH2CI,with this nitroxyl radicaland KBr as the catalysts'r 0-15" with a salt-icebath' thermic, and the temperatureshouldbe maintainedat in88-93Voyield; yieldsare Saturatedprimary alcoholsare convertedto aldehydes lowerinthecaseofunsaturatedsubstrates.Additionofquaternaryoniumsalts permitsfurther oxidationto carboxylicacids'

c

metl

rp.L.Anelli,c.Biffi,F.Montanari,ands.Quici,l.org.,52,2559(1987);P'L'Anelli'F (1988)' andS. Quici,Org. Syn',submitted Montanari,

(PraN)RuOa(1)' Tetrapropylammoniumtetraoxoruthenate(Vlfl)' of RuOr with PrNOH in reaction by solid green a fne realent is obtainedas aqueousNaOH. SuPPlier:Aldrich' N-oxide Catalytic oxidant.t In combination with N-methylmorpholine as a used compoundcan be (7,244)as the stoichiometricoxidant, this ruthenium in yield or ketonesin high catalyticoxidant for oxidationof alcoholsto aldehydes generallybeneficial.Racemization cHrcl2 at 25.. Addition of 4A molecularsievesis iSnotaprobleminoxidationofalcoholswithanadjacentchiralcenter' Tetrabutylammoniumperruthenatecanalsobeusedasacatalyticoxidant,butthe preparationis lessconvenient' andA. D. White'],C.5. Chem,Comm.,1625 l W. P.Griffith,S. V. Ley,G. P.Whitcombe, (1987).

Tlcr

I

tem sodi Red rH.

Ttr( Thallium(I[) nitrate ('ITN). of cyclic alkenes Ringcontraction o! glicak'r The oxidative ring contraction the o-glucal I of oxidation Thus glycals. (4,4g2_4g3)can be "p;li; to protected 2' whosestructurewas with TTN in CHrCN providesthe 2,5-anhydro-D-manose establishedbyconversiontothe2,5-anhydro-n-mannitolderivative(3)'

( reac hydr the r med

Tin(II) bromide

I ltthiated :sc triols. hrde into

BzlO

BzlO cH1cN,25'

NaBHr

CHO . lm. 6090

62% from I

8\l

on canbe lred H:O/ on is exo-rce bath. r r e l d sa r e nrumsalts

cH2oH OBzl 3 Oxidation of 3,4-dihydro-2H-pyran(4) with TTN in CH3OH provides2-(dimethoxymethyl)tetrahydrofuran 5 in essentiallyquantitativeyield.

. {nelli, F. +

lr.\OH in e N-oxide I usedas a igh vieldin cemization ral center. rnl. but the

."H rt /

\ r(noi \o/-cHtocH,):

lA. Kaye,S. Neidle,andC. B. Reese,Tetrahedron Letters,29, 1841(1988).

ThexylchloroboraneDimethyl sulfide. RCOOH --->RCHO(12,485).' This borane (2 equiv.) reducesacidsat room temperatureto thexylboronicacid and aldehydes,which are best isolatedas the sodium bisulfiteadduct. Yields of aliphaticaldehydesare in the range80-95Vo. Reductionof aromaticacidsis slow, and yieldsare significantlylower.

)onrrn., 1625

rH. C. Brown,J. S. Cha,N. M. Yoon,andB. Nazer, (1987). J. Org.,52,5400

circalkenes l o-glucalI ructurewas

Tin(II) bromide. a-Methyleneketones.t In the presenceof SnBrr, bromomethylmethyl ether reactswith silyl enol ethersto give c-bromomethylketones,which undergo dehydrobrominationwith DBU to give o-methyleneketones.Higher yieldsobtain if the overall reactionis conductedin CHrCl, at 25'without isolationof the intermediate.

)

Tin(lV) ciloride

* t"'\f"' ..t{;')''"'on'"'u''' [.."\:*"'l o

d

osi(cH3)3

l) Lic(scrH,), 2) cls(cH,)3 )

l) CH'OCH1BI. SnFl

2,) D B U

TOVo

\

/

o '

/>,n, L\tsc.n,l,

t(scuH'),

' M. HayashiandT. Mukaiyama,Chem'Letters'1283(1987)' I

tr Tin(IY) chloride. can be obtained in Rearrangementof allytic acetals' 3-Acetylpyrrolidines The of 5-methyl-5-vinyloxazolidines' goodyieldby an acid-cat'uiy'ed'"u"ungement cycliMannich by followed rearrangementinvolves an aza-Coperearrangement zation(equationI).1 CH,

(r) H,cz\koH I

\NH,

CH, n*ro H2Cz\-'{--o1 | )-R \N, H

ICH,>,"scH, I HO-l

I

L

\tl^* H

4

a*t:?l A;zcH'

R

H

I I

fr

H'

/cocH3

, f 1

-so-1oq"

R{N/ H

ArelatedLewisacid-cata|yzedrearrangementprovidesasynthesisoftetrahymaterial(1) is preparedby reactionof drofuransfrom allylic acetals'lThe starting followed by acetalizationof ketone with vinylmagnesiumbromide' an cr.-hydroxy exposureto C'H'AICL or SnCL at the resulting diol with un uiO"f'yO"' On in baseto the -lcF>-10', I rearrangesto the all-'i'-produ"t 2' which rearranges of rearrangewith no loss enantiomeric epimer (3). Optically activeallylic acetals followedby may involvea hetero-Coperearrangement purity. This rearrangement pinacolrearrangement' an aldol or a Prinscyclizationand then a

n n z p i!

c

t(

t u

Tln(tV) chtoride CH3-

CH,

l) cH::cHMsBr V,,O 2) C"H,CHO I r _ - - - - - - T ] '1-/o -

cHiou

3tXt

cH. sncL /cocH3 H,cA{-Q -70+ - lf ./ \ I FcuH, 58% cuui\oAcH, cH-o I

L

2

lo"

n

..cocH3

cuHiolcH,

H ,) :

3

arnedin nc'..The

This rearrangementof alryricacetarscan arsobe usedfor furan annerations,in which the formation of the new tetrahydrofuran ring is coupled with ring enrargement of the starting ring.3 The same cis-fusedbicyclic tetrahydrofuran is formed from either one of the cr,s-or trans-allyricdiols used as starting materials.

ch cvclia'l

l) CH::CHMgBr 2) CH,CHO

OH

SnCL,-70"

locHl

rctrahyaction of z.ttlon of SnCl. at sd to the Itl()meric Itru ed by

cyclization of mired acetals (13,300).1 This reaction is a particularry useful route to eight-memberedcyclic ethers (oxocanes)and provides the first practical route to a natural oxocene,(-)-laurenyne (3), from an optically active mixed acetall. Thus cyclizationof I followed by o-desilytation afiords2 as the only cyclic product.Remainingstepsto 3 involvedc-desilyration,for which only HF/pyridine is useful' introductionof unsaturationinto the clside chain,and eitensionof the cr-sidechain' Exploratorystudiesshowedthat unsaturationat the por 1-positions to the cite of cyclization of L prevent or retard cyclizationwith a wide variety of Lewis acids. The cyclizationis apparentrymore torerant of substitution in the terminatorposition,Cr-Cr, of the oxocene.

Tin(II)

(cH3)3si

cl (cHr)3si\ /,/--\...' l s l

8n, )

n-d \OC,H,

Ocr Thc I

1) SncL 2) BUaNF

'cH'ors

3'lEo

CHroTs HO(CH,)3

R.SiO(CH,)i

CrH

.cl "".r'1r'C-CH

F

CH, (-)-3 M. E' okazaki,andG. P. |leier,Am. Soc.,|05,6622 lL. E. overman,M. Kakimoto, (1e83). 'it4. ff . ffoptlnsandL' E' Overman'ibid"ltg' 4748(1987)' J' Org'' p. tairnru,M. J. Brown,andL. E. Overman, r p. M. Herrinton,M. H. H;;il, s 2 , 3 7 1 (11 9 8 7 ) . Am' Soc''110'2248(1988)' 'f-'g. Ou.r.un andA' S' Thompson' Tin(IV) chlorideZinc chloride' preparedby reaction of acetalswith Propargylic ethers.t Theseetherscan be Lewis acid suchas in the presenceof at least 1 equiv' of a 1-trimethylsilylalkynes ZnCl2(10 mole % and SnClo of TiCL or SnClr(12,375).However a combination may be *SnCl'catalyst actual The each) can effect this ..*ion (equationI)' -ZnCl,.

dc(

FI thc

sncl,ZnClz ?tt'

* cH,c-csi(cH3)3 -#(r) RCH(OCH3)2

Ris-c:ccH'

lM'Hayashi,A.Inubushi,andT.Mukaiyama,Chem.Leuers,l9T5(|981).

r

:,1

Tin(II) trifluoromethanesulfonate' of the chiral diamine (S)-1Asymmetric sulfenylation't In the.presence reactwith

of ketones 1i)' tmlrr;enolates methyl-2-(pip"tainvr*iiiiijfvnoridine

1-t)l'"'H \-'.f CHr

\J

)

rr

A ni' rh to prr

Titanium(Ill) chloride-Lithium rluminum hvdride

T:

phenylthioarenesulfonates to provide B-ketosulfideswith high enantioselectivity. The productsare usefulprecursorsto chiral epoxides. Example:

o

sn(orfh.r

ll

3:#{\ cuHricHrcH3+ c6H5ssorc,,,H,

o tl c.Hi\-CH'

DIBAH'

I sc6Hr

(85Vo ee)

OH t .v o ''tA-t,-CH' r) I SC6H5 (8:l)

I A J

c.H,f-\cH., (R)

1-rri rth u.h.ts

Glycosidation (13,302). Glycosidation of 2-acetamido-3,4,6-triacetyl-2deoxy-ct-n-glucopyranosyl chloride(l) mediatedby Sn(orf), providesexclusively The most satisfactorybaseis 1,1,3,3-tetramethylurea, B-glycosides. and cH,cl, is the preferredsolvent.2

oic'. in(l-

OAc ROH Sn(OTf)'

AcO AcO

fi-85%

AcO AcO

I lT. Yura,N. Iwasawa, R. Clark,andT. Mukaiyama. Chem.Leuers,lg09 (19g6). ' A. Lubineau, J. Le Gallic,andA. Malleron, (19g7). Terrahedron Leuers.?a,5041 rSt-l:! \\lth

Titanium(Ill) chloridelithium aluminum hydride. Reductive elimination of an allytic diol group. A new synthesisof vitamin A involvesreductionof the allylic diol I, preparedin severalstepsfrom B-ionone, with a low valent titanium formed from Ticl, and LiAlHo in the ratio 2:1. Thus, the allylicdiol groupof I [either(E) or (z)] is reducedto an (E,E)-1,3-dienegroup to form the silyl ether (2) of vitamin A.r when the primary hydroxyl group is protectedas an acetate,the reductiongivesa mixture of (E)- and(Z)_2.

fi trnium(Ilt)ctloride-Potasslum

/ Graphite

cHrosiR3

kctr 'l of ard

,4. 1(E and Z)

TI

,r" ,r* r,.,,,.,o,rr, f

to( plir

glvt

tol

Thisreactionwasalsousedinasynthesisofl3-cir-retinoicacid.zThusreduction triethylsilyl ether (4).of 13-cis-retinol' of 3 under the same .ondition5,gives the double bond' This product can be with retention of tfre geometryolthe terminal and oxidation (60Voyield)' converted to l3-crs-retinoica"iO by deprotection

(C'H'),

**

Ilfitlll'"'('

osi(c2H5)3

Lettell'!t213 (1988)' rG. Solladid andA. Girardin,Tetrahedron (1988)' 'G. Solladid, A. Girardin,andP' Matra'ibid"zft' 20S TiClr / C'K ( 1 : 2)' Titenium(Ill)chloride-Potessium/ Grephite' with CEKat 150-160"providesa finely McMurry coupling't ReactionoitiCtt which effectscoupling of aldehydesor dispersedform of the metal on graphite'

(:

Titrnium(IV) chloride

:m9

ketonesto alkenesin generallyhigh yield. A relatedreagentpreparedby reaction of TicL with csK at 0ocan effectpinacol reductionof aliphatic aldehydesor ketones and effectsMcMurry coupling of aromatic aldehydesor ketones' I A. FiirstnerandH. Weidmann, 1071(1987)' Synthesis'

Titanium(lll) chloride-Zinc/copper couple. Dicarbonyl coapling(8,483). This Ti-catalyzedcouplingoffersa usefulroute suchas humulene(4).'The precursoris obtainedby couto cyclicsesquiterpenes pling a vinylic zirconiumcompound(1) with the n-allylpalladiumcomplex(2) to yield. This product couples live, after deprotection,the keto aldehyde3 in 84Vc yield. in 60Vo isomer single to humuleneas a

QH.

cllon Inol. tn be

(lH3o)rcH

QH,

* .rf* zrCp2Ct f-cH:cH Pd

l) cH,cl?

3 x8-(CH')'COCH. " MVo

CH.

,

I

3

,,*l;,J"J CHr

CH, 'CH,

4

I J. E. McMurry,J. R. Matz,andK' L. Kees,Tetahedron,43, 5489(1987)'

a hnelY ;rdesor

Titanium(IY) chloride. lr2-Reanangementof epoxy silyl etherc.t When treatedwith 1 equiv' of TiCL' c-silyloxyepoxidesrearrangeto p-hydroxycarbonylcompounds'

310

Titenium(lV)chloride

Examples: o,-,.r

PSi(cH3)3

vx^' I cit' coHt

=*-s

CH,

aldr ao( I

o H o

ricrl.

I

II

cH5fcH, CuHt

QH

?Si(CH3) r)ricr. CH, z)ss(c,n,),, 35Eo

C"l

C,Hf\CHZOH

.nlcu,

CH,

Aryl and alkenyl groupsundergothis cnfi-migrationmore easilythan an alkyl in combinationwith Sharplessasymmetricepoxidation group. This rearrangement route to aldolsand 1,3-diols(secondexample). affordsa stereocontrolled This rearrangementcan also be effected with catalytic amounts of either (CH.)3SiIor (CHr)rSiOTfin the caseof a,B-epoxytrimethylsilylethers.Yields are dependenton the migratoryaptitudeof the group that rearranges'2 Intramolecular cyclizationl enolate trapping of allylsilanes (cf., 12,4964g7).3 The intermediateenolateformed in the TiClo-catalyzedcyclizationof 1 can be trapped by chloromethylmethyl sulfide to give a decalonederivativewith a potential methyl group on the angularposition. Actually the reactionresultsin

,K An :K rT. .M

TA

CHt

CH,), TicL,clcHrscH. cHrclz,o'

..CH, ..CH,

+

77Vo

frol ofr l

I

CHO

2cHo

".CH,

'c high yield of a singledecalonederivative(2) in which the four contiguoussterditerpenelineogeniccenterscorrespondto those presentin the cis-chlorodane aridial (3).

Th

lao

Titrnium(IV) isoproPoxide

311

p-Chloro corboxylic acids.4 The condensationof ketene silyl acetals with aldehydesmediatedby TicL (Mukaiyamareaction, 6,590) resultsin B-hydroxy acids. use of 2 equiv. of Ticl4 resultsin p-chloro acidsin 70-90vo yield. Example: [

I c6H5cHo* cH3cH:closi(cH3)31,

9Si(CH3)3

tcr"

la."\ZcooH CH,

oricr" " I

alki I all(1n

xlhcr b,rrc ,-ltl h

I s'tn

-l '

cr

p o o H +-T i o C t ' -,c.H5fcooH | 8G.."ry'\r\rn , CH, CH,

' K. Maruoka,M. Hasegawa, andG. Tsuchihashi K. Suzuki,M. shimazaki, H. Yamamoto, Am. Soc.,108,3827(1986). ' K. Suzuki,M. Miyazawa, 3515(1987)' Letters,2E' andG. Tsuchihashi,Tetrahedron 3T. Tokoroyama, T. Asada,andH. Iio, ibid.,2t' 6645'(1987)' M. Tsukamoto, 1M. Bellassoud, ibil.,29. 1275(1988)' J.-E.Dubois,andE. Bertounesque,

r'r:h J rl!. ln

Titanium(IV) chloridelithium aluminum hydride. Reduction o! enedicarhorylates.t A low-valent titanium reagent obtained in the presence from TiCL and LiAlHn (about 2:1) can reduceenedicarboxylates of a trace of triethylamine. Examples: Ticl., LiAlH., N(czHrh

qH'OOCCH:CHCOOC'11, -m,!*tr..--

C2H5OOCCH2CH2COOC2H5

fu;x''-&o..", coocH3

'C. W. HungandH. N. C. Wong,Tetrahedron Leuers,8,2393(1987)'

t\ rlcr:na lln-

Tiienium(IV) isopropoxide. Lactamilation.r In the presenceof this reagent,o-amino acids cyclize to lactams.Yields are 75-93Vofor cyclizationto 5- and 6-memberedlactams.

lt2

Tributyltinhydride

clear than worl

Examples: 9H'

ri(o-j-,,)..

rntcHt

t*#": H,N(cH,),CHcooH

c

("\

ofn inte mok

H

CH3NH(CHr)TCHzCOOH ;

t

\N.A

I

l

I

qcli hldr Thu (0.1

o

CHr (1988)' I M. MaderandP. Helquist,Tetrahedron Letters,29,3049

2,4,6-T!i-t-butYlPhenYllithium. Thisbase(1)ispreparedbyreactionof2,4,6-tril-butylbromobenzenewithBuLi in THF at 0". lithium Kinetic enolates. Alkyllithium reagentshave the advantageover alkane a neutral is amides for deprotonation of ketones in that the co-product abstraction ratherthan an amine.This bulky lithium reagentis usefulfor selective enolate' ct-protonof ketoneswith generationof the less-stable of the less-hindered Thus as shown previouslyfor a hinderedlithium dialkylamide(LOBA'12'285)' mainly results reactionoi benzylmethyl ketone (2) with 1 and ClSi(CHr).at 50o much more in the less-stableenolate (3), even though the benzylicprotons are

stoK eoc( F l ofr .CH ils r dou

acidicthanthoseofthemethylgroup,thelesshinderedones.Mesityllithiumshows

o'ii

I. CIS(GH,),. ll THF.-sr C6H5CH2CCHtn%-

,

C6H5CH2-)C:CH2 TMSO' 3

+

" ').:.1

CII.

74:26 H'

CH.

brus

4 (ElZ -- 2:l)

use of LDA resultsin formation of 3 similar but lesspronouncedregioselectivity; and 4 in the ratio 30:70. lM.Yoshifuji,T.Nakamura,andN.Inamoto,TetrahedronLetters,2t'6325(|987),

Tributyltin hydride. hasbeenreviewed(187 . Reviews. The recentuseof this reagentin synthesis but alsoreductive reviewincludesnot only radicaldehalogenation references).rThe

dor cir

TributYltin hYdride

h BuLi lithtum alkane ractlon n(-rlate. ) Thus mainlY h more n shows

313

cleavageofC-O,C-S,C-Se,C-Te,andC-Nbonds'Thereagentislesstoxic and than trimethyl- or triethyltin hydride. The review includessomepreparative work-up recommendations. Curran2hasreviewedrecentapplicationsof the tin hydridemethodfor initiation covers of radicalchain reactionsin organicsynthesis(191references).The review as intrawell as (Giese reaction) intermolecularadditionsof radicalsto alkenes cyclization' radical molecularradicalcyclizations,includinguseof vinyl Radicalcyclization-trapping. Trappingof the initial radicalformed in radical In such reactlons cyclizationscan proceedwith high regio- and stereoselectivity. tin system'3 of a catalytic use by hydrogenatom transferreactionscanbe suppressed Bu'SnCl and (0'1 equiv')' of NaBH,CN(2 equiv.),AIBN fi,r, a systemcomposed than a effective more usually (0.1 equiv.) in (cH.).coH or use of (CoH,).GeHis and sterregiofor used be can stoichiometricprocess.This cyclization-trapping ( + Thus )-prostaglandin eocontrolledformation of two adjacentchiral centers. (1) Fr" (3) has been preparedaby addition of two differentgroupsto a derivative potential a adds step The cyclization-trapping of cis-2-cyclopentene-1,4-diol. -CH,CHO group to one end of the double bond (usedlater in a Wittig reaction) end of the as well as the precursorto the unsaturatedalcoholchain at the other double bond of 2.

OC'H.

o, :

I CH,I

l) cat. Bu'SnCl(hr) 2) CsHrrCOCH(TMS):CH, 3) Pd(oAc):

CrHtt

R3Sio RrSiO'

H. rTMS l)

1:r(cH')3cooH (cH2)4cHl

tit'rn of 3

ir

red (187 reductive

3 The catalyticmethod has also been used to effect (hydro)methylationof the doublebond of an allylic alcoholwith introductionof a methylgroup adjacentand cis to the hydroxyl group (equationI).5

Ilibutyhin

hydride

(r) €t.

KOC(CH!)r DMSO

BulSnH

n%

fi% overall

LT

CH3 Vinyl radical cyclization ofenynes. Two laboratorieshave reported that tin radicalsgeneratedfrom RrSnH with AIBN6 or B(C2H5)3,7 add to the triple bond of an enyneto form vinyltin radicals,which can undergointramolecularcyclization with the double bond to form five- or six-memberedrings substitutedby a vinyltin group. The SnR3group of the final product can be removedby destannylationwith dry SiO, in CHTCL.This enyne cyclizationis successfulbecausethe addition of a

n ^ - r qX

fr

Y:t' CH, E = COOCH:

halo cycli whe

*X

tu'tn#.H(cH3), Hll'

,,.ArH(cHi),

H

">91:9). These

,\r,: l9\- l

?

?

*Jn\

L, ' clln ciulls

Bzl' ,

r)KNls(cH,),r,

I

o

^K\a t *>A*Ao,ii?il;o, iil*i:irilb",, --74-st%

!-/

't' Bzl'

quant

o l

I N3

oH

4

> 91:9) 3 (2S,2R

carboximidesare hydrolyzedby LiOH (2 equiv.) in aqueousTHF to (2S)-azido acids(4) with no detectableracemization.However,hydrolysisof 3 [R = C(CH.).] is besteffectedwith HrO, (4 equiv.)and LiOH (3 equiv.)l Diazo transfer to these substratesis best efiectedby reaction of the sodium enolateof 2 with p-nitrobenzenesulfonyl azide.A typical diazocarboximide is obtained in 85Voyield after a quenchwith a pH 7 phosphatebuffer. r R . E . H a r m o nG, . W e l l m a n a ,n dS . K . G u p t aJ. O r g . , 3 81, l ( 1 9 7 3 ) . I D. A. EvansandT. C. Britton,Am. Soc.,l0!t.68{il 0987). r D. A. Evans, T. C. Britton,andJ. A. Ellman,Tetrahedron Letters,2t,6141 0987).

ernar! fan5ier

2,4,6-Triisopropylbenzenesulfonyl hydrazide. Vinyllithium cyclizations.t The vinyl lithiumsformed from trisylhydrazones (9, 486) can participatein intramolecularcyclizations.This anionic cyclizationis presentlylimited to formation of five-memberedrings. It has the advantageof greaterstereoselectivity than a correspondingradicalcyclization.

328

Trimethyletuminulrlithium

thiophenoxide

ExamPles:

t' ^,.r^r-^ (cH,,"+p;!,,f (n,1 n

a--l

CL;

9H,

hy ?l

oa

X = NNHTris

> 50:1) (cisltrans

fn

cHt1il t l

(fn, ll,Ji,tiii",, l l

6

\,^CH, X = NNHTris

r

CHrBr

Pn

%

CH, = 10:l) (cisltrans

IA.R.Chamberlin,S,H.B|oom,L'A.Cervini,andC.H.Fotsch,.4m.Soc',110,4788 (1e88). Trimethylaluminunelithium thiophenoxide' (10' 163-164)' The oxahydrindene Michael'atdol cyclization oTieto enootes be generatedconvenientlyby reaction skeletonpresentin avermectinantibioticscan with the ate complexof AI(CH')' of the keto enoatel, preparedfrom n-ribose' to the enoate group provides an and LiSC6H5.Conjugate uOOltionof the reagent a l u m i n u m e n o l a t e t h a t u n d e r g o e s a l d o l r e a c t i o n w i t h t h e k e t o n 3' egrouptogive2 providesthe oxahydrindene in 89Voyield.' Sulfoxideelimilnationthen

coocH3

t. ; B

Tn pfl

ch H( s.l ob

Trimetbylgermanium chloride I D. M. Armistead and S. J. Danishefsky, Tetrahedron Leuers,2E,4959 (1987).

CH ( \

!(r l)

Tlimethylamine oxide. Anhydrousrcagent.t The commerciallyavailablematerialis a dihydrate.Anhydrousreagentcan be obtained by distillation of a solution in DMF until the water has been eliminated,followed by slow crystallizationof the resultantconcentratedsolution;m.p. 225-227"dec.,94Voyield. [3 + 2lCycloaddition(13, 326).'The azomethineylide (a) generatedwith LDA from trimethylamineoxide addsstereoselectively to the dihydronaphthalenes I to providethe benzisoindolines 2, of use as c-adrenergicagentsin therapy.

16 rr88

CH3 2 nndene reJction \l((-H,)r yrJcs an o gtre2

'J. A. Soderquist (1986). andC. L. Anderson, Tetrahedron Leuers,27,3961 2B. De,J. F. DeBernardis, andR. Prasad, Syn.Comm.,lt,481(1988). Tiimethylgermrnium chloride. Aldol condensation with germanium enolates. The germanium enolate of propiophenone,preparedby reactionwith LDA in ether followed by metal exchangewith (CHr)rGeCl,reactswith benzaldehyde to give mainly the syn-aldol2. However,if the LiCl formed on transmetallation is removedby centrifugation,the salt-freegermaniumenolategivesmainly the anri-aldol2. This salt effect is not observedwith the germaniumenolatepreparedwith triphenylgermanium chloride.

o il

loocH3 \

I

( ocH3 t

jlialii,;'l3i

o

ri -r-ici ll 4)c6H'cHo ) c.H^ c6H5ccH2cH3 I

oH I

I CH,

o o H l l , cnH. + c^Hi^Y C^H. I CH.

syn-2 + BF3.O(C2H5)2

+ LiBr

88Vo 82Vo

anti-2

30:70 75:25

I Y. Yamamotoand J. Yamada,l.C.S.Chem.Comm.,802(1988)

330

2-TrimethYlsilYloxYfuran

Trimethyl orthoformate. with orthoestersin the Selictiveprotection of 112-or Ir3-diols't Diols react CSA) to form an acid' presenceof an acid cataiyst (such as 1'0-camphorsulfonic to a monoacetal DIBAH by orthoesterthat can be reduced,without isolation,

sii', (r)fy"t +(cH,o)3ccH, lO.X.;,] V"'on

ac tcr

b;-

+*'

60

OH

(equationl).Thissequencecanprovideamethodforpreferentialprotectionofa secondaryover a primary hydroxyl group (equationII)'

v'

pn

l) (c,H5o)rcH

rn clc

(u) HocH'cHot 2g#-HocH'cHocH2oc2Hs CH,

CH,

( 5 :l ) Letters'29' 1947(1988) rM. Takasu,Y. Naruse,and H. Yamamoto,Tetrahedron

/4.

l-\ \Ot

-/

(1) 2-Trimethylsilyloxyfuran, (CH3)3SiOSuppliers:Aldrich, Fluka. Diastereoselectivealdolcondensations.Thisfuran(1)canundergocondensationwith aldehydesasa butenolideto form D-hydroxy-a,p-unsaturated-1-lactones can be controlled by the choice of catalyst' Lewis (2). The diastereoselectivity

n

. .4/Y..* OH

anti-2

!rc

A A

- /'?Y* (D r + RcHo + TESpTf 85-95Vo + BuoNF- 5o-75vo

c.

sYn-2 '15-82:25-18 15-35:85-65

OH

T1 rrc

bu

Trimethylsilylmethanol

rr. rn the I irrlrfl

OO

Ofl t\.rc€tBl

{

331

acids,particularlyBF, etherateor triethylsilyltriflate (TESOTf), favor arri-diastereoselectivity; the useof fluorideion favorss),rr-diastereoselectivity (equationI). These productscan be reducedby sodium borohydridein combinationwith nickef(Il) chlorideto the correspondingE-hydroxy-1-lactones in 90-95% yield.l Butenolides.2 When activatedby silvertrifluoroacetate,this furan is alkylated by primary alkyl iodidesor ethyl o-iodoacetateto give 4-alkyl-2-butenolides (2) in 60-807o yield. RI. AB(l), cHrctl

)H

/

\

;-80'.'o4oAn

(cH3)3sio I

)cHocH3 CH.

r c . W. Jefford,D. Jaggi,and J. Boukouvalas,TetrahedronLeilers,n, 4037(1987). z c .W. Jefford,A. W. Sledeski,and J. Boukouvalas.,/.C.S. Chem.Comm..364(1988).

e a l l ( ) no f a

p-Trimet\ls\lethyl chloroformate, (CH,).SiCHTCHTOCOCI(1). The reagent is preparedby reactionof p-trimethylsilylethanol and phosgene. N-Debenzylationof t-amines.t The reagentconvertsN-benzyltertiaryamines into the correspondingp-(trimethylsilyl)ethoxycarbonyl derivatives,which are cleavedby fluoride ion (8, 470-471)to sec-amines. Example:

c2H5ooc 1l*.H,coH5

\J

8;

c2H5ooc c,H5ooc e.o2cH2cH,si(cH,),+* e* g(r condenl-a-lactones ,lrrt. Lewis

The reactionis not useful for N-demethylationbecauseof slow rate and low yield. In fact, selectiveN-debenzylationis possiblewith this reagent. I A. L. Campbell, D. R. Pilipauskas, I. K. Khanna,andR. A. Rhodes,Tetrahedron Letters, 2t,2331 (1987).

Trimethylsilylmethanol, (CH,),SjCHrOH(f). Suppljers:perrarchSystems,Aidrich. Hydrorymethylation.t Timethylsilylmethanolis converfedby reactionwith butyllithiumand co, and then with sec-butyllithium into the lithiatedlithium

Trimethylsilylmethyl trifl uoromethrnesulfonde

carbonate2,whichconvertsesters,acidchlorides,andnitrilesintohydroxymethyl carbonyl comPounds. sec-BuLi,

1) BuLi, THF

t)to' I

-""

, (CH3)3SiCHOCOrLi I Li

, (CH3)3SiCHrOCOrLi

t

-l-

.",Ocooc2H5

f cH,sicHoco'lil I

I I

fl

l-iP-CH,C6HTCCHzOH 06-/0

a

I

L o''\

J

TI ofG meth from imnx

Letters'8' 1847(1987)' rA. R. KatritzkyandS. Sengupta, Tetrahedron (L)' 11' 578' 2-Trimeihylsilylmethyl'3'acetoxy'1'propene of a Pd(0) catalyst' 1 adds to presence the In Cyclo-addition to aldehydes' It also addsto aldehydes electron-pooralkenesto gine methylenecyclopertanes. is usedasa cocatalyst'' acetate tributyltin when to form methylenetetrahyirofurans Example: C{l,Si(CHti

CHO

+

/

pd(o),

Bu.SnOAc CHz -- "*-

\

f

CH2OAc I

Letters'27' 5971(1986)' lB. M. TrostandS. A. King,Tetrahedron (CH')3SiCH'OTf (11' Trimethylsilylmethyl trifluoromethanesulfonate, Azomethineylides.'Thereactionoflwiththeoximeofanaldehyderesults to an azomethineylide (a) in an iminium salt 2. Desilylationof 2 (CsF) givesrise alkenes(equathat undergoes1,3-dipolai cycloadditionwith electron-deficient tion I).

' A .P Tiir

p

cataly p-lact

Trimethylsilyl

melh\ I

(I)

CuHt

+

"F*ot

r

CuFlr.

CH'Si(CH3)j

-l CsF

orr |Ni 'oH H'

t-CuHs.-?"' I

L

Filr.. toH

H'

OH

cH3o2c\ /.H a+ FC. _CorCH, H,

I

E ;

1N\-cuFIt

\ /

cH3o2c'

cozcH3 3

CH.OH

The salt2 reactswith dimethyracetyrenedicarboxylate (DMAD) in the presence of csF (or NaH) to form an isoxazolidine(4). which is formaily derivedfrom Nmethyl-C-phenylnitrone. This reactionis believedto involveremovalof the proton from the oH group of 2 to give b, which cycloaddswith DMAD to providec, the immediateprecursorto 4.

,-*f _ o_ t'"'FI,

add\ to d e h rd e s a l J l \ s l .'

H'

cH2si(cH3)3 t't'\ cH.o,cc-cco,cHi,

'cHrsilcHr;, 6

*.p

,tr
90vo yield. It alsoeffectscondensation of acidsand amines to form amides.The reactiorrof an aryl carboxylicacid with an o-phenylenediamine promotedby I provides2-arylbenzimidazoles in >gTvo yierd (equationI). If the

and

g:' , anu n ur e loup lateJ ).{l

'\1.

/"'tttNtl'

ll

Z\r-\ * H o o c A r -r.cH:cr:,rs.

\,,\NHR

\-AN'

(l) |

"G;*

|

R = H, CnHs

ll

)-Ar

I

R

by-productof thesereactions,triphenyrphosphine oxide, interfereswith isolation of the product, dehydrationcan be effectedwith a relatedreagentpreparedfrom (C6H5)rPON(CH,CHr),NCHr and triflic anhydride,which furnishesa water-soluble phosphinamidetriflate as the by-product. 'J. B. Hendrickson andM. S. Hussoin, J. Org.,52,4137 (19g7\. 6-(Triphenylphosphoranylidene)-2,4-hexadienoic acid, methyl ester (1). Polyenesynthesis.t The Vedejstrienic phosphorane I 1e,r+-rs) is usefulfor synthesisof bifunctionala,-trans polyenes,since the mixture of (E)- and (z\-

338

Tris(rl-bromophenyl)eminium hexechlorostibnale r 8

isomersformed in the Wittig reaction can be isomerizedby iodine. Reactionsare also cleanerwhen a radical scavengeris present.The reagentis well adaptedto reiterativereactions. Example:

T1i

pre 9H,

t"'7-q oty'.--/-a"o

l) cHrcrr

inal

+ (coH,).P?'\2"'''Z\coocH, 2#l r) DTBAH 2) MnOr

R(C

Ft' CH,-J-o

d-..Ao..-.4."o

T elinu

I S. Hanessian 1151(1987)' Leuers,2E, andM. Botta,Tetrahedron

t I

Tris(4-bromophenyl)aminiumhexachlorostibnate,(p-BrCuH).frSbCl6- (f)' DielyAlder catalysis.t This radical cation can increasethe endo-selectivity of Diels-Alder reactionswhen the dienophileis a styreneor electron-richalkene' This endo-selectivityobtains even in intramolecular Diels-Alder reactions' Thus the triene 2, a mixture of (Z)- and (E)-isomers,cyclizesin the presenceof l to 0" to the hydroindanes3 and 4 in the ratio 97:3. Similar cyclizationof (E)-2 results in 3 and 4 in the ratio 98:2; therefore,the catalystcan effectisomerizationof (Z)is observedwhen the styrenegroup of 2 2to (E)-2. Even higherstereoselectivity (SC6H5 in placeof C6HaOCH3)' group is replacedby a vinyl sulfide

CnHTOCHTP ,CoHaOCHyp

1.0" cH:cl:

invo wirh can I €tal chok or wi

I

R

.C6HaOCH3-p .H

I B

M

) :r .Tr

Tris(dibenzylidenacetone)dipalledium.chtoroform ' B. Harirchian and N. L. Bauld, Tetrahedron Letters,2E,g27

..;gg7\.

Tlis(dibenzylidenacetone)dipalladium.chloroform, pdr(dba),.CHCI. (l). Reductive cleavageof enedicarbonates.t The dicarbonatesof enediolsin the presenceof this Pd(0) complexand triisopropylphosphiteundergo reductiveelimination to afford 1,3-dienes. oco:cHt x(ctlr)/\-''2""-,zocorcH3

pd(r). p(oR), rHF:s' ) R(CH.)a'\-'\CH,

+ O:p(OR)r

(60-79cit I

ocorcH.

; 6

r E

F 2

This elimination fails with diacetatesof enediolsand involvesan overall cis_ eliminationin cyclicsystems. Terminalallenes.2 A synthesisof 1.2-dienes (3) from an aldehydeor a ketone involvesadditionof ethynylmagnesium bromidefollowedby reactionof the adduct with methyl chloroformate.The product. a 3-methoxycarbonyloxy-1-alkyne (2), can be reducedto an allene by transferhydrogenolysis with ammoniumformate catalyzedby a zero-valentpalradiumcomplexof r and a triarkylphosphine.The choiceof solventis also important. Best resultsare obtainedwith rHF at20-30 or with DMF at 70'.

X>.:"

+HC:cMsBr +crcoocu, *#i

i