metal-catalyzed carbenoid reactions with iodonium and sulfonium ylides

Review Commentary

Metal-catalyzed carbenoid reactions with iodonium andsulfonium ylides

Paul MuÈ ller,* Daniel Fernandez, Patrice Nury, Jean-Claude Rossier

DeÂ partement de Chimie Organique, UniversiteÂ de GeneÁ ve, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland

Received 22 July 1997; revised 16 September 1997; accepted 18 September 1997

ABSTRACT: Transition metal-catalyzed decomposition of phenyliodonium and diphenylsulfonium ylides was in-vestigated with regard to application in asymmetric carbenoid reactions. Phenyliodonium ylides react in the presenceof Rh(II) catalysts with the same selectivity in inter- and intramolecular cyclopropanations as the corresponding diazocompounds, and intramolecular CH insertions proceed with identical enantioselectivities. With diphenylsulfoniumethoxycarbonylmethylide the Cu(I)-catalyzed cyclopropanation of olefins affordstrans/cis ratios and asymmetricinductions identical with those of diazo compounds, but with Rh(II) catalysts some small, although significant,selectivity variations occur, which are ascribed to coordination of diphenyl sulfide to one of the coordination sites ofthe catalyst. 1998 John Wiley & Sons, Ltd.

KEYWORDS: metal-catalyzed carbenoid reactions; Iodonium ylides; Sulfonium ylides

INTRODUCTION

The thermal and photochemical decomposition of diazocompounds affords carbenes.1 Diazo compounds are alsodecomposed in the presence of certain transition metalcatalysts based on Cu,2 Rh,3 Ru,4 Pd5 or Co.6 Under thesereaction conditions, metal carbenoids are formed asreactive intermediates, which are capable of transferringthe carbene moiety to appropriate acceptors. Thesemetallocarbenes are not, in general, isolable, but convin-cing evidence for their occurrence in transition metal-catalyzed carbenoid reactions of diazo compounds isavailable.7

If the transition metal carries chiral ligands, thecarbene transfer may become enantioselective. Overrecent years efficient methods for high-yield cyclopro-panations,8 cyclopropenations9 and CH insertions10

proceeding with almost perfect enantioselectivities havebeen developed. Despite this progress, large-scale appli-cations of metal-catalyzed carbene transfer reactions arelimited. Among the known examples are pyrethroidsynthesis (Cu-catalyzed cyclopropanation of 2,5-di-methylhexa-2,4-diene)11, the cyclopropanation of iso-

butylene (synthesis of cilastatin)12 and an Rh(II)-catalyzed intramolecular NH insertion (Merck synthesisof thienamycin).13 One of the reasons for this short list ofapplications is the requirement for diazo compounds ascarbenoid precursors, which are potentially explosive,toxic and/or carcinogenic.14 For this reason we haveinvestigated ways to generate metal-complexed carbenesfrom precursors other than diazo compounds. Thesystems investigated are phenyliodonium and diphenyl-sulfonium ylides. For both precursors the possibility ofmetal-catalyzed carbenoid transfer has been suggested,although not demonstrated, previously in the literature.

CARBENOID REACTIONS WITH PHENYLIODO-NIUM YLIDES

Synthesis and thermal, and photochemical de-composition of phenyliodonium ylides

The chemistry of phenyliodonium ylides has beenpioneered by Neilands.15 The ylides (4) are synthesizedby heating activated methylene compounds (1) with iodo-sylbenzene (2) in chloroform. Other procedures useiodosylbenzene and acetic anhydride16 or diacetoxyiodo-sylbenzene (3) in MeOH in the presence of KOH atÿ5 to0°C.17 This latter method of Schank17 is the method ofchoice. It is, however, limited to ylides such as4 carryingtwo electron-withdrawing substituents, such as carbonyl,

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 321–333 (1998)

*Correspondence to:P. Muller, Departement de Chimie Organique,Universitede Gene`ve, 30 Quai Ernest Ansermet, CH-1211 Geneva,Switzerland.Contract/grant sponsor:Swiss National Science Foundation;contractgrant number:20-45255.95, 20-48156.96.Contract/grant sponsor:Societe Academique de Gene`ve.

1998 John Wiley & Sons, Ltd. CCC 0894–3230/98/050321–13 $17.50

alkoxycarbonyl or sulfonyl. Phenyliodonium ylideshaving only one such substituent are not isolable.Alternatively, phenyliodoniumylides havebeengener-atedvia [Rh2(OAc)4]-catalyzeddecompositionof diazocompoundsat40–45°C in thepresenceof iodobenzene.18

Thus, decompositionof 2-diazocyclohexane-1,3-dione(5a) or its 5,5-dimethylderivative5b affordedtheylides6a and 6b in yields of 37 and 71%, respectively.Aplausibleinterpretationof this reactioninvolvestransferof thecarbenefrom thediazocompoundto theiodineviaa rhodium–carbenoid intermediate.However,the proce-dureis not of interestwithin thecontextof ourobjective,whichconsistsof avoidingtheuseof diazocompoundsinthegenerationof metal-complexedcarbenes.

The photochemicaland Cu-catalyzeddecompositionof phenyliodonium ylides, and the reactions of thecorrespondingdiazocompounds,wereinvestigatedundera variety of reactionconditionsby Hayasiet al.16 Theproducts7–10 resultedfrom theCu-catalyzedreactionoftheylide 6b in EtOH at 25°C. Theoccurrenceof a ring-contractedproduct10 (25%), presumablyderivedfromWolff-type rearrangementof an intermediatecarbene,isnoteworthy.Compound10 is also formed in 39% yieldtogether with other products upon Cu(I)-catalyzeddecompositionof diazodimedonein refluxing ezhanol

(5b). Hayasi et al.16 were the first to invoke a Cu-complexedcarbenein the metal-catalyzedreactionsandfreecarbenesin differentspinstatesin thephotochemicaltransformationsto accountfor the variation of productdistribution with differing reaction conditions in thedecompositionof iodoniumylides.

Nicholaset al.19 reactedseveraldiazocompoundsandphenyliodoniumylidesin thepresenceof triphenylarsineandCu(I) or Cu(II) catalyststo generatearsoniumylides.In addition, the [Cu(acac)2]-catalyzed reaction of theiodoniumylide 11aderivedfrom malonicesteraffordeda sulfonium ylide with thioanisoleand a sulfoxoniumylide with dimethyl sulfoxide. When 11a was decom-posedusing [Cu(acac)2] in cyclohexene(12), cyclopro-panationto 13occurredin 38%yield.Theformalcarbenedimer 14 (41%) wasisolatedin addition.Similarily, the[Cu(acac)2]-catalyzeddecompositionof phenyliodoniumbis(phenylsulfonyl)methylide (15), first described byVarvoglis andco-workers,20 affordedthe cyclopropana-tion product16 with 12 (14%). Photochemicaldecom-position of 15 in acetonitrile–cyclohexene affordedtheadduct16 in 31% yield. Photolysisin benzene,in turn,resulted in a 65% yield of formal insertion into thearomaticCH bond.

Although the mechanismof thesereactionswas not

Scheme 1.

Scheme 2.

1998JohnWiley & Sons,Ltd. JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 321–333(1998)

322 P. MULLER ET AL.

investigatedin detail,furtherstudiesby Moriarty andco-workers21 showedthat the situation was complicated.Several phenyliodonium ylides derived from b-ketoesters and b-keto sulfones such as 17 underwentintramolecularcyclopropanationat 25°C in thepresenceof acatalyticamountof CuClin yieldsrangingfrom 76to90%. The reaction also occurred in the absenceofcatalyst,althoughin lower yield. Theproposedmechan-ism of the uncatalyzedintramolecularcyclopropanationinvolvesanelectrophilicattackonthedoublebondby theiodonium center of 17, followed by intramoleculartrappingof the resultingcationic centerof the zwitter-ionic intermediate18. The sequenceis terminatedbyreductive elimination of PhI from the hypervalentintermediate19 to afford 20. An analogousmechanisminvolving radical intermediateswasalsoenvisaged.Therole of thecatalystwasconsideredto consistin electrontransferto theproposediodoniumcenterof theylide. It is

noteworthythat photochemicalreactionof 17 affordednoneof theexpected20.

A carbenemechanismwas ruled out for the metal-catalyzedreactionontwo grounds.First, iodoniumylidesunderwentanumberof cycloadditionreactionsleadingtofive-memberedheterocyclic rather than cyclopropaneproductswith polarized double bonds,and even withalkenes.22,23 In addition, no cyclopropanesare formedfrom 2,4-dinitro-6-phenyliodonium phenoxidewith al-kenes,alkynesand aromatics.24 Second,no Wolff-typerearrangementproductswereformedin the reactionsofthe iodonium ylides which would be expected ifketocarbeneswere involved asreactiveintermediates.25

However,heterocyclicratherthancyclopropaneproductshavealsobeenreportedin carbenoidreactionsof diazocompoundswith a variety of multiple bondsincludingnitriles, acetylenes,carbodiimides,aldehydesand iso-thiocyanates1a,26 and even with certain olefins.27 In

Scheme 3.

Scheme 4.


METAL-CATALYZED CARBENOID REACTIONS 323

addition,the reactionsof 2-diazoniumphenoxidesshowremarkable similarities to those of the analogousphenyliodonium compounds.28 Furthermore, ketocar-benes,when generatedin the presenceof Cu or Rhcatalysts,do not, in general,undergoWolff rearrange-ment.29

Althoughtheobservationsof Moriarty andco-workersdo not definitely rule out a carbenemechanismfor themetal-catalyzed decomposition of phenyliodoniumylides, they arepertinentwith respectto the prospectofrealizing enantioselectivereactionswith thesereagents.The occurrenceof a non-catalyticcompetitivereactionpathway in the intramolecular cyclopropanation ofolefinscould be detrimentalto the enantioselectivityoftheoverallprocess.In addition,if therole of thecatalystis limited to reversible electron transfer, then thepossibility of realizing enantioselectivereactions isunlikely. It shouldbe noted,on the other hand, that aradical pathwaydoesnot, per se, precludeasymmetricinduction. As recentlydemonstratedin the asymmetricversion of the [CuCl]-catalyzed allylic acetoxylation(Kharaschreaction),asymmetricinductionis compatiblewith a radical pathway,providedthat the reactionpro-ceedsin or nearthecoordinationsphereof themetal.30

We consideredthat phenyliodoniumylides would bean attractive extension of our previously examinedRh(II)-catalyzed asymmetric carbenoid reactions ofdiazo compounds.Rh(II) waspreferredover Cu(I) asacatalystbecauseof our past experiencewith Rh-basedcatalysts,andbecauseRh(II) is not knownto participatein electrontransfer.31 If theRh(II)-catalyzeddecomposi-tions of diazocompoundsandthat of the correspondingphenyliodonium ylides proceed via metal-complexedcarbenes,thentheproductdistributionandtheselectivity

exhibited from thesecarbeneprecursorsmust be iden-tical.

Rh(II)-catalyzed carbenoid reactions of iodoniumylides

Intermolecular cyclopropanation and cyclopropana-tion. Thereactionconditionsfor [Rh2(OAc)4]-catalyzedcyclopropanationof olefins with the ylide 11a wereoptimized with cyclohexene(12). In CH2Cl2 at 20°C,both 11a and the correspondingdiazo compound11baffordedvirtually identical productmixturesconsistingof productsof cyclopropanation(13), insertion(21) andcarbenedimer14 in a ratioof 57:38:5.No intermolecularcyclopropanationoccurreduponheatingtheylide 11a(1equiv.) in cyclohexene(20 equiv.) for 3 h at refluxwithout a catalyst.32 The only productsisolated wereunreactedylide and a trace of 14. Under the samereactionconditionsstyrene(22) wascyclopropanatedtogive 23 in 61% yield. The p-methoxy- and p-nitro-substitutedphenyliodoniumylides 11c and 11d bothaffordeda 55%yield of cyclopropanationproduct23.

Allylbenzene(24), representingmonosubstitutednon-conjugatedolefins,reactedsimilarly to 25. With phenyl-acetylene(26) the correspondingcyclopropene(27) wasisolatedin 37%yield (56%with ethyl diazomalonate33).Althoughthisyield is low, it is remarkablein view of thefact that no cyclopropenecan be isolatedupon Rh(II)-catalyzedcyclopropanationof 26 with ethyl diazoace-tate.34

The relative reactivities(krel) of substitutedstyrenestowards the ylide 11a and diazomalonate11b under[Rh2(OAc)4] catalysisweredeterminedfrom theproduct

Scheme 5.



ratios of competition experiments using equimolaramountsof two olefinsin a tenfoldexcessoverthediazocompoundor theylide, respectively.

Thecorrelationof theselectivityof thecyclopropana-tion of styrenes(22), allylbenzene(24) and phenyl-acetylene(26) with theylide 11avsthatof diazomalonate11b exhibitsa slopeof 1.01(Fig. 1). A slight deviation,probablydueto instability of thecyclopropene,is foundfor the cyclopropanationof phenylacetylene(26), butotherwisethe selectivitiesare identical, which suggeststhat the reactionsof both reagentsmay proceedvia thesameintermediate.

The Hammettplot of the relative reactivitiesof thesubstitutedstyrenesvs �� (Fig. 2) has a slopeÿ0.47,which is in the samerangeas the valuesobtainedforcyclopropanationwith free carbenes(r =ÿ0.62 foraddition of dichlorocarbeneto styreneat 80°C).35 Thisweak selectivity is characteristicof carbeneadditions,andis generallyattributedto anearlytransitionstate.5a,36

For the analogous[Cu(acac)2]-catalyzedreactionthe r-valueisÿ1.12.Althoughthis lattervalueis considerably

Scheme 6.

Figure 1. Plot of log krel for [Rh2(OAc)4]-catalyzed reaction ofole®ns 22 (22a, styrene; 22b, 4-methylstyrene; 22c, 3,4-dimethoxystyrene; 22d, 4-methoxystyrene; 22e, 4-nitro-styrene) and 24, and phenylacetylene (26) with dimethyldiazomalonate (11b) vs log krel with phenyliodonium ylide(11a).

Figure 2. Hammett plot (vs ��) for cyclopropanation of substitutedstyrenes (22a±e) with phenyliodonium ylide (11a) catalyzed by[Rh2(OAc)4] (r =ÿ0.47) or [Cu(acac)2] (r =ÿ1.12).



higher than that observedfor [Rh2(OAc)4], its signifi-canceis questionable.It could be simply indicativeof amorepolartransitionstate,butcouldalsobeindicativeofa mechanisticchange.At present,there are no experi-mentaldatawhich would allow a distinctionto bemadebetweenthesepossiblilities.

No reactiontook placewhendimethyl diazomalonate(11b) wasexposedto Doyleetal.’s [Rh2{(2S)-mepy}4]

37

catalyst28. In contrast,the phenyliodoniumylide 11aand its p-nitro- and the p-methoxyderivatives11c and11d, respectively, decomposedslowly within 3 h toafford the cyclopropane23 in yields rangingfrom 12 to20%. However,no optical induction occurredwith thiscatalyst.

Cycloaddition of cyclic phenyliodonium ylides tofurans. In 1991, Pirrung and co-workers7b,38 reportedRh(II)-catalyzedformal 1,3-dipolar cycloadditionsbe-tweencyclic 2-diazo-1,3-diketones5a and b and furan(31), dihydrofuransand enol ethers.The reactionpro-ceedsvia cyclopropanationof the double bond by thecarbenoid,followed by rearrangement.With the chiral[Rh2{( R)-(ÿ)-bnp}4] catalyst39 (29) theadducts32aandb wereisolatedin 44–50%yield with aneeof ca50%.Inourhands,thediazoketones5a andb preparedaccordingto theprocedureof Moriarty et al.18 reactedasexpectedwith [Rh2(OAc)4], butothercatalystssuchas[Cu(acac)2]and [Rh2{(2S)-mepy}4] were ineffective.The iodoniumylides 6a and b, in turn, afforded 32a and b with[Rh2(OAc)4] in 30 and 37% yield, respectively,but no

reaction occurred with [Rh2{( R)-(ÿ)-bnp}4]. Use ofIkegamiandco-workers’[Rh2{( S)-(ÿ)-ptpa}4]

40 catalyst30 resultedin a yield of 21% andan eeat the limits ofcredibility (6%).

Intramolecular CH insertion. Carbon–hydrogenbondinsertions are characteristic carbene reactions. CHinsertionsare particularly favored when carbenesaregeneratedin thepresenceof Rh(II) catalysts.Thereactionthen proceedswith retentionof configuration41 and, inthe presenceof suitable chiral catalysts, with highenantioselectivity.10 The observationof enantioselectiveCH insertion upon Rh(II)-catalyzeddecompositionofphenyliodonium ylides was therefore considered toprovide conclusive evidence for the intermediacy ofrhodium carbenoids.The choice of compoundsto beinvestigatedwaslimited, however,sincetheylide hadtobe stabilizedby two electron-attractingsubstituentsinorder to be isolable. Unfortunately, this structuralnecessityrules out the use of the rhodium(II) carbox-amidatecatalystswhich leadto thehighestenantioselec-tivities in the insertions.At the sametime, the use ofsecondarymesoalcoholswith which the highestinduc-tion has been achievedis problematic, becausetheiracetodiazoacetatesoftengiverisepreferentiallyto achiralb-lactones.42 Thediazoketoester33aunderwentcycliza-tion upondecompositionwith [Rh2(OAc)4] to afford 34in 95% yield.43 Under comparable conditions, thecorrespondingiodoniumylide 33b affordeda 56%yieldof 34. Similarly, thediazo-acetoacetate35aof 2-phenyl-

Scheme 7.



ethanolaffordedthelactone36 in 41%yield in CH2Cl2 at20°C (85% in refluxing benzene).44 In this case,thepresenceof the phenyl group activates the benzylicpositionandformationof the g-lactonetakespreferenceover that of the b-isomer.The iodonium ylide 35b, inturn, affordedthe g-lactone36 in 28%yield.

The diazoester 37a may react via two differentpathways.Intramolecularcyclopropanationof thedoublebond to 38 may compete with intramolecular CHinsertion into the saturatedside-chainaffording 39.40

The decompositionof 37a with [Rh2(OAc)4] affordeda73:27mixtureof 38 and39 (mixtureof stereoisomers)ina total yield of 64%.Whenthe reactionwascarriedoutusing freshly preparediodonium ylide 37b the productratio was 77:23. However, the ratio changedto 90:10when 37b was stored (ÿ18°C, 8 days) before the

reaction.This changein productcompositionis ascribedto a non-catalyzedspontaneousintramolecularcyclopro-panation of the ylide, entirely consistent with thepropositionof Moriarty etal.18 However,it is noteworthythat no uncatalyzedintermolecularcyclopropanationoruncatalyzedintramolecularCH insertionhasever beenreported.

The intramolecularCH insertionof theketoester40acatalyzedby [Rh2{( S)-(ÿ)-ptpa}4]

40 proceedsto 41 in89%yield with 69%ee[R-configurationat C-3], [deter-minedafterconversionto 3-phenylcyclopentanone(42)].Underthesamereactionconditions,thephenyliodoniumylide 40b afforded41 in 78%yield with 67%ee.

In all casesinvestigatedso far, the productcomposi-tion for the Rh(II)-catalyzeddecompositionof diazocompoundsand that of the correspondingphenyliodo-

Scheme 8.

Scheme 9.



nium ylides is identicalwithin experimentalerror.Sincethe intermediacyof rhodium-complexedcarbenesin thedecompositionof diazo compoundsis firmly estab-lished,5 the samemust hold for the ylides. This is notnecessarilythecasefor theCu-catalyzedreactions,wherea differentmechanismmight apply.45

Despitethe mechanisticanalogybetweendiazocom-poundsandphenyliodoniumylides,thesyntheticapplic-ability of theylide methodologyappearsto belimited. Asmentioned above, the ylides are only isolable whenstabilizedby two electon-attractingsubstituents(alkoxy-carbonyl, carbonyl or sulfonyl). They are often moredifficult to purify than diazo compounds,and theirRh(II)-catalyzeddecompositionrequiresrelatively elec-trophilic catalystssuchasRh(II) carboxylates.Unfortu-nately, the Rh(II) carboxamidateswhich have beenshownto be the mostefficient catalystsfor asymmetric

diazodecompositionarenot sufficiently reactivealsotoinducedecompositionof phenyliodoniumylides.

CARBENOID REACTIONS OF SULFONIUMYLIDES

Background

Sulfonium and sulfoxoniumylides are reagentsfor thecyclopropanationof electron-deficientcarbon–carbondouble bonds or of carbonyl groups.46 The reactionmechanismproceedsstepwise via zwitterionic inter-mediatesanddoesnot involve carbenes.The possibilityof generatingcarbenesfrom sulfoxoniumylideswasfirstrecognizedby CoreyandChaykovsky.47 Photolysisof 43in MeOH afforded 46, the formation of which was

Scheme 10.

Scheme 11.



rationalized by formation of an acylcarbene44 withsubsequentWolff rearrangementto a ketene 45 andcaptureof the latter by thesolvent.

Trost,48 in turn, postulateda metallocarbeneinter-mediatein order to rationalizethe formation of cyclo-propanes48 (90%) and49 (5%) upondecompositionofthe sulfonium ylide 47 with anhydrous[Cu(SO4)] incyclohexene (12). The same products, although indifferentproportionsandaccompaniedby acetophenone,were formed upon photolysisof 47 in cyclohexene.49

Diphenylsulfoniummethylide(51) generatedin situ fromthe sulfonium salt 50 using NaH in THF reactedunder[Cu(acac)2] catalysis with simple olefins to affordcyclopropanes52 in 31–48% yield. Metallocarbeneswere proposedas reactionintermediates.50 The systemwas further improved by Cimetiere and Julia,51 whoemployed copper (II) 3-pentylacetylacetonate([Cu(pentac)2]) insteadof [Cu(acac)2], which resultedin an increasein yields to up to 92%.Decompositionofthe ylide 53 in cyclohexene with [Cu(acac)2] or[Cu(pentac)2] affordedthecyclopropane54 in 70%yieldwith an exo/endo product ratio of 20:1. Ylide 53 isthereforea syntheticsubstitutefor methyl diazoacetate.

The formal Rh(II)-catalyzedintramolecularNH in-

sertion of two sulfoxonium ylides 55a and b to givelactams56a and b was reportedby Baldwin et al.52

Reactiontook placein refluxing1,2-dichloroethanewith[Rh2(O2CCF3)4]. OtherRh(II)-or Cu-basedcatalystsdidnot decomposethe ylides or providedonly decomposi-tion products.52

In contrast to the phenyliodonium ylides, whichrequire two stabilizing substituentsat the carbanioniccenter in order to be isolable, one (or even no) suchsubstituentis sufficient in the caseof sulfonium andsulfoxonium ylides. Accordingly, these speciescouldfind complementary applications in enantioselectivecarbenoid reactions. Although other mechanismsformetal-catalyzedreactionsof suchylides may be possi-ble,53 the intervention of metal carbenoidsis usuallysuggestedor implicitly assumed.

Metal-catalyzed reactions of sulfonium ylides

The metal catalyzedcyclopropanationof olefins wasinvestigatedwith ethyl diazoacetate(EDA, 57a) anddiphenylsulfoniumethoxycarbonylmethylide(57b) withRh andCu catalysts.As in the caseof phenyliodonium

Scheme 12.

Scheme 13.



ylides, the observationof identical dia- and enantios-electivity of the cyclopropanationwas expected toprovide evidence for the same reaction intermediatewhenstartingfrom eitherof thecarbeneprecursors.Theylide 57b was prepared according to a proceduredevelopedby Nozakiet al.54

The ylide was surprisingly stable and remainedunchangedwhen dissolvedin CDCl3 at 20°C for 24h,althoughdecompositionproductsstartedto appearafter4days.No reactionoccurredwith theylide in thepresenceof [Cu(acac)2] or [Rh2(OAc)4] in CH2Cl2 at 20°C or atreflux, but cyclopropanationof olefins took place inrefluxing1,2-dichloroethane(DCE).Slowadditionof theylide to styrene (22) (10 equiv.) in refluxing DCEcontaining[Rh2(OAc4)] (2%) affordedthecyclopropane58 in 44% yield andwith a trans/cis ratio of 1:1. WhenthereactionwasrepeatedunderthesameconditionswithEDA (57a) the trans/cis ratio changed60:40. Experi-mentswith otherRh(II) catalysts,suchas[Rh2{( R)-(ÿ)-bnp}4] (29) or [Rh2{( S)-(ÿ)-ptpa}4] (30) affordedsimilardifferencesin the trans/cis ratiosfor 58aand58b (Table1). Theasymmetricinductionsof thereactionswith theselatter catalystswereinsignificant,however.55 Inductions

consistent with results published under comparableconditions with EDA (57a)56 were realized with[Rh2{(2S-mepy}4] (28), but again, the trans/cis ratiosfor 57a and b were different, changingfrom 52:48 to67:33.Whendiphenylsulfidewasaddedsimultaneouslywith EDA to the cyclopropanationreactionof 22, theratio was58:42,intermediatebetweenthat for EDA andylide. Thissuggeststhatdiphenylsulfideintervenesin thereaction,affecting slightly the trans/cis ratios and theenantioselectivities.A plausible rationalizationof thisobservationconsistsin theoccupationof oneof theaxialcoordinationsitesof thecatalystby thesulfideto form acomplexof type59, wheretheotheraxialsiteis occupiedby thecarbene.

In orderto verify whether57aand57b would exhibitsimilar variationsin thecis/transratiosof cyclopropaneswith Cu catalysts,severalolefinswerecyclopropanatedwith the Cu–semicorrincomplex 61 of Pfaltz and co-workers.8b,57 As before,the cyclopropanationswith theylide 57b were effected in refluxing DCE. However,under thesereactionconditions,the cyclopropanationswith EDA (57a) proceededwithout asymmetricinduc-tion. Whenthe cyclopropanationof styrenewascarried

Table 1. Rh(II)-catalyzed cyclopropanation of styrene (22) with ethyl diazoacetate (57a) and Ph2S=CHCOOEt (57b)a

Catalyst X Yield 58 (%) trans/cis ratio ee(trans) (%) ee(cis) (%)

[Rh2(OAc)4] N2 62 60:40 – –SPh2 44 50:50 – –

[Rh2{ R-(ÿ)-bnp}4] 45 50:50 5 3SPh2 47 60:40 0 2

[Rh2{ S-(ÿ)-ptpa}4] N2 57 47:53 2 2SPh2 35 52:48 0 2

[Rh2{2S)-mepy}4] N2 20 52:48 54 (1S,2S) 38 (1S,2R)SPh2 34 65:35 48 (1S,2S) 34 (1S,2R)

a Conditions:syringe-pumpaddition(15h) of 57aor 57b (1.0equiv.)in DCE(5.0ml) to [Rh2L4] (2 mol%)andstyrene(10equiv.)in refluxingDCE(10ml).

Scheme 14.



out at 60°C with addition of EDA over 16h, the eedecreaseddrasticallywith increasingreactiontime.Someirregularitiesoccurredalsoat50°C.This indicatespartialdecomposition of the catalyst, a phenomenonnotobservedin the cyclopropanationsusing the ylide 57b.In order to avoid all complications,the reactionswithEDA werecarriedoutat roomtemperature(seeTable2).

Althoughthereactionconditionsfor cyclopropanationwith 57a and b are not exactly identical, somegeneralconclusionsmaybedrawnfrom comparisonof thedata.Yields of cyclopropanes62 resultingfrom the reactionwith theylide 57barebelowthoseresultingfrom reactionwith EDA. The trans/cis ratiosof the cyclopropanesareconstantwithin 1–5%. The enantioselectivitieschangeslightly more(2–9%),but thevariationsareconsiderablybelow thoseobservedin the Rh(II)-catalyzedreaction.58

It appears justified, therefore, to invoke the sameintermediatefor thecyclopropanationstartingfrom bothcarbeneprecursorsin thecaseof Cu catalysis.Althoughthe presenceof Ph2S in the Rh(II)-catalyzed ylidedecomposition has some influence on the reactingspecies,it doesnot fundamentallychangeits carbenoidnature.This wasdemonstratedby the intramolecularCHinsertion of cyclohexyl diazoacetate(63a) and thecorrespondingdiphenylsulfoniumylide 63b. The diazocompoundreactedwith [Rh2{2S)-mepy}4] in CH2Cl2 at20°C to afford a 34% yield of cis (97% ee) and trans

(93%ee) lactones64 in a 75:25ratio.8 In refluxingDCEthe yield decreasedto 11% and the isomer ratio was68:32,with ees of 88 and 77%, respectively.The ylide63b, in turn, afforded64 with a yield of 8.5%,a 73:27isomer ratio and ees of 93 and 85%. Although thereactionis, at present,not syntheticallyapplicable,theoccurrenceof insertionproductsfrom a sulfoniumylide,the nearly constant cis/trans ratios and degreesofasymmetricinductionsupportthemechanistichypothesisof a metal-complexedcarbeneintermediate.As in theRh(II)-catalyzedcyclopropanations,we noteagainsmallvariations in the resultswhich should be attributed tocoordinationof thePh2S with thechiral Rh(II) complex.

CONCLUSIONS

This researchwasstartedwith theobjectiveof establish-ing iodonium and sulfonium ylides as substitutesfordiazocompoundsin transitionmetal-catalyzedcarbenoidreactions.The prerequisiteis that the reactionsproceedby the same mechanism,involving metal-complexedcarbenesas intermediates.Our results show that thisrequirement is clearly met in the Rh(II)-catalyzedreactionsof iodonium ylides. In the caseof diphenyl-sulfonium ylides, both Rh(II)- and Cu(II)-catalyzedreactionsalso proceedvia metal-complexedcarbenes,

Table 2. Selectivity for cyclopropanation of ole®ns 60 with ethyl diazoacetate (57a) and Ph2S=CHCOOEt (57b) with Cu±semicorrin Complex 61a

Olefin R1 R2 X Yield of 62 (%) trans/cis ratio ee(trans) (%) ee(cis) (%)

22 Ph H N2 75 75:25 78 5422 Ph H SPh2 31 77:23 71 5960a C5H11 H N2 20 72:28 63 7060a C5H11 H SPh2 20 73:27 72 7460b H2C=CH H N2 50 61:39 70 7760b H2C=CH H SPh2 24 60:40 76 8060c Me2C=CH H N2 50 59:41 ndb nd60c Me2C=CH H SPh2 36 57:43 nd nd60d Ph Me N2 42 70:30 5 4860d Ph Me SPh2 20 65:35 7 50

a Conditions:syringe-pumpaddition (16 h) of EDA (57a) or ylide (57b) (1.0mmol) in DCE (4.0ml) to olefin 60 (10.0mmol) and catalyst61(0.02mmol) in DCE, 20°C for 57a, at reflux for 57b.b nd= Not determined.

Scheme 15.



but there are some complications arising from thepresenceof the diphenyl sulfide. As far as the Cu-catalyzedreactionsof phenyliodoniumylides are con-cerned,thedatacurrentlyavailablearecontradictoryandinsufficientto drawa definiteconclusion.

In orderto beof practicalinterest,theylidesshouldbereadilyaccessiblein high yield, easyto purify andstableuponstorage.In this respect,muchhasto beimprovedtomakethemtruly competitivewith diazocompounds.Thesyntheticpotential of sulfoxonium ylides in carbenoidreactionsis currently underinvestigationin our labora-tory.

Acknowledgments

The authorsare indebtedto the SwissNationalScienceFoundation(ProjectsNo. 20-45255.95and20-48156.96)and to the Societe Academique de Geneve (FondsFrederic Firmenich et Philippe Chuit) for financialsupport.

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metal-catalyzed carbenoid reactions with iodonium and sulfonium ylides

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