Asymmetric transformations involving 1,2-diarbonyl compounds as pronucleophiles

14 Pages·2017·1.58 MB·English

Asymmetric transformations involving 1,2-diarbonyl
compounds as pronucleophiles
Wilfried Raimondi, Damien Bonne, Jean Rodriguez
To cite this version:
Wilfried Raimondi, Damien Bonne, Jean Rodriguez. Asymmetric transformations involving 1,2-
diarbonyl compounds as pronucleophiles. Chemical Communications, 2012, 48, pp.6763-6775.
￿10.1039/C2CC30691C￿. ￿hal-00736692￿
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Citethis:Chem.Commun.,2012,48,6763–6775
FEATURE ARTICLE
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Asymmetric transformations involving 1,2-dicarbonyl compounds
as pronucleophiles
Wilfried Raimondi, Damien Bonne* and Jean Rodriguez*
2
1
0
2 Received31stJanuary2012,Accepted24thApril2012
mber 1C DOI: 10.1039/c2cc30691c
pte069
e3
8 SCC Thisarticleconcentratesontheversatilenucleophilicreactivityof1,2-dicarbonylcompounds
22
n C invariousasymmetrictransformations.Althoughunderexploitedincomparisontotheir
e o39/ 1,3-dicarbonylhomologues,thepresenceofadjacentmultiplereactivecentresallowsthe
e0
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e la c.or seven-memberedringsystems.Recentcontributionsinthefieldofbiochemical,organometallic
niversite dp://pubs.rs aastnreedredooisrccghuaesnmsiecidccaaflrtioasmlsyuteiscsy.ntrtahnetsifcoramndatmioencshaasniwsteilclpasoisnotmoefrveielewvsanhtigshtoliigchhtiionmgestormiceapimprpooarctahnest
bliotheque de L'uApril 2012 on htt IPhnaystrruboveidecnuacuctisideo,dnoanseaonfutchleeospimhiplelefsotr1t,h2o-duiscaanrdboyneyalrscobmypNoautnudres1, Racahs1eect,m2he-neodytsilceyral,eerac1bct,oi2tven-edkyealetmcoffioicmadiceepindloitsgulyanwtdwieorianetshss.ah4hdoTy2wdhsrneyonaxtoptyhlpbaoamenrepi(nnFaetrilgtydi.ces1urim)il5vaparrletlyeimvuueasssieenffeooudrfl
nloaded by Biblished on 25 biaatrnrseaeltnafei-nikngeel-tyctohcaorebacbocoiinndojsupywgonalayttshheesy.sad2icsrcoIooxnmfylpspailtaaiesrldhiacelaldea-lkn,bedtytohuealBocesifidrorzsnsetiflcoiuusasyncndiidtnhisne1swvi8seh3ri5tcoe.h3-f utthrnaeUknirnsnfoctoihwlrimnrnaauoltnwhioty,indlsurtahtwizeloaispsnaietomisonobnesyetrloEynfnolid1mne,-2ridts-eidridineccatttorhbuetoshneneiyonlifesntacieir-nsekae(savteoisddyeemesitlmneefcrerstatrr)oai.cs-
wu
DoP philicketonereactivitybythepresenceofanadjacentcarbonyl
Aix-MarseilleUniversite´,UMRCNRS7313iSm2, group.Infact,1,2-dicarbonylcompoundsaresometimesused
CentreSaintJe´roˆme,service531,13397Marseille,France.
allowing the extension of reaction scope that was limited to
E-mail:[email protected],[email protected];
aldehydes.6Nowadays,theelaborationofnewmethodologies
Fax:[phone];Tel:[phone]
WilfriedRaimondiwasbornin Damien Bonne was born in
Orsay(France)inJune1986. Epinal (France) in 1979.
In 2006, he joined the Ecole After studying chemistry at
Nationale Supe´rieure de the Ecole Supe´rieure de
Chimie de Clermont Ferrand Chimie de Lyon (CPE Lyon,
(ENSCCF) where he was France), he completed his
awarded both his MSc and PhD in 2006 under the super-
BSc in chemistry. He is now vision of Prof. Jieping Zhu
pursuing his PhD under the working on isocyanide-based
supervision of Prof. Jean multicomponent reactions. He
Rodriguez and Dr Damien then moved to the University
Bonne at Aix-Marseille of Bristol (UK) to join the
Universite´. His research group of Prof. Varinder A.
focuses on the development of Aggarwal as a post-doctoral
WilfriedRaimondi new organocatalysed metho- DamienBonne associate. Since 2007 he has
dologies and their application been working as an assistant
intotalsynthesis. professorwithProf.JeanRodriguezatAix-MarseilleUniversite´
(France).Hisresearchinterestsincludethedevelopmentofnew
asymmetric organocatalysed methodologies and their applica-
tioninstereoselectivesynthesis.
Thisjournalis c TheRoyalSocietyofChemistry2012 Chem.Commun., 2012,48, 6763–6775 6763
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Biochemical transformations
Inbiosynthesis,pyruvicacidisusedasakeyC2andC3donor
unit. For example, its direct irreversible carboxylation to
oxaloacetic acid (Wood–Werkman reaction)7 by pyruvate
carboxylases is a key step in the essential Krebs citric acid
Fig.1 1,2-Dicarbonyld2synthon. cycle.8 Alternatively, the pyruvate- and phosphenolpyruvate-
dependent aldolases are a specific group of enzymes that
involving 1,2-dicarbonyl compounds as efficient pronucleo- catalysethestereoselectiveadditionofpyruvicacidtovarious
philesisincreasingrapidlyformainlytworeasons: aldehyde acceptors.9 In bacterial systems, sialic acids are
– First, these reactive species became very popular and biosynthesised by the enzyme N-acetylneuraminic acid
2 particularlyattractivesyntheticscaffoldsthankstotheirdense (NeuAc) aldolase (Scheme 2). The enzyme uses a mannose
1
0
2 number of reactive centres coupled with their ambident derivative 1 as a substrate, inserting three carbons from
ber C reactivity that can be exploited in sequential reactions or in pyruvate 2 into the resulting sialic acid structure 3.10 The
m1
pte069 cascadetransformationstoformhetero-orcarbocycles. enzyme is a type I aldolase and forms an enamine with a
SeC3 –Asecondreasoncouldbetheimportantprogressthathas lysine residue and the pyruvate which then reacts with the
8 C
n 2C2 beendoneinthedevelopmentofnewsuitableselectiveactiva- N-acetyl-D-mannosamine in a reversible manner. The imid-
e o39/ tion modes for enhancing the nucleophilic potential of azolegroupofahistidineresidueispresumedtoprotonateand
ne10 1,2-dicarbonyls towards cross-condensation instead of their activatethealdehydegroupoftheacceptorsubstrate.
e la Mediterrac.org | doi:10. ccaoonmnIdndpcetyenhctisilstiacitvfie1eoa,2ntru-.edraiecctaairvrbtiitocylneya,lswsepeloewscsitlerlostspryehxitcloeespdtleieomandoainnllsygtruatosteefutushleaslteysnastchyseectlliifcc- pcspoyemMrcumiavfinaectyrietcyisatalufsloydriteahspveyarriedlugaovabanrltedoeirnNaghesuabvaAioeccdaboatenladeolnoyrslaescsduaebrarbslitdeerdcoaaltueorseueaatncodtufiosiiinttnsssghhwtiiigghthhhe
Bibliotheque de L'universite d5 April 2012 on http://pubs.rs feimeitahpteuorrretasbnaiotn-sd,tohmiocewhtiaotlhm-eeyotrhriacovtrergabanenseofno-ceramxtpaalltoyiiosttnesdsa(tSoscgnheutehcmleeerop1w)h.iitlhesusosimnge raNaatuoencnnaelcUddueucerstpAcndauiaotlincaionsknclaresebcsas,cecftlmdoehaiaronranocelrchasoabiltdiussveeeeeadvalpslieerd.nedidc1eorg2titfiswlyvoappiisrltoteaemhynfsyo,,eta1suod3cNtscaaieeeensnxpu,dbtatAeohrqnctoreuhssaxei.aevdo1orl1edseueTfoptssoolrh,saroleoeesatsr,elemeuacttantbhiiinpcoioeoeopnncsseatuamafeottgrraesraenltroyhetsasocuo,elhtdddrmieoneamalhodlolyinudpgcdocoHayee-ll.
nloaded by blished on 2 cothouentcfiaogcmcuerepaottoifortnhaealdtceaCht3ayldsyeusec(dhScraheseam4c,teitoh3ne)s.1cd4aerIpbneonandcycsleogpnrtooturhspewsrteirtauhcctttshuferreo(Som)f
wu theSifacetoformanewstereogeniccentrewith(S)configu-
oP
D ration and an axial orientation in the final product 5. These
Scheme1 Nucleophilicpotentialof1,2-dicarbonyls.
reactions are presumably under kinetic control. On the other
hand, substrates such as 6 with the opposite configuration at
C3sufferanucleophilicadditionofthepyruvatefromtheRe
face,givingthe(R)configurationinproduct7.Inthesecases,
Jean Rodriguez was born in
Cieza (Spain) in 1958 and in
1959 his family emigrated to
France. After studying chem-
istryatAix-MarseilleUniver-
site´ (France), he completed
hisPhDasaCNRSresearcher
with Prof. Bernard Waegell
and Prof. Pierre Brun in
1987. He completed his
Habilitation in 1992, also at
Marseille, where he is cur-
rently the Professor and
Director of the UMR-CNRS-
JeanRodriguez 7313-iSm2. His research
interests include the develop-
mentofdominoandmulticomponentreactions,andtheirappli-
cation in stereoselective synthesis. In 1998 he was awarded the
ACROS prize in Organic Chemistry, and in 2009 he was
awarded the prize of the Division of Organic Chemistry from
theFrenchChemicalSociety. Scheme2 AldolcondensationmediatedinvivobyNeuAcaldolase.
6764 Chem.Commun., 2012,48, 6763–6775 Thisjournalis c TheRoyalSocietyofChemistry2012
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hugeinterestandmoregeneralbiomimeticmetallo-ororgano-
catalysedapproacheshaveemergedduringthelastdecade.
Metallocatalysed transformations
Thefirstexampleofthedirectuseofa1,2-dicarbonylcompound
asapronucleophileinastereoselectivechemicaltransformation
wasreportedbyJørgensenwhoshowedthatchiralLewisacids
could efficiently catalyse the homo-aldol reaction of ethyl
pyruvate (12).17 They used a chiral copper(II)–bisoxazoline
complex 13 providing diethyl-2-hydroxy-2-methyl-4-oxoglutarate
2
1 (14)inapromising80%yieldand96%ee(Scheme6).Infact,
0
2
ber C thistransformationwasatthetimeofitsdiscoveryverysignifi-
m1 cant since it mimics the pyruvate- and phosphenolpyruvate-
pte069 Scheme3 NeuAc aldolase-catalysed aldol reaction: stereochemical dependentaldolases.9ThechiralLewiscatalystpromotesboth
8 SeCC3 outcome. the formation and the stabilisation of the enol-pyruvate and
22
n C controlsthestereochemistryofthereaction.
e o39/ Short after, the same group proposed a related copper-
e0
Mediterrang | doi:10.1 caTa-hktiaesltyomseeedtshtedoridsaos1tl5oergweyoit-ghiavanensdNseim-ntaopnslyteilo-aasce-clieemscsitnivtooeeaMs-taearmn1nin6ico(hSacrcheiadecmtdieeor7ni)v.oa18-f
e la c.or tives 17 that are precursors of highly functionalised optically
niversite dp://pubs.rs pNu-Hrtoeolluwaecentvoeesnruelsfto1hn8isyblysgeslmeyloeinxctayillviectrrieamdniusncfeotsiromnaanotdfiotnthheisw4-adosrxaowlimbmaoictieketdyw.taos
bliotheque de L'uApril 2012 on htt AaTkdehthdeoeryetaesdnrseoeivdlbiediomleonseplyt1ead9slleiwavceildrtahainrletvyhcaeatraniaroussuymlasmtaNemrry-ebtlthoyrixioScidphMehib/elaaintnsheaniskuuicimlhafonarndreyyacllcooitx-miwoidinoner/eokpsfey2r1bs0,o.2a1x9-.
Bi5
nloaded by blished on 2 tchoentfroorlSmsciahnetcimeoenth4eofnNetewhuelAy(cfRoa)rldmpoerlaodsdesutpecrrteespoaicrseantuitonrndeeoisrfiatnzhateshruemgeaoqrdsu.yantaomriaicl
wu
oP position.
D
Azasugars have been also prepared with NeuAc aldolase
(Scheme 4).15 The biocatalysed addition of pyruvate 2 to
mannosaminederivative8isfollowedbyreductiveamination
to give the pyrrolidines 9, which was further converted into
Scheme6 ChiralLewisacidcatalysedhomo-aldolreaction.
3-(hydroxymethyl)-6-epicastanospermine10.
Otherpyruvate-andphosphoenolpyruvate-dependentaldolases
have been isolated, purified and exploited in synthesis. For
example, 2-keto-3-deoxy-6-phospholuconate (KDPG) aldolase
was shown to efficiently catalyse the aldol reaction between
2-pyridinecarboxaldehyde11andpyruvate2withanextremely
highlevelofenantioselectivity(Scheme5).16
Although of particular relevant importance in Nature the
specificity of the enzymatic systems involved for the selective
functionalisationofpyruvicacidhasencounteredonlylimited
applicationinsyntheticorganicchemistry.However,thehigh
syntheticpotentialofsuchasimplecondensationhasraiseda
Scheme7 Asymmetric direct Mannich reaction of 1,2-keto esters
Scheme5 KDPGaldolase-catalysedenantioselectivealdolreaction. witha-iminoesters.
Thisjournalis c TheRoyalSocietyofChemistry2012 Chem.Commun., 2012,48, 6763–6775 6765
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2
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e la c.or
niversite dp://pubs.rs Sa-ckheetmoea8nilidDeisr.ect syn-selective asymmetric Mannich reaction of
bliotheque de L'uApril 2012 on htt gStscheo-tlaiemelmlc,pptiitrlnvehooexedr2uaue1cmdstepuidriconoetfismolaon2olw2itopeefhdirnatthtyhgiecieoekolsNdeydt-nota-yhnMniieeodlampdnshsoenelaiineecncethydts-iutvosyliffetpoyl2een.2crytHeulivasiiicigmtnthyigiolny(nKeS,scdBahiaffHaeffsom4otreegrdrdaie8nevo)dge-. Sa-ckheetmoea9nilidDeisr.ect anti-selective asymmetric Mannich reaction of
nloaded by Biblished on 25 tsthhteeeOrebno-ceagolyemkneyapilcrl-egcam-efatnemetnrritetnahsoriyw-saii-tmahhnpyatdoin-rrsoteaaxlnneyttciat/rismevypeinodrerdtes,li2arteh3ticeowtsniatschmhaitetpha.trleyeatemiccodneetnsicgarnuibotieuods-
wu
oP selective Mannich-type reaction of a-keto anilide donors 19
D
with N-o-nitrophenyl sulfonyl imine 20b (Scheme 9).20 The
homodinuclear nickel complex 24 promoted the reaction to
affordtheproduct25inupto99%yieldwithananti/synratio
of more than 50:1 and up to 95% ee. The products of the
reactioncould be stereoselectively reduced withK-Selectrides
to give the a-hydroxy b-alkyl g-amino amides 26 with three
stereogenic centres with an anti/anti relative configuration.
These products could also be easily converted to the optically
activeazetidine-2-amides27withasyn/anticonfiguration.
Thefirstexampleofadiastereo-andenantioselectiveconju-
gate addition of 1,2-keto esters to nitroalkenes was reported
by Sodeoka and co-workers in 2010.21,22 They used a mono-
nuclear nickel complex with a chiral 1,2-trans-cyclohexane Scheme10 AsymmetricMichaeladditionof1,2-ketoesterstonitro-
diamineligandandtheanti-Michaeladducts28wereisolated alkeneswithmononuclearNicatalyst.
ingoodtoexcellentyieldandselectivities(Scheme10).Oneof
the main advantages of the method over the previous use of showed that 1,2-keto esters could efficiently participate in an
1,2-dicarbonyl as nucleophiles in metal catalysed stereo- elegant asymmetric Michael–Michael–Henry sequence with
selectivetransformationsistherelativelylowcatalystloading nitroalkenes as electrophiles catalysed by a new copper(II)
required(1mol%).Thesyntheticusefulnessofthismethodo- complex incorporating a rigid chiral diamine (Scheme 11).23
logy was proven by its application to the synthesis of the The counter anion played an important role and the copper
kainic acid analogue 29 in only eight steps from the Michael salt containing the acetate anion proved to be the most
adduct28ainapromising42%overallyield. efficient one for achieving high reactivity and selectivities in
Michael adducts 28 can further react in successive domino theformationofhighlyfunctionalisedcyclohexanes30.Using
reactionasshownveryrecentlybyHuangandco-workerswho triethylamine as an additive (5 mol%), the catalyst loading
6766 Chem.Commun., 2012,48, 6763–6775 Thisjournalis c TheRoyalSocietyofChemistry2012
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2
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niversite dp://pubs.rs Scheme11 Asymmetricsynthesisoffunctionalizedcyclohexanesvia
bliotheque de L'uApril 2012 on htt Mcdaomeiuscichlddraeiebsble–eadMsdiescucthasraiernetalig–sneHgdbemintforuayn0tdec.1rotiimamolinsnoaol(l%vsiedo.qerTugiehanninfcsreoas.ce)a.qtuaelynscieswaansdpr1ev,2io-kuestloy sSbecelheeBcenetmisvseiedu1eac3sc-aemCsCsi–fnhuCairltaliyolbnboaionscofdtxi1va,fa2zoo-tkrelimednteoa–ttoeciosotpfneoprssre,.mr(1II,)C2c-–odNmicpablreobxnocdnatsyallsiynsehdaavesnetaenaretlisooo--
nloaded by Biblished on 25 TansihcySekmhepimlbraoecstodramuikccipt’1ssle,g4x3r-1ao2duw4dpeitretieomonopcbloaottfayaienaldye-skdteheteionapgarceonovoimliioddpueltsseolmy1eed9xnecttveaoelrlleyonnpittesrydyoniade-llsikdneesluenccweltseii.vta2her4 swecenahltaeoancltytiaivsoreesedemlueabncnytdinvoeeaur.bAdtcehindrierleycaatlrplyabio-irsnaeomepxeoiranrsztaobtilniyionnJetøh–ricosgofepfinpes1ele,dr2n(,-IakId)neetdoacclosome-wswptieolterhrxsketr31hs35e,
owPu also good selectivities (Scheme 12). As seen previously, the (Scheme 13).25 Products were formed smoothly but their
D
Michaeladducts31couldeasilybeconvertedtothecorresponding purification (flash chromatography) partially erodes the
tri-substitutedpyrrolidines32withasyn/antirelationship,which enantioselectivity.Inconsequence,reactionproductswerefirst
nicelycomplementsthereportofSodeoka(Scheme10). reduced with L-Selectrides to the hydroxy esters 34 and
cyclised to the N-amino oxazolidinone 35. An important
application of this reaction is the facile access to the corre-
sponding syn-b-amino-a-hydroxy esters 36. Hence reductive
cleavage of both carboxybenzyl groups and the N–N bond
by hydrogen and Raneys-Ni, respectively, and subsequent
protection of the amino group afforded 36 in good yield
withoutracemisationofthestereogeniccentres.
Finally, the first example of catalytic asymmetric mono-
fluorination of a-keto esters was described very recently by
Sodeoka and co-workers using N-fluorobenzenesulfonimide
(NFSI) as the fluoronating agent and a chiral palladium
m-hydroxocomplex37(Scheme14).26Thedesiredb-fluorinated-
a-keto esters 38 were obtained in good yields and excellent
enantioselectivity and the ketone moiety could be reduced
to the corresponding syn b-fluoro-a-hydroxy esters with
moderate diastereoselectivity. Anti b-fluoro-a-hydroxy esters
couldalsobeobtainedusingenzymaticreduction(dr>30:1).
A chiral square-planar bidentate Pd-enolate structure 39 was
invokedto explaintheenantioselection of thereactionwhere
Scheme12 AsymmetricMichaeladditionof1,2-ketoesterstonitro- oneoftheenolatefacesisshieldedbyanequatorialarylgroup
alkeneswithbinuclearNicatalyst. oftheligandandthetert-butylestermoiety.
Thisjournalis c TheRoyalSocietyofChemistry2012 Chem.Commun., 2012,48, 6763–6775 6767
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2 Scheme16 Asymmetrichomo-aldolreactionofethylpyruvate.
1
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Mediterrag | doi:10. SchCelmeaer1ly4, oCragtaanlyotimcaestyamllimcectraitcamlyosniso-oflffuoerrisnavteiornsaotiflea-ktoetoolsestaenrsd.
e la c.or provides complementary activation modes of 1,2-dicarbonyls.
niversite dp://pubs.rs EapnoffidssciibeCnl–etNbstyerbseoiomncdposlnytarconhldainsgsotibnergseeotrhvdeeivdneiarngtuethnreetfofofurntmhceatitomionenatlaoislfacbtaioottanhlsyCsta–.rCe
bliotheque de L'uApril 2012 on htt IeOnstreg2rs0a0nc4oo,uclYadtaabmleyamsspeoedtcoitfircaaannlldysfcaoocrtwmivoaartkteiedorsnusss2ihn7ogwoerdgatnhiactc1a,t2a-lkysettso. Scheme17 Enantioselectivecross-aldolisation–lactonisationsequence.
nloaded by Biblished on 25 ccTaahshytleoamylryamsldtee(ts4r4ci01cr)ibcaversiodasissseto-enandaledmobsilyninergewlaaeaccttteeiiorvxana(tmSioocpfnhleeewmthoietyfhl1aap5ny).pr2our8orvglaTiatnheneeo-(tc1eca2tatr)taaalzayloyntslidect msaeldoqTeruheheiynsgdcedeensoemrb4ae7iltnweowneiaeptnnhrtoiaocaes-seboslexencowztcaiiavmsrebiedcoxraxtozeysonlslid-ecaeldpdaroctoilhdilsirsnaeeeti-4ody6neer–ailarvasnecddtloatnoveirrasgaratitooniouonas-
owPu presumably activates the ethyl pyruvate by formation of the catalyst 48 by Landais and co-workers for the synthesis of
D
corresponding enamine 42 while the tetrazole moiety proto- various isotetronic derivatives 49 (Scheme 17).30 To explain
nates theacceptor enhancing itsreactivity to give the b-aldol the stereochemistry obtained, the authors postulated for a
43in55%yieldand86%ee. rigidchair-liketransitionstatewherethebenzimidazoleringis
Exploiting the well-known ambident reactivity of pyruvates, protonated by the carboxylic acid and the aldehyde is
Dondoni et al. disclosed in 2005 an interesting enantioselective activated through hydrogen-bonding with the N–H bond of
organocatalyticdominoreactioninitiatedbyahomo-aldolreac- thecatalystasshownintransitionstate50.
tion.29 This provided for the first time an efficient access to In2010,wehavedescribedthefirstorganocatalyticenantio-
enantiomericallyenrichedisotetronicacid45fromethylpyruvate anddiastereoselectiveconjugateadditionofa-ketoanilides19
(12) catalysed by (S)-(+)-1-(2-pyrrodinylmethyl)pyrrolidines tonitroalkenesusingthebifunctionalaminothioureacatalyst
(44)incombinationwithTFAasco-catalyst(Scheme16). 51(Scheme18).31Inthisnewapproach,wehavedemonstrated
the crucial role of the amide proton in the formation of the
anti-Michael adducts 53 in high yields and high stereo-
selectivities providing a nice complement to Shibasaki’s
syn-selective organometallic activation.24 The proposed tran-
sitionstateinvolveselectrophilicactivationofthenitroalkene
via a bidentateH-bonding interaction with both thethiourea
and the amide moieties. Concomitant soft-enolisation of the
1,2-ketoamidewiththecatalyst’stertiaryaminewouldresult
inarigidmultipleH-bondedtransitionstatewheretheSiface
of the (Z)-enolate 52 would preferentially react with the Re
faceofthenitroalkene.
The versatile reactivity of these chiral 1,2-dicarbonyls was
illustrated by a pseudo three-component domino Michael–
Scheme15 Organocatalysedasymmetriccross-aldolreaction. Michael–Henryreactionwithsimpleketoamide19(R1=Me)
6768 Chem.Commun., 2012,48, 6763–6775 Thisjournalis c TheRoyalSocietyofChemistry2012
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2
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n1 Scheme18 Enantioselectiveconjugateadditionwitha-ketoanilides.
Mediterrag | doi:10.
e la c.or
niversite dp://pubs.rs Scheme20 Enantioselectiveconjugateadditionwith1,2-ketoesters.
bliotheque de L'uApril 2012 on htt anSdch4e-mfleu1o9ro-Dniitarsotesrteyor-eanned5en4anatffioosreldeicntigvetdhoemihneoxcaysculibssattiitount.ed
nloaded by Biblished on 25 coccaeyfnsctclthoareehdsee1x,ri2ane-nakecoet5tnioo5enawsmbiytoihndtthtehhneaeturiceccrleeeoaxoptppielohorniailtitaecindoad.nndc(oSenlcethrceotmrlooepfhs1iil9xic)s.3ct1ehraeIronagcettnehriicss
wu
oP More recently, the Michael addition was extrapolated to
D
1,2-keto esters 56 giving a-functionalised chiral anti-Michael
adducts 57, which were easily converted to five-membered
heterocycles 58 or carbocycles 59 with additional controlled
stereocentres(Scheme20).32
Pa´pai’s model was invoked to explain the stereochemical
outcome of these reactions involving 1,2-keto esters as pro-
nucleophiles (this explains also the stereochemistry of the
enantioselective conjugate addition with 1,2-keto amides).33
Theprotonatedtertiaryamineofcatalyst51bindstothenitro
function, hence enhancing the electrophilic character of the Scheme21 Transition states for the Michael addition of 1,2-keto
nitroalkene,whereasthethioureamoietybindstothestrongly esterstonitroalkenes.
polarised enolate (Scheme 21). In the resulting conformation-
allyrestrainedenvironment,theSifaceofthethermodynamic realised only lately and the first achievement was reported by
(Z)-enolatepreferentiallyattackstheRefaceofthenitroalkene Rueping et al. in 2008. They judiciously used 2-hydroxy-1,4-
accountingfortheformationoftheanti-(R,R)-Michaeladduct. naphthoquinone 60 in a domino Michael-acetalisation C–O
The formation of the syn-Michael adduct, which would come heterocyclisation sequence with a,b-unsaturated aldehydes 61
fromtheRefaceattackofthe(Z)-enolate,isminor(syn:antio underiminiumactivationwithcatalyst62leadingtosynthetically
1:20).Inthistransitionstate,thebindingofthethioureamoiety valuable 1,4-pyranonaphthoquinones 63 in good yields and
to the enolate is disfavored because of the strong steric inter- excellentenantioselectivities(Scheme22).34Treatmentof63with
actionbetweenthebenzylicesterfunctionandthecatalyst. sodiumborohydridefollowedbyHClgaveb-lapachonederiva-
Besides1,2-ketoacidderivatives,highlyreactive1,2-diketonesare tives64insyntheticallyusefulyields.Alternatively,oxidationof
alsoparticularlyattractivespeciesforthedevelopmentofdomino 63producedthelactones65withoutlossofenantiopurity.
reactions by combining both their nucleophilic and electrophilic ThissequenceMichael-acetalisationwaslaterappliedbyWang
characters in successive transformations. However, this was andco-workerswiththesame2-hydroxy-1,4-naphthoquinone60
Thisjournalis c TheRoyalSocietyofChemistry2012 Chem.Commun., 2012,48, 6763–6775 6769
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bliotheque de L'uApril 2012 on htt dbSocuhmteimnwoeit2rh2eacatT,iboMn-u.Sn-dsiaatruyrlpartoeldinoplyr6u2v-caatteaslys6e6d aMsicthhaeel-ealceecttarloispahtiiolne edgdtrieaorSasiuivltm.pearitteliobavoyresrleye7ala,e0ccccttiyhnivacloelmsorhoaindneduexecaerlaaffienlot-lceo1pi,wehy2niie-eldtdilciddo.tunshuaeebl(sfC7toi1–rt)umOtwaiontainusocnsloehfooopfwthhntiehleebhytyqoduwWrioanarxinndygesl
nloaded by Biblished on 25 usknedleetroHn-bbaosneddinthgiocuatraelays6i7saw(iSthchaemcheir2a3l)1.3,52-Ttrhaense-ndaianmtioinmoeinridcaalnlye ed(aSn,iabcomh-luiesinmnastoeaiiotnu2nd4r–aa)cn.ty3ee6cdlsiTksapehtlyueirostuo,nvnaasnebteqasuesened6na6cntehtiiaococasutetiralneelgcyatsi6eva7desbbdwdyouamasalidc-nheeolvierecaMltlorp1oic,ep2hdh-acifelioels–sr-
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oP thesynthesisofvaluabledihydro-2H-pyranes72inhighyields
D
and excellent enantioselectivities. The catalyst probably acti-
vatesdiketone71andb,g-unsaturateda-ketoester66withits
amineandthioureafunctionalgroupsenhancingreactivitiesof
both substrates in a chiral environment for the enantio-
differentiatingstep.
ThesameconceptinvolvinganenantioselectiveC-Michael-
O-cyclisation strategy was reported by Ding and Zhao with
arylidenemalononitriles 73 as electrophiles leading to chiral
2-amino-3-cyano-pyran derivatives 75.37 In this case, the
moderateenantioselectivitiescanbetheresultofalesseffective
hydrogenbondinginteractionwiththenitrilefunctionsandthe
thioureamoietyofthebifunctionalcatalyst74(Scheme25).
Incomplementtotheseheterocyclisations,71actingsucces-
sivelyasnucleophileandelectrophilewasalsoexploitedinan
elegant asymmetric organocatalytic domino Michael–aldol
carbocyclisation sequence, via enamine–iminium activation
with catalyst 62.38 The optically active polyfunctionalised
bicyclo[3.2.1]octanes 77 obtained in good yields from a,b-
unsaturated aldehydes 76 constitute versatile synthetic plat-
forms upon selective fragmentations.53 Oxidative cleavage of
the 1,2-diol obtained after sodium borohydride reduction of
77affordedthetrisubstitutedcycloheptanones78withconser-
Scheme23 Enantioselective organocatalysed Michael-acetalisation vationoftheopticalpurity(Scheme26).Alternatively,bicycle
dominoreaction. 77 could also be converted to the hemiacetal 79 through
6770 Chem.Commun., 2012,48, 6763–6775 Thisjournalis c TheRoyalSocietyofChemistry2012
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niversite dp://pubs.rs Sthcehesmyneth2e7sisMofecbhicayncilsom[3.i2n.1v]oolcvtianngeismysinteiumms.–enamine activation for
bliotheque de L'uApril 2012 on htt
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nloaded by blished on 2 Scheme26 EnantioselectiveMichael–aldoldominoreaction.
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base-induced retro-aldol ring cleavage reaction but with the
concomitantdestructionofonestereogeniccentre.
Fromamechanisticpointofview,theintermediateiminium
80 evolves through a Michael addition with cyclohexa-1,2-
dione(71)togeneratethetransientenamine81,whichsuffers
an intramolecular aldol-type reaction affording the
bicyclo[3.2.1]octanes77afterhydrolysis(Scheme27).
A similar enantioselective domino Michael–Henry cascade Scheme28 EnantioselectiveMichael–Henrydominoreaction.
involving nitroalkenes 82 as electrophiles under bifunctional
hydrogen-bonding catalysis with 83 was reported inde- good yields and excellent selectivities (Scheme 29).40 The use
pendently shortly after by the same group and Zhao’s team of bifunctional catalyst 86 combining Brønsted acidic and
(Scheme28).39Structurallyidenticalbicyclo[3.2.1]octanecores Lewis basic moieties allows specific activation of substrates
wereobtainedwithlowerdiastereoselectivity,probablydueto andresultsincomplementarypolarisationsatthetwoterminal
a base-catalysed epimerisation at the a-nitro position of carbonatoms.Theslownessofthereactionispossiblydueto
product 84. Interestingly, when a-disubstituted nitroalkenes productinhibitionsince87couldalsobindtothecatalystthe
wereemployed,bicyclicstructureswithtwoadjacentquaternary samewayasthatofthestartinga-ketoenones85.
stereogeniccentres wereobtained.Itis notablethatthepresent Nowadays, the creation of C–C bonds by selective activa-
methodology involving non-covalent hydrogen-bonding activa- tion of 1,2-dicarbonyl pronucleophiles largely leads the way
tionnecessitatesfarlesscatalystloading(1–2mol%)compared andtherearemanyotherinterestingreactivitiestobediscovered.
tothepreviousone(10mol%)thatusesthecovalentenamine– Teradaandco-workersopenedupthisnewdirectionveryrecently
iminiumactivation. by demonstrating that hydrogen-bonding catalysis could also
Recently,simplefunctionalisedacyclica-ketoenones85have specificallyactivate1,2-ketoestersforthecreationofC–Nbonds.
beenemployedinanunprecedentedorganocatalyticasymmetric Theyuseanaxiallychiralguanidinebase89forthea-aminationof
Nazarov cyclisation affording a-hydroxycyclopentenones 87 in 1,2-ketoesters15witht-Bu-diazodicarboxylate(88)(Scheme30).41
Thisjournalis c TheRoyalSocietyofChemistry2012 Chem.Commun., 2012,48, 6763–6775 6771