中国cydia闪退

RecentadvancesinorganocatalyticasymmetricMichaelreactionsYongZhangandWeiWang*Received22ndAugust2011,Accepted16thSeptember2011DOI:10.
1039/c1cy00334hTheMichaeladditionreactionrepresentsoneofthemostpowerfulmethodsfortheformationofcarbon–carbonbondsinorganicsynthesis.
Thankstotherapiddevelopmentofasymmetricorganocatalysis,signicantprogresshasbeenmadeduringthepastyearsinachievingorganocatalyticasymmetricMichaelreactionswithadiversecombinationofMichaeldonorsandacceptors.
Manynewsubstrateshavebeenaccordinglyappliedinthisreaction,togetherwiththenewapproachesdevelopedforthepurposeoftarget-anddiversity-orientedasymmetricsynthesis.
Thisreviewsurveystheadvancesintarget-anddiversity-orientedasymmetricorganocatalyticMichaelreactionsdevelopedbetween2009andearly2011.
1.
IntroductionThedevelopmentofnewchemicaltransformationsforecientandpracticalsynthesisofcomplexstructureshasemergedasthemainobjectiveinsyntheticorganicchemistry.
Forthispurpose,numerousorganicreactionshavebeenexplored,allowingthe(stereocontrolled)synthesisofadiversityofimportantscaolds.
Amongallthemethodsdeveloped,the(asymmetric)Michaelreactionprovestobeoneofthemostversatiletoolsfortheformationofcarbon–carbonbonds,andhasbeenwidelyusedtogeneratevaluablebuildingblocksinorganicsynthesis.
Ontheotherhand,asymmetricorgano-catalysis1hasemergedasanattractiveresearchareaforthesynthesisofopticallyactivecompoundswithinexpensiveandenvironmentallybenignorganocatalystsundermildreactionconditions.
Duringthepastdecade,anumberofelegantorganocatalystshavebeendevelopedfortheenantiocontrolinalargevarietyofreactions.
Accordingly,theorganocatalyticasymmetricMichaelreactionhasreceivedmuchattention,thepreviousprogressofwhichhasalsobeensubjecttosomeexcellentreviews.
2Incontrasttotheearlyresearchontestingtheconceptofasymmetricorganocatalysiswithsimplereagents,recentinvestigationsonorganocatalyticasymmetricStateKeyLaboratoryofAppliedOrganicChemistry,CollegeofChemistryandChemicalEngineering,LanzhouUniversity,Lanzhou,Gansu730000,P.
R.
China.
E-mail:wang_wei@lzu.
edu.
cn;Fax:+869318915557YongZhangYongZhangwasbornin1985inJiangxi,P.
R.
China.
Here-ceivedhisBScin2007fromGannanNormalUniversity.
Then,hejoinedtheresearchgroupofProfessorWeiWangattheStateKeyLaboratoryofAppliedOrganicChemistry(SKLAOC)inLanzhouUniver-sity.
Currently,heiscompletinghisPhDonthedevelopmentoforganocatalyticasymmetricmethodologiesandtheirapplica-tionsinthetotalsynthesisofnaturalproductsandbiologicallyactivetargets.
WeiWangWeiWangwasbornin1972inXinjiang,P.
R.
China.
Here-ceivedhisPhDinphysicalorganicchemistryfromLanzhouUniversityin1998.
AfterhispostdoctoralresearchatUniver-sityofStuttgart(2000–2001)andatUniversityofSouthernCalifornia(2001–2002),heworkedattheInstituteofChemicalTechnology,Univer-sityofStuttgartuntil2006.
HethenmovedbacktoLanzhouUniversityandwasappointedastheCheungKongProfessorfromtheMinistryofEducationofChina.
CurrentlyheservesastheDeputyDirectoroftheStateKeyLaboratoryofAppliedOrganicChemistry(SKLAOC).
Theresearchofhislaboratoryfocusesonhomo-geneousandheterogeneousorganocatalysis,organicporousmaterials,andsolid-stateNMRspectroscopy.
CatalysisScience&TechnologyDynamicArticleLinkswww.
rsc.
org/catalysisPERSPECTIVEhttp://www.
paper.
edu.
cn中国科技论文在线Michaelreactionhavebeendirectedmoretowardsthetarget-anddiversity-orientedsynthesis,3inwhichmanynewsubstratesandapproacheshavebeenattempted.
Inthisreview,wesummarisetheprogressmadeinorganocatalyticasymmetricMichaelreactionsbetween2009andearly2011,withthefocusonthetarget-anddiversity-orientedsynthesisviaasymmetricorganocatalysis.
Werstsurveythenewsubstratesappliedinthereactions,suchasprotected2-nitro-ethenamines,oxindoles,benzofuran-2(3H)-ones,b-carbonylheteroarylsulfones,oxazolones,nitrophenylacetonitriles,and1-acetylindolin-3-ones.
Thisisthenfollowedbythedescriptionofnewapproachesappliedinthereactions,suchasvinylogousandintramolecularMichaelreactions.
ThediversestrategiesforapplyingtheorganocatalyticasymmetricMichaelreactionsinthesynthesisofnaturalproducts(ortheircorestructures)areemphasised.
OtherdevelopmentsrelatedtotheasymmetricorganocatalyticMichaelreactions,suchasorganocatalyticcascadereactionandhetero-Michaeladditionarealsobrieymentioned.
2.
Newsubstrates2.
1Protected2-nitro-ethenaminesThe1,2-diaminostructuralmotifsaswellasthesubstituted3-aminopyrrolidinesareencounteredinalargevarietyofpharmaceuticalmolecules.
Recently,Maandco-workers4developedanorganocatalyticMichaeladditionofprotected2-nitro-ethenamine1toaldehydes2asanecientwaytoprovidethesyntheticallyuseful1,2-diaminoprecursors3(Scheme1).
Inthepresenceofdiarylprolinolsilylethercatalysts4,theMichaeladducts3wereobtainedinexcellentyieldsandenantioselectivities.
Interestingly,thediastereoselectivityof3iscontrolledbytheZ-orE-formofthefunctionalisednitroolens.
Thephthaloyl-protected2-nitroethenamine1withE-formgivesthesynadducts3asthemajorproducts,whileacyl-protected2-nitroethenamine8awithZ-formaordstheantiadducts.
Theopticallyactiveadducts3couldbefurtherderivatisedintothecorrespondingaminopyrrolidines6byaZn/HOAc-mediatedreductive/aminationprocess.
Moreover,viaasimilarstrategydevelopedbyHayashiandco-workers,5amoreecientandpracticalprocedure4wasprovidedfortheenantioselectivesynthesisof()-oseltamivir13from7and8a(Scheme1).
Mostrecently,Yuanandco-workers6successfullyappliedtheprotected2-amino-1-nitroethenes8intheasymmetricMichaeladditionwith3-substitutedoxindoles14fortheconstructionof3,30-disubstitutedoxindoles15bearinga,b-diaminofunctionality.
Theamino-indanolderivative16wasfoundastheoptimalcatalysttoaordthereactionproducts15inveryhighyieldswithexcellentdiastereoselectivitiesandgoodenantioselectivities(Scheme2).
Otherbifunctionalcatalysts,whichprovedtobeecientfornormalnitroalkenes,showed,however,poorenantiocontrolinthisreactionduetothestrongintra-molecularhydrogenbondinginacyl-protected2-nitroethenamine.
2.
2OxindolesOxindolesbearingatetrasubstitutedcarbonstereocentreattheC3positionareprivilegedstructuralmotifsfoundinmanypharmaceuticalsandalkaloidnaturalproducts.
TheasymmetricMichaeladditionofoxindolestoelectron-decientolenshasbeendemonstratedasanecientmethodfortheconstructionofthesestructuralmotifsandcanbefurtherusedinthesynthesisofspiraloxindolesorindolinederivatives.
7Therstasymmetricconjugateadditionofunprotected3-alkyloxindoles14toa,b-unsaturatedaldehydes17awasreportedbyMelchiorreandco-workers.
8Inthepresenceofanewbifunctionalchiralprimaryaminethioureacatalyst19,theadducts18withadjacentquaternaryandtertiarystereo-centreswereobtainedingoodyieldswithhighdiastereoselectivitiesandenantioselectivities(Scheme3).
Later,Maruokaandco-workers9developedachiralquaternaryphosphoniumsalt22asanecientphase-transfercatalystforthisreaction.
AvarietyofN-Boc-3-aryloxindoles14couldbesuccessfullyreactedwithenones20(oracrolein),givingrisetotheadducts21withexcellentyieldsandenantioselectivities.
TheopticallyactiveMichaeladducts21acanbereadilyderivatisedintovaluablenaturalproductsandtheiranaloguesasshowninScheme4.
Scheme1Scheme2In2010,LuoandChengetal.
10realisedtheMichaeladditionofN-Boc-oxindoles14toactivatedterminalalkenes25withabifunctionaltertiary-aminethioureacatalyst27(Scheme5).
Bothvinylketonesandvinylsulfonesareapplicable,givingthechiraloxindolecompounds26withmoderatetohighyieldsanduptohighenantioselectivities.
Theasymmetricconjugateadditionofnitroalkenesisanimportantsyntheticprocessduetothewidepossibilitiesforsubsequenttransformationsofthenitrogroup.
In2009,BarbasIIIandco-workers11foundthatcatalyst30couldecientlypromotetheadditionofN-Boc-3-alkyloxindoles14tonitroolens28.
Thedesiredproducts29withaquaternarystereocentreattheC3positionwereproducedingoodyields,togetherwithgoodtoexcellentdiastereoselectivitiesandenantioselectivities.
Thesyntheticutilityofthisreactionwasshownbyderivatisingtheproduct29afortheformalsynthesisof(+)-physostigmine32(Scheme6).
EnantioselectiveconjugateadditionofN-Boc-3-aryloxin-doles14withnitroolens28wasrealisedlaterbyMaruokaandco-workers.
12Inthepresenceofchiralphase-transfercatalyst33,thereactionproceededwellinwater-richsolvents,aordingthedesiredproducts29inexcellentyields,togetherwithuptoexcellentdiastereoselectivitiesandhightoexcellentenantioselectivities(Scheme7).
Incontrasttothegeneralconditionsforphase-transfercatalysis,thisreactiondoesnotneedadditionalbase.
Theenantioenrichedadduct29bcouldbereducedtothecorrespondingamine,followedbydeprotectionandcyclisationtogiveproduct34,whichhasacorestructuresimilartothenaturalproducts(Scheme7).
Scheme3Scheme4Scheme5Scheme6Scheme7In2010,LuoandChengetal.
13presentedtheMichaeladditionofN-phenyl-3-methyloxindoles35tonitroolens28withasimplebifunctionalalkyl-thioureaorganocatalyst37.
Thedesiredproducts36wereobtainedinexcellentyieldswithmoderatediastereoselectivitiesandgoodenantioselectivities(Scheme8).
Chirala-succinimidesaresyntheticallyandbiologicallyimportantmotifsinasymmetricsynthesis.
TheasymmetricMichaeladditionofoxindolestomaleimidesprovidesapracticalrouteforthepreparationofchirala-succinimides.
In2010,Yuanandco-workers14reportedtheenantioselectiveMichaeladditionofN-Boc-3-substitutedoxindole14tomaleimides38utilisingabifunctionalthiourea-tertiaryaminecatalyst30c(Scheme9).
AvarietyofoxindolesandN-protectedmaleimides(aswellasmaleicanhydride)couldbeusedtoprovidethemultifunctionalproducts39inhighyieldsandwithhightoexcellentdiastereo-andenantioselectivities.
Theenantioselectiveconstructionof1,3-nonadjacentstereo-centresremainsasyntheticchallengeinasymmetriccatalysis.
Theuseofa-branchedMichaelacceptors(suchas2-chloro-acrylonitrile)isaconceivablestrategytowardthisissue.
In2010,LuoandChengetal.
15developedahighlyenantio-selectiveMichaeladditionofN-Boc-3-substitutedoxindoles14to2-chloroacrylonitrile40usingabifunctionaltertiary-aminethioureacatalyst37.
Both3-aryland3-alkyloxindolescouldbeapplied,providingthedesiredproducts41inhighyieldsandhightoexcellentdiastereo-andenantioselectivities.
Theutilityofthismethodologywasexempliedbythesynthesisofpyrroloindolederivatives44(Scheme10).
2.
3Benzofuran-2(3H)-onesBenzofuranoneswithanall-carbonquaternarycentreattheC3positionwidelyexistinanumberofbioactivecompounds.
Therstapplicationof3-substitutedbenzofuranonesinanorganocatalyticasymmetricMichaeladditionwasrecentlyreportedbyLuoandCheng.
16Inthepresenceofalkyl-sub-stitutedbifunctionalthioureacatalyst37,theadditionof3-arylbenzofuran-2(3H)-ones45tochalcones46proceededsmoothlytoaordthedesiredproducts47withhighyieldsandexcellentenantioselectivities,butwithpoordiastereo-selectivities(Scheme11).
In2010,LuoandChengetal.
17extendedtheirmethodologytoincludemaleimides38asthesubstrates.
UtilisingTakemoto'scatalyst30a,theMichaeladditionof38withabroadscopeofsubstrates45aordsthecorrespondingadducts48inexcellentyieldswithhightoexcellentdiastereoselectivitiesandenantio-selectivities(Scheme12).
2.
4b-CarbonylheteroarylsulfonesInmostcases,theMichaelreactionsareapplicableonlyforthebondformationbetweentwosp3–hybridisedcarbonatoms.
Theasymmetricbondformationbetweensp–sp3orsp2–sp3centresremainsachallengingtask.
Recentdevelopmentshavedemonstratedthattheuseofb-carbonylheteroarylsulfonesasnecliphilescouldeasilytacklethissyntheticchallenge.
18Jrgensenandco-workers19reporttherstapplicationofb-carbonylheteroarylsulfones49aintheMichaelreactionwitha,b-unsaturatedaldehydes17b.
Thereactionwascata-lysedbydiarylprolinolsilylether5c,aordingtheprivilegedScheme8Scheme9Scheme10Scheme11additionintermediates50withhighyieldsandexcellentenantioselectivities.
Theintermediates50couldthenbetrans-formedintohighlyvaluablealkynes51andalkenes52viatheSmilesrearrangementreaction.
Thisalsorepresentstherstexamplefortheasymmetricformationofb-alkyne-substitutedaldehydes(Scheme13).
Furtherextensionofthisstrategytotheasymmetricfunc-tionalisationofcyclica,b-unsaturatedketones53waslaterachievedbythesamegroup.
20Inthepresenceof9-epi-aminocinchonaalkaloidsalt55asthecatalyst,thereactionproceededwelltoaordthekeyintermediates54,whichareusefulprecursorsforaseriesofimportantbuildingblocks.
WhenR1arearylsubstituents,alkynes56andalkenes57wereobtainedinmoderatetohighyieldswithmoderatetoexcellentenantioselectivities.
Anorganomediateddesulfonylationfurtherledto1,5-diketoproducts58inmoderateyieldswithexcellentenantioselectivities.
Interestingly,whenR1arealkylsubstituents,21bicyclicproducts59wereobtainedviathesequentialpathwayofintramolecularaldolreaction,Smilesrearrangement,andelimination(Scheme14).
2.
5OxazolonesTheasymmetricsynthesisofnon-naturalaminoacidsandtheirderivativesisanareaofgreatimportance.
Oxazoloneshaveproventobeexcellentreagentsforthesynthesisofa,a-disubstituted(quaternary)a-aminoacids.
22In2008,Jrgensenandco-workers23reported(followedbyHayashietal.
24)therstnucleophilicadditionofoxazolones60witha,b-unsaturatedaldehydes17catalysedbydiaryl-prolinolsilylether5c.
Despiteusingoxazolones60withdierentnucleophilicsites,onlyC4-additionproducts61wereobserved.
Havingbeenobtainedwithgooddiastereoselectivitiesandexcellentenantioselectivities,theMichaeladducts61couldthenbederivatisedtoformdierentaminoacidderivatives(Scheme15).
Soonafterthis,theMichaeladditionofoxazolones60tonitrostyrenes28wasreportedbythesamegroup(Scheme16).
25Withabroadrangeofnitrostyrenesandoxazolonesasthesubstrates,thereactionwascatalysedbycinchonaalkaloidthioureacatalyst67withgoodyields,excellentdiastereoselectivities,andmoderatetogoodenantio-selectivities.
Thesubstituentsontheoxazoloneringwereshowntohaveagreatimpactontheregioselectivity.
AsillustratedinScheme16,thearylsubstituentsintheC2-positionofoxazoloneleadtotheregioselectivityonC2whilealiphaticsubstituents(i.
e.
tert-butyl)giveonlytheC4-substi-tutedadducts.
In2009,Ooiandco-workers26developedasupramolecularcatalyst70fortheconjugateadditionofoxazolone60atoa,b-unsaturatedacylbenzotriazoles68(Scheme17).
TheC2additionproductswereobtainedwithexcellentyieldsandenantioselectivities.
Toshowthesyntheticutilityofthisprotocol,opticallyactivemethylsuccinicacid72wassynthesisedinfourstepsfrom69withoutlossoftheenantiomericexcess.
Enantioselectivenucleophilicadditionofsimpleconjugatedestersoramidesremainsachallengingtaskinorganocatalysisduetothelowreactivitiesofsubstrates.
In2010,Jrgensenandco-workers27demonstratedthattheuseofacylphosphonates73assurrogatescaneectivelysolvethisproblemthroughadoublenucleophilicreaction.
Byemployingabifunctionalthiourea67ascatalyst,theconjugateadditionofa,b-unsatu-ratedacylphosphonates73withoxazolones60proceededwelltoaordtheN,O-aminalproducts74inmoderatetohighyieldsandexcellentenantioselectivities(Scheme18).
Othernucleophilessuchasindolesand1,3-dicarbonylcompoundsarealsotolerableinthisreaction.
ByusingTakemotothioureacatalyst30a,Riosetal.
reportedtheMichaeladditionofoxazolones60to1,1-bis(phenyl-sulfonyl)ethylene7528andtomaleimides38,29respectively.
Thesetwotypesofelectrophilesshoweddistinctregioselectivitiestowardtheconjugateadditionwithoxazolones.
Inthecaseof75,theMichaeladditiontookplaceexclusivelyattheC4position,givingtheprecursorsofquaternaryaminoacidswithhighyieldsandenantioselectivities.
However,whenmaleimides38wereusedaselectrophiles,theregioselectivitywasreversedScheme12Scheme13togiveonlyC2adducts77withexcellentyields,diastereo-andenantioselectivities(Scheme19).
2.
6NitrophenylacetonitrilesIn2010,CidandRuano30foundthatarylacetonitrilesbearinganelectron-withdrawinggroup(suchasanitrogroup)attheortho-orpara-positioncouldserveassuitablenucleophilesinorgano-catalyticprocesses.
Inthepresenceofprolinolethers5c,theenantioselectiveMichaeladditionofp-nitrophenylacetionitrile78tob-alkylunsaturatedaldehydes17couldproceedinahighlyenantioselectivemanner(Scheme20).
ThereactionwasperformedinasequentialprocedureasMichaeladdition/NaBH4Scheme14Scheme15Scheme16Scheme17reduction/lactonisation,allowingthesynthesisofdiastereomericallypurelactones79inveryhighyieldsandenantioselectivities.
2.
71-Acetylindolin-3-onesIndolemotifsarewidelydistributedinnature(especiallyinbioactivenaturalproducts)andpharmaceuticalcompounds.
Duetotheinherentelectroncharacteristicsofindole,theselectivefunctionalisationofindoleattheC2positionhasmetwithlimitedsuccess.
31Veryrecently,Xuandco-workers32addressedanewmethodologyforthissyntheticchallenge.
TheasymmetricMichaeladditionof1-acetylindolin-3-ones80tonitrostyrenes28wascatalysedbyabifunctionalthiourea-tertiaryaminecatalyst67b,aordingthedesiredproducts81withexcellentyieldsandhighdiastereo-andenantioselectivities.
Theseopticallyactiveproductscouldbereducedtothecorrespondingalcohols,followedbyeliminationtogivethe2-functionalisedindoles82withoutlossofenantioselectivities(Scheme21).
Soonafterthis,Wangetal.
33reportedahighlyenantio-selectiveMichaeladditionof1-acetylindolin-3-one80toenones83byusingaprimary-secondaryamine85ascatalyst(Scheme22).
Avarietyofenonescouldbeapplied,givingthecorrespondingadducts84ingoodyields,moderatetoexcellentdiastereoselectivities,andexcellentenantioselectivities.
3.
VinylogousMichaelreactionInspiteofthesubstantialprogressmadeinasymmetricMichaelreactions,mostofthecatalyticmethodologiesareapplicableonlyforthefunctionalisationofelectron-decientolensatthebposition.
TheenantioselectiveconstructionofC–Cbondsatthegpositionofolenshasmetwithlimitedsuccess.
Recently,withtheexploitationofthevinylogyconcept,34theasymmetricvinylogousMichaelreactionhasemergedasaneectivestrategytoaddressthissyntheticissue.
353.
1a,b-Unsaturatedc-butenolidesg-Butenolidesandtheirderivativesarecommonmotifsfoundinnaturalproductsandbiologicallyactivemolecules.
In2003,MacMillanandco-workers36realisedtheenantioselectiveg-functionalisationofbutenolidesthroughanorganocatalysedMukaiyama-Michaeladditionofsilyloxyfurantoenals.
Thisreactionissyntheticallyusefulforconstructingtheenantioen-richedg-butenolidesarchitecture.
However,theuseofsilyloxy-furanisunfavourablefromthestandpointofatomeconomy.
Thus,developmentofthedirectvinylogousadditionsofg-butenolides(aspronucleophiles)hasreceivedmuchattention.
Liandco-workers37disclosedtherstenantioselectiveorganocatalyticdirectvinylogousMichaeladditionofg-bute-nolides86tochalcones47.
Thereactionwascatalysedbythevicinalprimary-diaminesalt88,givingrisetohighlyvaluablechiralg-butenolides87withgoodyields,highdiastereo-andenantioselectivities.
However,thesubstratescopewaslimitedtothesubstitutedg-butenolidesandchalcones.
Fortheunsubstitutedg-butenolide,theenantioselectivityislowandnodiastereo-selectivitycouldbeobtained.
Theuseofsimple2(5H)-furanone86ainthesamereactioninthepresenceofTakemotothioureaScheme18Scheme19Scheme20Scheme21Scheme22catalystwasalmostsimultaneouslyreportedbyWangandco-workers38(Scheme23).
FurtherdevelopmentwithmuchimprovedsubstratescopeandeciencywaslaterreportedbyYeandco-workers39byusinganewcatalyst91(Scheme24).
Avarietyofenones83includingbenzalacetone,chalcones,andalkylsubstitutedenonesareapplicable,aordingthesyntheticallyversatileg-substitutedbutenolides90withsatisfactoryyields,diastereo-andenantioselectivities.
Utilisingtheaminal-pyrrolidinecatalyst94,Angelicalactones92weresuccessfullyappliedinthedirectvinylogousMichaeladditionwithenalsbyAlexakisandco-workers.
40Variousaldehydes17couldbeused,aordingtheg-tetrasub-stituedbutenolides93withexcellentstereoselectivities.
How-ever,2(5H)-furanoneandg-substitutedbutenolideprovedtobeunsuitableforthisreaction,becausetheenolequilibriumofAngelicalactoneoccursindependentlyintheabsenceofthecatalyst(Scheme25).
AlthoughthedirectvinylogousMichaeladditionof2(5H)-furanonetonitroalkeneswasreportedin2009byTrostusingachiralmetalcomplex,41theuseoforganocatalystsforthisreactionwasnotrealiseduntilrecently.
42Inthiscontext,a-tert-butylthio-substitutedfuranones86bwereutilisedasthevinylogouspronucleophiles.
TheMichaelreactionwithnitroalkenes28wascatalysedbyaxiallychiralguanidine96,leadingtodenselyfunctionalisedg-butenolides95inhighsyn-diastereo-andenantioselectivities.
Toshowthesyntheticutilityofthisreaction,thea,g-functionalisedg-butenolideproduct95awasthenderivatisedintob,g-disubstitutedbutenolide98viastandardchemicaltransformations(Scheme26).
3.
2a,b-Unsaturatedc-butyrolactams5-Substituted3-pyrrolidin-2-onesmotifsareprivilegedhetero-cyclicstructures,whichwidelyexistinsyntheticbioactivemoleculesandnaturalproducts.
Recently,a,b-unsaturatedg-butyrolactams99haveemergedasoneofthemostecientprecursorsforthesynthesisof5-substituted3-pyrrolidin-2-onederivatives.
Shibasakiandco-workers43reportedtherstasym-metricMannichandMichaelreactionofa,b-unsaturatedg-butyrolactamscatalysedbyachiralmetalcomplex.
Thereafter,threepublicationsofasymmetricMichaelreactionofa,b-unsa-turatedg-butyrolactamsinvolvingorganocatalysisappeared.
In2010,Chenandco-workers44presentedanorganocata-lyticasymmetricconjugateadditionofa,b-unsaturatedalde-hydes17viaiminiumcatalysis.
Catalysedbydiarylprolinolsilylether5a,thereactionproceededwellwiththeadditionofo-uorobenzoicacid(OFBA),aordingthehighlyvaluedadducts100inexcellentenantioselectivitiesandwithuptooutstandingdiastereoselectivities.
Toshowthesyntheticuti-lity,anumberofnatural-product-likeordrug-likemoleculeswithversatileskeletonshavebeenecientlyconstructedfromtheMichaeladducts100(Scheme27).
Therstorganocatalyticconjugateadditiontoenoneswasreportedin2011byourgroup,45utilisingthecinchonaScheme23Scheme24Scheme25Scheme26alkaloid-basedthioureacatalyst67a(Scheme28).
Variouschalcones47couldbeapplied,aordingthesyntheticallyversatileg-substitutedbutyrolactams107withexcellentdiastereo-andenantioselectivities.
However,thesubstratescopewaslimitedtochalconesonly.
WhenRwasanaliphaticmoiety(e.
g.
CH3ort-Bu),noreactioncouldbeobserved.
Almostsimultaneously,thegroupofYerealisedtheasymmetricadditiontobenzalacetoneoralkylsubstitutedenones83usingamultifunctionalprimaryaminesalt91.
46ThecorrespondingMichaeladducts108couldbeobtainedinhighyields,togetherwithexcellentdiastereo-andenantioselectivities.
Theseadductswerederivatisedintocertainimportantfragmentsunderstandardchemicaltransformations(Scheme29).
3.
35-StyrylisoxazolesAdamoetal.
47havepreviouslydevelopedstyrylisoxazolesasnewvingylogouselectrophilesintheMichaeladditionwithavarietyofsoftnucleophiles.
In2009,Bernardi,Adamoandco-workersfullledthesuccessfulapplicationofstyrylisoxa-zoles111intheasymmetricvinylogousconjugateadditionwithnitroalkanes.
48Usingphase-transfercatalyst114,thecorrespondingadducts113wereformedinmoderatetohighyieldsandwithgoodtoexcellentenantiomericexcesses.
Theseenantiomericallyenrichedadductswerethentransformedtog-nitroesters115andg-aminoacids117withoutanylossofenantiomericexcess(Scheme30).
3.
4b-SubstitutedcyclohexenonederivativesInspiredwiththedienaminecatalysis49developedbyJrgensenandco-workers,Melchiorreetal.
50discoveredthatthechiralprimaryaminesalts120couldselectivelyactivatetheg-positionofunmodiedcyclica,b-unsaturatedketones118throughdienaminecatalysis.
ThedirectvinylogousMichaeladditionofb-substitutedcyclohexenones118tonitroalkenes28proceededsmoothly,aordingtheg-site-selectiveadducts119withhighScheme27Scheme28Scheme29Scheme30yieldsandexcellentenantioselectivities.
However,thesubstratescopewaslimitedtoarylphaticnitroalkenes.
Aliphaticnitro-alkenesdidnotreactundertheoptimalconditions.
Theve-memberedringnucleophiliccomponent(i.
e.
3-methy2-cyclopenten-1-one)wasinactive,whichsuggestedthatthegeometryofthecyclicscaoldstronglyinuencedtheselectiveformationofthedienamineintermediate.
Otherb,b-disubsti-tutednitrostyrene121anda,a-disubstitutednitrostyrene122couldalsobeapplied,leadingtothecompounds123and124withanall-carbonquaternarystereogeniccentre,respectively(Scheme31).
4.
IntramolecularMichaelreactionTheenantioselectiveintramolecularMichaelreactionprovidesanimportantmethodfortheconstructionofchiral,cycliccarbonskeletons,whicharecommonmotifsinnaturalproducts.
Earlyin2004,ListandFonseca51presentedtherstorgano-catalyticasymmetricintramolecularMichaelreactionofaldehydesforthesynthesisofchiraltrans-disubstitutedcyclopentanesandpyrrolidinederivatives.
Despiteofthesyntheticutilityofthismethodinorganicsynthesis,littleprogresshasbeenmadeinthisarea.
52Recently,Cobbandco-workers53successfullyusedthismethodologyforthesynthesisofcyclicg-aminoacids.
ThecatalyticasymmetricintramolecularMichaeladditionofnitro-natestoconjugatedesterswasrstlyrealisedbyusingabifunctionaltertiary-aminethioureacatalyst67.
AvarietyofsubstratesexceptZ-esterscouldbeapplied,aordingthedisubstitutedcyclohexanederivatives126inpoortohighyields,withuptoexcellentdiastereoselectivitiesandenantio-selectivities.
Notably,uptothreecontiguousstereocentrescanbeconstructedinonestepwiththisstrategy.
Toillustratethesyntheticutilityoftheseproductsinthesynthesisofpeptides,N-andC-terminalderivatisationswereperformed(Scheme32).
In2009,Christmannetal.
54disclosedaRanhut-CurriertypeintramolecularMichaelreactionviadienamineactivationfortheconstructionofaniridoidframework.
InthepresenceofJrgensen-Hayashicatalyst5a,thereactionproceededwelltoaordthecyclopentenederivatives130inmoderatetogoodyieldswithgoodenantioselectivities.
Thisalsoprovidesasimpleoperationalprocedurefortheenantioselectivesynthesisof(+)-rotundial130a(Scheme33).
FurtherexpansionofthescopeofMichaelacceptorstovinylsulfoneswasreportedbyAlexakisandco-workersrecently.
55Trans-4-hydroxyprolylamide133wasfoundtobetheoptimalcatalysttopromotetheintramolecularMichaeladditionofaldehydestovinylsulfone,aordingthedesiredproducts132ingoodyields,togetherwithgooddiastereos-electivitiesandenantioselectivities(Scheme34).
5.
MiscellaneousSomeelegantexampleshaveappearedforapplyingasymmetricorganocatalyticMichaelreactionsinthetotalsynthesisofnaturalproducts.
56Mostrecently,Fanandco-workers57reportedanunprecedentedMichaeladditionofa-cyanoke-tones134andacrylates135asthekeystepforthediversity-orientedasymmetricsynthesisofbioactivehydrodibenzofuranalkaloids.
Byusingbifunctionaltertiaryamine-thioureacatalyst30aor67c,highlyfunctionalisedbuildingblocks136withasterically-congestedaryl-substitutedquaternarycarbonatomwereobtainedinhighyieldsandexcellentenantio-selectivitiesafteronerecrystallisation.
Thebuildingblocks136werethentransformedto137withthecis-hydrodibenzo-furancorestructureunderanintramolecularketone-estercondensationandoxa-Michaelsequence.
ThreenaturalScheme31Scheme32Scheme33hydrodibenzofuranalkaloids,()-lycoramine,()-galanthamineand(+)-lunarine,wereconstructedonthebasisofthismethod(Scheme35).
TheorganocatalyticcascadereactionsinvolvingMichaeladditionhaveemergedaspowerfulstrategiesforthesynthesisofcomplexnaturalproductsandbioactivecompounds.
Sincethecascadereactionsoeradvantagessuchasprotecting-group-free,atomandstepeconomy,severalelegantexampleshavebeenproducedinorganocatalysisandtheprogresshasbeensummarisedrecently.
58Besides,theconjugateadditionsofnon-carbonnucleophilessuchasamines,59alcohols,60thiols61andphosphorus62leadingtotheformationofacarbon–heteroatombondviahetero-Michaeladditionhavebeenachieved,thedescriptionofwhichhave,however,notbeenincludedinthisreview.
6.
ConclusionInsummary,considerableprogressintheareaofasymmetricMichaelreactionshasbeenmaderecentlythroughthecombi-nationofvariousMichaeldonorsandacceptors.
Organo-catalysisprovedtobeoneofthemostecientmethodsforthetarget-anddiversity-orientedsynthesis,andmanysuccess-fulexamplesintheconstructionofimportantbuildingblocksfornaturalproductssynthesishaveemerged.
Furtherextensionoftheconceptstovinylogousaswellasintramolecularreactionsgivesvitalityinthisarea.
Hence,futuredevelopmentsinthiseldwillprobablyfocusonbroadeningthescope,exploitingnewapproachesanddevelopingnewconceptsoftheorganocatalyticasymmetricMichaelreaction,especiallytowardsthetarget-anddiversity-orientedsynthesis.
AcknowledgementsTheNationalNaturalFoundationofChina(no.
20972064and21172103)isgratefullyacknowledgedfornancialsupport.
Notesandreferences1(a)P.
I.
DalkoandL.
Moisan,Angew.
Chem.
,Int.
Ed.
,2004,43,5138;(b)A.
BerkesselandH.
Gro¨ger,AsymmetricOrganocatalysis:FromBiomimeticConceptstoApplicationsinAsymmetricSynthesis,Wiley-VCH,Weinheim,2005;(c)P.
I.
Dalko,EnantioselectiveOrganocatalysis,Wiley-VCH,Weinheim,2007;(d)B.
ListandJ.
W.
Yang,Science,2006,313,1584;(e)Specialissueonorganocatalysis,Chem.
Rev.
,2007,107,5413;(f)D.
W.
C.
MacMillan,Nature,2008,455,304;(g)J.
T.
Mohr,M.
R.
KroutandB.
M.
Stoltz,Nature,2008,455,323.
2(a)S.
B.
Tsogoeva,Eur.
J.
Org.
Chem.
,2007,1701;(b)D.
Almasi,D.
A.
AlonsoandC.
Najera,Tetrahedron:Asymmetry,2007,18,299;(c)J.
L.
Vicario,D.
BadiaandL.
Carrillo,Synthesis,2007,2065;(d)M.
Thirumalaikumar,Org.
Prep.
Proced.
Int.
,2011,43,67.
3(a)D.
R.
Spring,Org.
Biomol.
Chem.
,2003,1,3867;(b)T.
E.
NielsenandS.
L.
Schreiber,Angew.
Chem.
,Int.
Ed.
,2008,47,48;(c)S.
L.
Schreiber,Nature,2009,457,153;(d)W.
Galloway,A.
Isidro-LlobetandD.
R.
Spring,Nat.
Commun.
,2010,1.
4S.
L.
Zhu,S.
Y.
Yu,Y.
WangandD.
W.
Ma,Angew.
Chem.
,Int.
Ed.
,2010,49,4656.
5H.
Ishikawa,T.
SuzukiandY.
Hayashi,Angew.
Chem.
,Int.
Ed.
,2009,48,1304.
6X.
-L.
Liu,Z.
-J.
Wu,X.
-L.
Du,X.
-M.
ZhangandW.
-C.
Yuan,J.
Org.
Chem.
,2011,76,4008.
7(a)F.
Zhou,Y.
L.
LiuandJ.
Zhou,Adv.
Synth.
Catal.
,2010,352,1381;(b)J.
J.
Badillo,N.
V.
HanhanandA.
K.
Franz,Curr.
Opin.
DrugDiscoveryDev.
,2010,13,758.
8P.
Galzerano,G.
Bencivenni,F.
Pesciaioli,A.
Mazzanti,B.
Giannichi,L.
Sambri,G.
BartoliandP.
Melchiorre,Chem.
–Eur.
J.
,2009,15,7846.
9R.
J.
He,C.
H.
DingandK.
Maruoka,Angew.
Chem.
,Int.
Ed.
,2009,48,4559.
10X.
Li,Z.
G.
Xi,S.
Z.
LuoandJ.
P.
Cheng,Org.
Biomol.
Chem.
,2010,8,77.
11T.
Bui,S.
SyedandC.
F.
Barbas,J.
Am.
Chem.
Soc.
,2009,131,8758.
12R.
J.
He,S.
ShirakawaandK.
Maruoka,J.
Am.
Chem.
Soc.
,2009,131,16620.
13X.
Li,B.
Zhang,Z.
G.
Xi,S.
Z.
LuoandJ.
P.
Cheng,Adv.
Synth.
Catal.
,2010,352,416.
14Y.
H.
Liao,X.
L.
Liu,Z.
J.
Wu,L.
F.
Cun,X.
M.
ZhangandW.
C.
Yuan,Org.
Lett.
,2010,12,2896.
15X.
Li,S.
Z.
LuoandJ.
P.
Cheng,Chem.
–Eur.
J.
,2010,16,14290.
16X.
Li,Z.
G.
Xi,S.
Z.
LuoandJ.
P.
Cheng,Adv.
Synth.
Catal.
,2010,352,1097.
17X.
Li,S.
S.
Hu,Z.
G.
Xi,L.
Zhang,S.
Z.
LuoandJ.
P.
Cheng,J.
Org.
Chem.
,2010,75,8697.
18M.
Nielsen,C.
B.
Jacobsen,N.
Holub,M.
W.
PaixaoandK.
A.
Jrgensen,Angew.
Chem.
,Int.
Ed.
,2010,49,2668.
19M.
Nielsen,C.
B.
Jacobsen,M.
W.
Paixao,N.
HolubandK.
A.
Jrgensen,J.
Am.
Chem.
Soc.
,2009,131,10581.
20M.
W.
Paixao,N.
Holub,C.
Vila,M.
NielsenandK.
A.
Jrgensen,Angew.
Chem.
,Int.
Ed.
,2009,48,7338.
21N.
Holub,H.
Jiang,M.
W.
Paixao,C.
TiberiandK.
A.
Jrgensen,Chem.
–Eur.
J.
,2010,16,4337.
22A.
N.
R.
AlbaandR.
Rios,Chem.
–Asian.
J.
,2011,6,720.
23S.
Cabrera,E.
Reyes,J.
Aleman,A.
Milelli,S.
KobbelgaardandK.
A.
Jrgensen,J.
Am.
Chem.
Soc.
,2008,130,12031.
24Y.
Hayashi,K.
Obi,Y.
Ohta,D.
OkamuraandH.
Ishikawa,Chem.
–Asian.
J.
,2009,4,246.
25J.
Aleman,A.
Milelli,S.
Cabrera,E.
ReyesandK.
A.
Jrgensen,Chem.
–Eur.
J.
,2008,14,10958.
26D.
Uraguchi,Y.
UekiandT.
Ooi,Science,2009,326,120.
Scheme34Scheme3527H.
Jiang,M.
W.
Paixao,D.
MongeandK.
A.
Jrgensen,J.
Am.
Chem.
Soc.
,2010,132,2775.
28A.
N.
R.
Alba,X.
Companyo,G.
Valero,A.
MoyanoandR.
Rios,Chem.
–Eur.
J.
,2010,16,5354.
29A.
N.
R.
Alba,G.
Valero,T.
Calbet,M.
Font-Barda,A.
MoyanoandR.
Rios,Chem.
–Eur.
J.
,2010,16,9884.
30M.
B.
Cid,S.
Duce,S.
Morales,E.
RodrigoandJ.
L.
G.
Ruano,Org.
Lett.
,2010,12,3586.
31(a)S.
L.
You,Q.
CaiandM.
Zeng,Chem.
Soc.
Rev.
,2009,38,2190;(b)V.
Terrasson,R.
M.
deFigueiredoandJ.
M.
Campagne,Eur.
J.
Org.
Chem.
,2010,2635.
32Y.
Z.
Liu,R.
L.
ChengandP.
F.
Xu,J.
Org.
Chem.
,2011,76,2884.
33W.
Sun,L.
HongandR.
Wang,Chem.
–Eur.
J.
,2011,17,6030.
34R.
C.
FusoN,Chem.
Rev.
,1935,16,1.
35(a)G.
Casiraghi,L.
Battistini,C.
Curti,G.
RassuandF.
Zanardi,Chem.
Rev.
,2011,111,3076;(b)H.
-L.
CuiandY.
-C.
Chen,Chem.
Commun.
,2009,4479.
36S.
P.
Brown,N.
C.
GoodwinandD.
W.
C.
MacMillan,J.
Am.
Chem.
Soc.
,2003,125,1192.
37J.
F.
Wang,C.
Qi,Z.
M.
Ge,T.
M.
ChengandR.
T.
Li,Chem.
Commun.
,2010,46,2124.
38Y.
A.
Zhang,C.
G.
Yu,Y.
F.
JiandW.
Wang,Chem.
–Asian.
J.
,2010,5,1303.
39H.
C.
Huang,F.
Yu,Z.
C.
Jin,W.
J.
Li,W.
B.
Wu,X.
M.
LiangandJ.
X.
Ye,Chem.
Commun.
,2010,46,5957.
40A.
Quintard,A.
LefrancandA.
Alexakis,Org.
Lett.
,2011,13,1540.
41B.
M.
TrostandJ.
Hitce,J.
Am.
Chem.
Soc.
,2009,131,4572.
42M.
TeradaandK.
Ando,Org.
Lett.
,2011,13,2026.
43N.
E.
Shepherd,H.
Tanabe,Y.
J.
Xu,S.
MatsunagaandM.
Shibasaki,J.
Am.
Chem.
Soc.
,2010,132,3666.
44X.
Feng,H.
L.
Cui,S.
Xu,L.
WuandY.
C.
Chen,Chem.
–Eur.
J.
,2010,16,10309.
45Y.
Zhang,Y.
L.
Shao,H.
S.
XuandW.
Wang,J.
Org.
Chem.
,2011,76,1472.
46H.
C.
Huang,Z.
C.
Jin,K.
L.
Zhu,X.
M.
LiangandJ.
X.
Ye,Angew.
Chem.
,Int.
Ed.
,2011,50,3232.
47(a)M.
F.
A.
Adamo,E.
F.
Duy,D.
DonatiandP.
Sarti-Fantoni,Tetrahedron,2007,63,2684;(b)M.
F.
A.
AdamoandV.
R.
Konda,Org.
Lett.
,2007,9,303;(c)M.
F.
A.
Adamo,D.
Donati,E.
F.
DuyandP.
Sarti-Fantoni,J.
Org.
Chem.
,2005,70,8395.
48A.
Baschieri,L.
Bernardi,A.
Ricci,S.
SureshandM.
F.
A.
Adamo,Angew.
Chem.
,Int.
Ed.
,2009,48,9342.
49S.
Bertelsen,M.
Marigo,S.
Brandes,P.
DinerandK.
A.
Jrgensen,J.
Am.
Chem.
Soc.
,2006,128,12973.
50G.
Bencivenni,P.
Galzerano,A.
Mazzanti,G.
BartoliandP.
Melchiorre,Proc.
Natl.
Acad.
Sci.
U.
S.
A.
,2010,107,20642.
51M.
T.
HechavarriaFonsecaandB.
List,Angew.
Chem.
,Int.
Ed.
,2004,43,3958.
52(a)Y.
Hayashi,H.
Gotoh,T.
Tamura,H.
Yamaguchi,R.
MasuiandM.
Shoji,J.
Am.
Chem.
Soc.
,2005,127,16028;(b)M.
Kikuchi,T.
InagakiandH.
Nishiyama,Synlett,2007,1075.
53W.
J.
Nodes,D.
R.
Nutt,A.
M.
ChippindaleandA.
J.
A.
Cobb,J.
Am.
Chem.
Soc.
,2009,131,16016.
54E.
Marques-Lopez,R.
P.
Herrera,T.
Marks,W.
C.
Jacobs,D.
Ko¨nning,R.
M.
deFigueiredoandM.
Christmann,Org.
Lett.
,2009,11,4116.
55C.
Bournaud,E.
Marchal,A.
Quintard,S.
Sulzer-MosseandA.
Alexakis,Tetrahedron:Asymmetry,2010,21,1666.
56E.
Marques,R.
P.
HerreraandM.
Christmann,Nat.
Prod.
Rep.
,2010,27,1138.
57P.
Chen,X.
Bao,L.
-F.
Zhang,M.
Ding,X.
-J.
Han,J.
Li,G.
-B.
Zhang,Y.
-Q.
TuandC.
-A.
Fan,Angew.
Chem.
,Int.
Ed.
,2011,50,8161.
58(a)D.
Enders,C.
GrondalandM.
R.
M.
Huettl,Angew.
Chem.
,Int.
Ed.
,2007,46,1570;(b)X.
YuaandW.
Wang,Org.
Biomol.
Chem.
,2008,6,2037;(c)C.
Grondal,M.
JeantyandD.
Enders,Nat.
Chem.
,2010,2,167.
59D.
Enders,C.
WangandJ.
X.
Liebich,Chem.
–Eur.
J.
,2009,15,11058.
60C.
F.
NisingandS.
Bra¨ese,Chem.
Soc.
Rev.
,2008,37,1218.
61D.
Enders,K.
LuettgenandA.
A.
Narine,Synthesis,2007,959.
62D.
Enders,A.
Saint-Dizier,M.
I.
LannouandA.
Lenzen,Eur.
J.
Org.
Chem.
,2006,29.