Enantioselective Amino Acid Synthesis by Chiral Ph

EnantioselectiveAminoAcidSynthesisbyChiralPhase-TransferCatalysisKeijiMaruoka*andTakashiOoiDepartmentofChemistry,GraduateSchoolofScience,KyotoUniversity,Sakyo,Kyoto606-8502,JapanReceivedJanuary16,2003ContentsI.Introduction3013II.AminoAcidSynthesiswithAchiralPhase-TransferCatalysts3013III.EnantioselectiveAlkylationofGlycineDerivativesforR-Alkyl-R-aminoAcidSynthesis3014IV.EnantioselectiveAlkylationofGlycineandR-Alkyl-R-aminoAcidDerivativesforR,R-Dialkyl-R-aminoAcidSynthesis3021V.DiastereoselectivePeptideAlkylation3023VI.EnantioselectiveMichaelAdditionofGlycineDerivatives3026VII.EnantioselectiveDirectAldolReactionofGlycineDerivatives3026VIII.Conclusion3027IX.References3027I.IntroductionTheR-aminoacids,whichareusuallyformulatedasH2NCH(R)CO2Hdespitetheirzwitterionicnature,arebyfarthemostimportant,numerous,anddiversefamilyofthenaturallyoccurringaminoacids.Al-thoughasetofonly19togetherwiththeheterocyclicaminoacidprolinecomprisesthebuildingblocksfromwhichpolypeptidechainsareassembledunderge-neticcontrol,thetotalnumberofR-aminoacidsidentifiedasoccurringfreeorincorporatedinnaturalproductsofanimals,plants,andmicroorganismsisestimatedinthehundreds,andthelistofsuchR-aminoacidsgrowsallthetime.ThemajorityofthesenaturallyfoundR-aminoacidshavetheLconfigurationattheR-carbon.ManynaturalR-aminoacidsoftheDseriesarealsoencounteredinnon-proteincompoundsofplants,fungi,andmicroorgan-ismsbutnotgenerallyinanimalsandneverinanyprotein.Awidevarietyofmethods,whichareinprinciplegeneral,areavailableforthesynthesisofR-aminoacids.1SomeofthemincludetheaminationofR-haloacids,theStreckersynthesis,andapproachesthroughhydantoinsandoxazolones,whichweredevelopedintheearlydaysofaminoacidchemistrybutstillretaintheirimportance.Severalmodernelaborationsoftheserouteshavebeendeveloped.Synthesesinwhichtheaminogroupisintroducedbyreductionorrear-rangementhavealsobeenavailableforalongtime.Despitethegreatvarietyofthewell-triedmethods,thedevelopmentofnewgeneralstrategiesisstillanactivefield.Inaddition,considerableefforthasbeenpaidinthedevelopmentofasymmetricmethodologiesbycertainchiralcatalystsintheR-aminoacidfield.Ourmainconcerninthisreviewhasbeentoil-lustratetherangeofasymmetricapproachesavail-ableforthelaboratorypreparationofopticallyactiveaminoacidsbyusingchiralphase-transfercata-lysts.2,3II.AminoAcidSynthesiswithAchiralPhase-TransferCatalystsPhase-transfercatalysisisaveryusefulapproachthattypicallyinvolvessimpleexperimentalopera-tions,mildreactionconditions,inexpensiveandenvironmentallybenignreagentsandsolvents,andlarge-scalereactions.Initially,achiralphase-transfercatalystscanbeutilizedtosynthesizevarioustypesofR-aminoacids.Forexample,azideanionortrif-luoroacetamidereactswithR-bromoestersunderphase-transferconditionstofurnishR-aminoacidprecursors.4,5Achiralphase-transfercatalystsarealsoemployableforconversionofR-aminoacidstothecorrespondingesters,6,7amides,8,9anddidehy-droaminoacidderivatives.10-12AlkylationofglycinederivativesisaverypowerfulwayofpreparingR-alkyl-R-aminoacids.Benzophe-noneiminesofglycineestersandaminoacetonitrilearefrequentlyutilizedasprotectedglycinederiva-tivesforphase-transferalkylations.AstableSchiffbasewasderivedfromglycineesterandbenzophe-noneunderforcingconditions(tolueneorxylenerefluxwithcatalyticBF3âOEt2).13,14Phase-transferalkylationofsuchaSchiffbasewithtetrabutyl-ammoniumhydrogensulfateandalkylhalidein10%aqueoussodiumhydroxide/methylenechlorideandsubsequentacidhydrolysisoftheresultingalkylatedSchiffbaseprovidesthecorrespondingaminoacid(eq1).Thisapproachisapplicabletothepolyhalophen-ylalaninesynthesis.15Benzophenoneiminesandbenzaldehydeiminesofglycineesterscanbeutilizedformonoalkylation,dialkylation,Michaeladdition,andaldolreactionundersolid-liquidphase-transfercatalysis.16,173013Chem.Rev.2003,103,3013-302810.1021/cr020020eCCC:$44.00©2003AmericanChemicalSocietyPublishedonWeb06/13/2003Later,thetransiminationofglycineesterwithbenzophenoneimineasahighlyreactivebenzophe-noneequivalenthasbeendeveloped(eq2).Thismildprocedureisemployableforthepreparationofvari-oustypesofbenzophenoneiminederivatives.15Benzophenoneimineofaminoacetonitrileisalsoutilizedasaprotectedglycinederivative.Thecata-lyticphase-transferalkylationoftheSchiffbaseiscarriedoutwithbenzyltriethylammoniumchloride(BTEAC)asthephase-transfercatalystand50%aqueousNaOHastheaqueousphase(eq3).18SynthesisofopticallyactiveR-aminoacidshasbeenrealizedwithchiralsubstratessuchaschiraliminesofglycineesters,benzophenoneimineofchiralgly-cineesters,amidesandimidesderivedfromchiralalcohols,chiralamines,andchiralimidazolidino-nes.19,20Benzophenoneiminesofglycinederivativesup-portedonasolublepoly(ethyleneglycol)(PEG)wassmoothlyalkylatedwithvariouselectrophilesinthepresenceofacarbonatebaseinacetonitrile(eq4).21Thepresenceofthepolymerprovidedaphase-transfercatalysisenvironmentwhichmarkedlyac-celeratesthereaction.Aftercleavagefromthepoly-mer,R-aminomethylesterscanbegeneratedingoodyields.III.EnantioselectiveAlkylationofGlycineDerivativesforr-Alkyl-r-aminoAcidSynthesisAsymmetricsynthesisofR-aminoa