不对称羟胺化反应

醛酮-胺氧化，羟胺化反应研究进展报告人：黄俊2008.9.26光活性的α-羟基醛酮结构单元存在于很多重要的天然产物中，而且是很重要的合成子。醛酮的α-羟胺化反应是构建光活性的α-羟基醛酮结构单元的一个很新颖的方法。R1XR3R2NOR1OONHPhR2R3R1ONPhR2R3OHX=OLi,OSnBu3,NR2,OTMSHisashiYamamotowasborninKobe,Japan,in1963.HereceivedhisBachelor’sdegreefromKyotoUniversityin1967,wherehegothisstartinaresearchgroupheadedbyProf.H.Nozaki.ProfessorYamamotoreceivedhisPh.D.fromHarvardUniversityundermentorshipofCorey.YamamotohasbecomeawareoftheimportanceofchiralLewisacidsinasymmetricsynthesis.In1985,hefirstintroducedbinaphtholasaligandforchiralLewisacidcatalysts.Thisworkwastheforerunnerofavastamountofpresent-dayresearchonthebinaththolbasedchiralLewisacidcatalyst.Morerecently,silvercatalyzedeneandaldolreactionswerereportedwhichareremarkablyeffectiveinaseriesofasymmetrictransformations.Todate,ProfessorYamamotohasco-authoredover400publicationsand100reviews.HisashiYamamotoHisashiYamamoto’soutstandingworkonnitrosoaldolrecation[1].Momiyama,N.;Yamamoto,H.Angew.Chem.Int.Ed.2002,41,2986.[2].Momiyama,N.;Yamamoto,H.J.Am.Chem.Soc.2003,125,6038.[3].Momiyama,N.;Yamamoto,H.J.Am.Chem.Soc.2005,127,1080.[4].Momiyama,N.;Torii,H.;Saito,S.;Yamamoto,H.Pans2005,101,5374.[5].YamamotoY.;Momiyama,N.;Yamamoto,H.J.Am.Chem.Soc.2004,126,5962.[6].Momiyama,N.;Yamamoto,H.Org.Lett2004,126,5962.[7].Momiyama,N.;Yamamoto,H.J.Am.Chem.Soc.2004,126,5360.ArmandoCordova:TheArrheniusLaboratoryofStockholmUniversity[1].Bøgevig,A.;Sundén,H.;Córdova,A.Angew.Chem.Int.Ed.2004,43,1109.[2].Córdova,A.;Johansson,M.;Bøgevig,A.;Sundén,H.;Chem.Eur.J.2004,10,3673.[3].Sundén,H.;Dahin,N.;Ibrabem,I.;Adolfsson,H.;Córdova,A.Teterahedron.Letters.2005,46,3385.手性lewis酸催化的a-胺氧化反应Angew.Chem.Int.Ed2002,41,2986Yamamoto’sworkYield:37-94%TMSOR1R3R2NOOR1R1R2ONHPh0℃,1hEt3SiOTf(5mmol%)XR1R3R2NOOR1R1R2ONHPh(R)-BINAP-78℃,2hTHFAgOTfOSnR395%yield,97%eeOSnR396%yield,95%ee94%yield,87%ee92%yield,90%ee96%yield,85%ee93%yield,92%ee95%yield,82%ee92%yield,94%eePhOSnR3R3SnOOSnR3R3SnOOSnR3OSnR3Yamamoto’sworkJ.Am.Chem.Soc2003,125,6038NONR1RRR1OOHOHcat=30mol%cat-88--78℃,12h()nRR()nOONHPhyield:69-89%;ee:70-93%Yamamoto’sworkJ.Am.Chem.Soc2005,127,1080脯胺酸及其衍生物催化的a-胺氧化反应Angew.Chem.Int.Ed2003,42,4247ZhongguofuandMacmillan’sworkL-proline(20mol%)DMSO,RT20min,thenNaBH4,EtOHNOROROHONHPhyield:54-86%;ee:94-99%.J.Am.Chem.Soc2003,125,10808HayashiandCordova’sworkAngew.Chem.Int.Ed2004,43,1109Angew.Chem.Int.Ed2004,43,1112yield:64-91%;ee≥99%yield:44-96%;ee≥99%R1OR2NOL-prolineR1OR2ONHPhHayashi’swork:NHCOOHTBSOOR1R2NO10%1OR1R2ONHPh1DMFyield:45-78%;ee:98-99%Adv.synth.catal2004,346,1435NHOR1R2NO20%CATOR1R2ONHPhDMSO,RTNHSOOCF3subsubyieldeeOOOOOOO8499869471999897Tetrahedronletter45(2004)7235NHONHOR1NO10%CATDMSO,RTSOOMeROR1RONHPhsubyieldeeOOHOOO809974669899O5499Tetrahedronletters2005,46,3385.NHNHNNNTetrahedronletter47(2006),9067NOCAT(20mol%)DMSO,RT20min,thenNaBH4,EtOHR1OR2R1OR2ONHPhNHNHNNNyieldeesubOOOOOOO948775676569999999989898Yamamoto’sworkPans2005,101,5374.J.Am.Chem.Soc2006,128,6046Maruoka’swork手性Lewis碱催化的醛酮α-羟胺化反应yield:70-90%;ee:97-99%NHCPh2OHCPh2OHNORO10mol%cat,NaBH4,EtOHROHNOHPhcat=手性Lewis酸催化的醛酮α-羟胺化反应J.AM.CHEM.SOC126(2004),5360OSnBu395%yield,99%eeOSnBu394%yield,77%eeOSnBu397%yield,98%ee90%yield,86%ee96%yield,97%eePhBu3SnOOSnBu3R1Bu3SnOR3R2NO(R)-BINAPEtOCH2CH2OEt-78℃,2hR1ONPhR2R3OH(AgOTf)2手性Lewis碱催化的醛酮α-羟胺化RHONO10%CATPhCH3,2-3dRHONPhHONaBH4OOHOsubyieldee(%)(%)HOHOButHOPrtHO74595346554669597133Chem.Commun2006,429NHNHOOHPhPhMechanism:Org.Lett.2002,4,3579SummaryandOutlook:Thecatalytic,asymmetricα-aminationandoxygenationofcarbonylcompoundsrepresentsavaluableadvanceinsyntheticmethodology.AdeeperunderstandingofthemechanismandthefactorsthatgovernOversusNselectivitywithnitrosocompoundswillallowforinnovationincatalystdesign.Inaddition,moreconvenientelectrophilicsourcesofnitrogenandoxygenalongwithbroadenedandgeneralsubstratescopewouldbeawelcomeadvance.Thanks!