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KeyLaboratoryofGreenChemistry&TechnologyMinistryofEducation,CollegeofChemistrySichuanUniversity2017-01-5CatalyticAsymmetricRearrangementReactionsUsingChiralN,N′-Dioxide-MetalComplexesChiralityisthespatialarrangementofpointsoratomsthatarenon-superimposableonitsmirrorimage.Characteristically,enantiomers(twomirrorimagesofamoleculethatcannotbesuperposedontoeachother)aredifferentcompounds.TheconceptofchiralityConceptsinAsymmetricSynthesisImportance:pharmaceuticals,agrochemicals,flavors,andmaterialsetc.adisastrousflaw!MainMethodsforthePreparationofOpticallyActiveOrganicCompounds10%72%18%Chiralpoolsynthesisandresolutionbiocatalysis18%10%72％AsymmetriccatalysisTheNobelPrizeinChemistry2001WilliamsS.KnowlesRyojiNoyoriK.BarrySharpless“fortheirworkonchirallycatalysedhydrogenation/oxidationreactions”AsymmetrichydrogenationAsymmetricoxidationAsymmetriccatalysiswithenzymes,chiralmetalcomplexes,andchiralorganocatalystshaveemergedassuccessfulandpowerfultoolsinasymmetricsynthesis.SomeChallengesinAsymmetricCatalysisSelectivity:Thereisnoonecatalystthatisuniversalforallsubstrates.Todesirecatalystdiversity.ReactivityandEfficiency:1-10mol%catalystloadingisnotpractical.Todesire0.1-0.01mol%orless.Catalystrecoveryandreuse.Mildreactionconditionsandothers……NewCatalystsandAsymmetricReactionswithHighEfficiencyandSelectivity.OurWork:ChiralLigandsandOrganocatalystsfromAminoAcids1999nowBIFUNCTIONALCATALYSIS“mostprivilegedcatalystspossessrigidstructureswithmultipleO-,N-,orP-containingfunctionalgroupsthatallowthemtobindstronglytoreactivemetalcenters”.Researchershavedesignedchiralcatalystsshowinggoodenantioselectivityoverawiderangeofdifferentreactionsas“privilegedchiralcatalysts”.RepresentativeChiralN-OxidesinAsymmetricReactions1.L.-X.Dai,Z.-H.Zhou,Y.-Z.Zhang,C.-Z.Ni,Z.-M.Zhang,Y.-F.Zhou,J.Chem.Soc.,Chem.Commun.1987,1760.2.DavidWenkert,R.B.Woodward,J.Org.Chem.1983,48,283.3.AndreiV.Malkov;PavelKocovský,Eur.J.Org.Chem.2007,29.4.G.Chelucci,G.Marineddu,G.A.Pinna,Tetrahedron:Asymmetry2004,15,1373.biquinolineN-oxidepyridineorquinoline-typeN-oxidesTheoxygen2pπelectronsareconjugatedwiththeN-heteroaromaticring.ThenitrogenoftheN-oxidemoietyisachiral.ChiralBiquinolineN,N’-Dioxidea.BoLiu,XiaomingFeng*,etal,Synlett2001,1501.b.ZhigangJiao,XiaomingFeng*,EurJ.Org.Chem.2003,3818.BifunctionalCatalystSystemY.-C.Shen,X.-M.Feng,G.-L.Zhang,Y.-Z.Jiang,Synlett.2002,1353.Y.-C.Shen,X.-M.Feng,Y.Li,G.-L.Zhang,Y.-Z.Jiang,Eur.J.Org.Chem.2004,129.titaniumcomplexofmonoN-oxideDiarylprolinol-basedstructurehypersiliconintermediateN-oxideisapproximatelytetrahedralwithchirality.DesignofBifunctionalC2-SymmetricN,N’-DioxideCompoundscombiningthekeycharacteristicsofthecatalystsformultidentatebifunctionalcatalysisSynthesisofChiralN,N’-DioxideAmidesInexpensiveConvenitenttomanipulateAmenabletoStructuralmodificationStableRepresentativeStructuresofChiralN,N’-DioxidesThestereoselectiveoxidationandformationofsix-memberedhydrogen-bondedringswereconfirmedbyNMRandX-rayanalysisofN,N’-dioxides.alkylchainalkylchainDiamine-linkerAryl-linkerBINOL-linkerNamingoftheligandsRepresentativeStructuresofChiralN,N’-DioxidesX-raystructureofL-PiPrX-raystructureofL-RiPrVariedstereo-arrangementofN,N’-dioxidesbearingdifferentaminoacidbackboneshowstheconformationalflexibilityofthecompounds.H-bondingH-bondingoppositesiteofthelinkersamesiteofthelinkerAsymmetricCyanosilylationofAldehydes,KetonesandIminesFurtherApplications?----ChiralLigandsScMgFeCoNiCuZnInAgYLaNdSmGdYbAwildvarietyofmetalcationscanassociatewithchiralN,N'-dioxidestoformefficientcatalysts,includingrare-earthmetals,thetransitionmetals,andmaingroupmetals.FurtherApplications?----ChiralLigandsAcc.Chem.Res.2011,574;Chem.Rev.2011,6947;Org.Chem.Front.2014,1,298.Chemoselectivity----IntrinsicproblemoftheclassicRoskampreactionStereoselectivestrategy:AsymmetricRoskampReactionThereactionprocessmightundergothreerearrangementpathwaysoncethediazoniumintermediategenerated.Thatistheshiftcompetitionofhydrogen,oxygenoralkylgroup.Roskampreactionusing-alkyl--diazoesterscouldprovidechiral-alkyl--ketoesters.Racemizationoftheproductisabigproblem.TwostereoselectiveexamplesreportedbyProf.Maruokaentryligandmetaltime(h)yield(%)ee(%)1L-PiPr2Zn(OTf)2298552L-PiPr2Sm(OTf)3/Y(OTf)3/La(OTf)3/Yb(OTf)329N.R.-3L-PiPr2Sc(OTf)3795784L-PrPr2Sc(OTf)3790751,2-HshiftSc1HNMRafterchromotographyseparation1HNMRafterflashfiltrationFlashfiltrationisenoughforpurifyoftheproduct.Noenolesterexistedinaproticsolvent.entryligandadditiveL:ScIIIx(mol%)time(h)ee(%)yield(%)1L-RiPr2-1:15794972L-RiPh-1:152940103bL-RiPr23ÅMS1:15294974b,c,dL-RiPr23ÅMS1:1.20.05295975b,c,eL-RiPr23ÅMS1:1.20.01569580aL/Sc(OTf)3(1/1),0.1mmol1aand0.1mmol2ain0.5mLCH2Cl2at-20oC.b3ÅMS(10.0mg)wasadded.cL-RiPr2/Sc(OTf)3(1/1.2),1.0mmol1aand1.0mmol2a.d0.2mLCH2Cl2wasused.e0.1mLCH2Cl2wasused.Li,W.;Wang,J.;Wang,W.T.;Lin,L.L.;Liu,X.H.;Feng,X.M.J.Am.Chem.Soc.2010,132,8532.Aliphaticaldehydesfailed.EnantioselectiveRoskampreactioncatalyzedbyoxazaborolidiniumionProf.D.H.Ryu*,Angew.Chem.Int.Ed.2012,51,8322.Roskamp-Feng反应(Synfacts2012,8