2012药物合成反应课件Oxidation6.ppt

Fudan University第六章第六章 氧化反应氧化反应Chapter 6-Oxidation ReactionFudan UniversityOxidating ReagentFudan University1.Oxidation of AlkaneSelective oxidation of saturated alkane is very difficult!Fudan University1.Oxidation of AlkaneReactivity:Primary Secondary TertiaryFudan UniversityBenzylic OxidationCerium(IV)ammonium nitrate（CAN）Oxidation to alcohol/esterFudan UniversityBenzylic OxidationOxidation to aldehydeFudan UniversityBenzylic OxidationEtard ComplexEtard Complex:Chromyl chloride/alkane 2:1Oxidation to ketoneFudan UniversityOxidation of KetoneFudan UniversityOxidation of KetoneFudan UniversityOxidation of KetoneFudan UniversityOxidation of Allylic CarbonFudan UniversityRiley OxidationFudan UniversityRiley Oxidation MechanismFudan UniversityRiley Oxidation ApplicationsMehta,G.,Shinde,H.M.Tetrahedron Lett.2003,44,7049-7053.Frstner,A.,Gastner,T.Org.Lett.2000,2,2467-2470.Fudan UniversityAllylic OxidationCollins ReagentDouble bond shiftFudan UniversityAllylic OxidationVO(OR)Cl2Fudan UniversityOxidation of Alcohol1.Oxidations of Primary and Secondary AlcoholsIntermolecularIntramolecularFudan UniversityOxidation of AlcoholFudan UniversityOxidation of AlcoholFormation of carbonyl compoundsJones oxidation:Cheap,easy to carry outsuitable for robust substrates on a big scale.Neither suitable for very acid sensitive substrates,nor for the preparation of many aldehydes.Collins oxidation:Cheap,but under anhydrous conditions.Produce very good yields of aldehydes and ketones in uncomplicated substrates.PDC and PCC are more expensive reagents that normally guaranteethe best results in difficult cases.Fudan UniversityOxidation of Alcohol-JonesFudan UniversityJones OxidationFudan UniversityJones OxidationWaizumi,N.,Itoh,T.,Fukuyama,T.J.Am.Chem.Soc.2000,122,7825-7826.Crimmins,M.T.,Jung,D.K.,Gray,J.L.J.Am.Chem.Soc.1993,115,3146-3155.Fudan UniversityOxidation with MnFudan UniversityOxidation with Ag/PbFudan UniversityOxidation with DMSODMSO-DCC(Pfitznor-Moffatt)DCC is the most widely used activating agent that needs to beapplied in excess(usually 3 equivalents or more)the oxidation only works with catalysts that are only moderately acidic compounds such as ortho-phosphoric acid(H3PO4),dichloroacetic acid andthe pyridinium salts of strong acidsFudan UniversityPfitznor-Moffatt OxidationFudan UniversityPfitznor-Moffatt OxidationSmith,A.B.,III,et al.J.Am.Chem.Soc.1992,114,1438-1449.Ichikawa,S.,et al.J.Am.Chem.Soc.1999,121,10270-10280.Fudan UniversityAlbright-Goldman OxidationSuitable for oxidation of hindered alcoholFudan UniversitySwern OxidationFudan UniversitySwern OxidationHillier,M.C.et al.J.Am.Chem.Soc.1999,121,866-867.Cha,J.K.et al.J.Am.Chem.Soc.2003,125,5415-5421.Fudan UniversityParikhDoering(Sulfur Trioxide-Mediated Moffatt Oxidation)Fudan UniversityCorey-Kim Oxidation Fudan UniversityCorey-Kim Oxidation Kuwajima,I.et al.J.Am.Chem.Soc.2003,125,1498-1500.Zubieta,J.et al.J.Org.Chem.1988,53,3439-3450.Fudan UniversityHypervalent Iodine-Dess-Martin OxidationFudan UniversityHypervalent Iodine-Dess-Martin OxidationNicolaou,K.C.et al.Org.Lett.1999,1,63-66.IBX(o-iodoxybenzoic acid)Fudan UniversityLey OxidationTetrapropylammonium perruthenate(TPAP)Fudan UniversityLey OxidationKeck,G.E.,Knutson,C.E.,Wiles,S.A.Org.Lett.2001,3,707-710.Hu,T.,Panek,J.S.J.Org.Chem.1999,64,3000-3001.Fudan UniversityOppenauer OxidationFudan UniversityOppenauer OxidationSternbach,D.D.,Ensinger,C.L.J.Org.Chem.1990,55,2725-2736.Kocovsky,P.,Baines,R.S.Tetrahedron Lett.1993,34,6139-6140.Fudan UniversityAlcohol Oxidation to Carboxylic AcidFudan UniversityOxidation of DiolFudan UniversityCriegee OxidationFudan UniversityCriegee OxidationMoricz,A.,Gassman,E.,Bienz,S.,Hesse,M.Helv.Chim.Acta 1995,78,663-669.Biju,P.J.,Rao,G.S.R.S.Tetrahedron Lett.1999,40,9379-9382.Fudan UniversityOxidation of DiolFudan UniversityOxidation of Aldehyde/KetoneDakin OxidationFudan UniversityDakin OxidationLyttle,M.H.,Carter,T.G.,Cook,R.M.Org.Process Res.Dev.2001,5,45-49.Fudan UniversityOxidation of OlefinFudan UniversityOxidation of OlefinFudan UniversityOxidation of OlefinFudan UniversityPrvost Reaction.Fudan UniversityPrvost Reaction.Fudan UniversitySharpless Asymmetric EpoxidationFudan UniversitySharpless Asymmetric EpoxidationHoye,T.R.,Ye,Z.J.Am.Chem.Soc.1996,118,1801-1802.Paterson,I.,De Savi,C.,Tudge,M.Org.Lett.2001,3,3149-3152.Fudan UniversityShi Asymmetric EpoxidationFudan UniversityShi Asymmetric EpoxidationHoard,D.W.,et al.Org.Lett.2002,4,1813-1815.Fudan UniversityJacobsen-Katsuki EpoxidationFudan UniversityJacobsen-Katsuki EpoxidationLynch,J.E.,Choi,W.B.,Churchill,H.R.O.,Volante,R.P.,Reamer,R.A.,Ball,R.G.J.Org.Chem.1997,62,9223-9228.Boger,D.L.,McKie,J.A.,Boyce,C.W.Synlett 1997,515-517.Fudan UniversitySharpless Asymmetric AminohydroxylationFudan UniversitySharpless Asymmetric AminohydroxylationDihydroxylationArmstrong,A.,et al.J.Org.Chem.2000,65,7020-7032.Cao,B.,Park,H.,Joullie,M.M.J.Am.Chem.Soc.2002,124,520-521.Fudan UniversitySharpless Asymmetric DihydroxylationFudan UniversitySharpless Asymmetric DihydroxylationFudan UniversityOxidation of OlefinLemieux reagent（NaIO4:KMnO4=6:1）:Fudan UniversityWacker OxidationFudan UniversityWacker OxidationOConnor,P.D.,Mander,L.N.,McLachlan,M.M.W.Org.Lett.2004,6,703-706.Fudan UniversityOxidation of AromaticsFremy Salt:ON(SO3K or Na)2Fudan UniversityOxidation of AromaticsFudan UniversityDehydrogenationFudan UniversityDehydrogenationFudan UniversityDehydrogenationFudan UniversityOxidation of AmineFudan UniversityOxidation of AmineFudan UniversityKornblum OxidationFudan UniversityKornblum OxidationFischer,B.,Kabha,E.,Gendron,F.-P.,Beaudoin,A.R.Nucleosides,Nucleotides&Nucleic Acids 2000,19,1033-1054.Fudan University Oxidation of SulfurFudan UniversityFleming-Tamao OxidationFudan UniversityFleming-Tamao OxidationVanecko,J.A.,West,F.G.Org.Lett.2002,4,2813-2816.Sun,P.,Sun,C.,Weinreb,S.M.J.Org.Chem.2002,67,4337-4345.