有机反应机理第10章2.

15.4醇的氧化5.4.1用二甲亚砜氧化5.4.2用铬试剂氧化5.4.3用高价碘化物氧化5.4.4催化氧化（选讲）25.4.1用二甲亚砜氧化二甲亚砜可与各种亲电试剂反应生成活性锍盐(sulfoniumsalt)活性锍盐与醇反应生成烷氧基锍盐烷氧基锍盐发生消除，生成醛或酮3二甲亚砜氧化醇为醛、酮的过程H3CSH3COEH3CSH3COER1R2OHH2CSH3CR1R2OHHBHBH2CSH3CR1R2OHR1R2OaldehydeorketoneH3CSCH2H+4解释二甲亚砜氧原子的亲核性前几章是否碰到过二甲亚砜作为亲核试剂的反应5用二甲亚砜氧化的典型反应Pfitzner-Moffatt(普菲茨纳-莫法特)氧化,1963Albright-Goldman氧化，1965Parikh-Doering（帕瑞克-多林）氧化，1967Swern（斯文）氧化，1978这些氧化反应的区别在哪里？6R1R2OHR1R2OR1R2OHDMSO/DCC/acidsolventPfitzner-Moffatt1963R1R2OHDMSO/Ac2OsolventAlbright&Goldman1965R1R2OHDMSO/TFAAor(COCl)2/NEt3solventSwern,1976&1978DMSO/pyridine-SO3/NEt3/solventParikh&Doering,19677Swern氧化DMSO/TFAAor(COCl)2/NEt3solvent1976年，DSwern发现TFAA能在－50℃下活化DMSO氧化醇为醛酮R1R2OaldehydeorketoneR1R2OH1oor2oalcohol1978年又发现草酰氯作为活化剂较TFAA更有效8Swern氧化的机理（TFAA活化）F3COCF3OOCH3SCH3OH3CSOCF3CH3OR1R2OH－CF3COOHH3CSOR2CH2HR1HF3COCF3OOCH3SH3CO为什么DMSO不能一步取代三氟乙酸根离子？9Swern氧化的机理（TFAA活化，续）H3CSOR2CH2HR1HNEt3H3CSOR2CH2HR1R1R2OaldehydeorketoneH3CSCH2H+讨论中间体内鎓盐结构10中间体的Pummerer重排OCF3OH2CSCH3H2CSOCF3CH3OH-eliminationOCF3OH2CSCH3OCF3O+11Swern氧化的机理（草酰氯活化）ClClOOH3CSOCH3OClOClCH3SCH3Cl+CO2+COClClOOCH3SCH3OCH3SCH3O12Swern氧化的机理（草酰氯活化，续）CH3SCH3ClR1R2OHH3CSOR2CH2HR1HNEt3H3CSOR2CH2HR1R1R2OaldehydeorketoneH3CSCH2H+13Swern氧化的特点无溶剂易爆炸!!!常在二氯甲烷中反应低温反应（－78℃）DMSO与草酰氯的起始加成物在－60℃以上不稳定TFAA作活化剂－30℃以上会发生Pummerer重排14Swern氧化法的改进XunHeandTakHangChan.Newnon-volatileandodorlessorganosulfurcompoundsanchoredonionicliquids.RecyclablereagentsforSwernOxidation.Tetrahedron,200662(14):3389–3394二甲亚砜，二甲硫醚有恶臭，成本高以下文献提出将亚砜负载在离子液体上，无恶臭，可循环使用15a:n=1b:n=2c:n=516Swern氧化合成vapiprostNHOOOCC6H4C6H5CO2H伐哌前列素：抗血小板凝聚17DanielLednicer.Strategiesfororganicdrugsynthesisanddesign,p16,NewYork:JohnWiley&Sons,Inc,1998参考文献18NHOOOCC6H4C6H5CO2H1.DMSO/TFAA2.DIBAL-HNHOOOCC6H4C6H5CO2H19Swern氧化合成(+)-asteltoxinAmycotoxin，毒枝菌素OOHMeMeHOOHOMeOMeO20Eom,K.D.,Raman,J.V.,Kim,H.,Cha,J.K.TotalSynthesisof(+)-Asteltoxin.J.Am.Chem.Soc.2003,125(18):5415-5421.参考文献21OOPMBMeOOHMeTIPSCl80%OOPMBMeOOTIPSMeOsO4/NMO85%OOPMBMeOOTIPSMeMeHOHO1.DMSO/(COCl)2/DCM2.EtMgBrOOPMBMeOOTIPSMeMeHOOH22OOPMBMeOOTIPSMeMeHOOHOOPMBOHMeMeHOOHOOPMBCHOMeMeHOOHDMSO/(COCl)2/DCMsteps23OOPMBCHOMeMeHOOHiPrOPOEtOOiPrO79%OOPMBMeMeHOOHCO2Et1.DIBAL-H,78%2.DDQ,80%3.MnO2,86%OOHMeMeHOOHCHOOPOOMeOMeOOMeMeLiHMDSOOHMeMeHOOHOMeOMeO24Pfitzner-Moffatt氧化DMSO/DCC/acidsolventPfitzner-Moffatt1963反应通式R1R2OH1oor2oalcoholR1R2Oaldehydeorketone25Pfitzner-Moffatt氧化反应特点DMSO的活化剂DCC需过量（3倍以上），后处理时加草酸可除去过量的DCC反应必须有中等强度的酸催化，如H3PO4,二氯乙酸，强酸吡啶盐等，强酸对反应有阻碍作用副产物二环己基脲较难除去，用水溶性的碳二亚胺替代DCC可克服这一问题26Pfitzner-Moffatt氧化机理NCNRRHNCNRRHCH3SCH3ONCNRRHOSCH3CH3DMSO的活化27Pfitzner-Moffatt氧化机理（续）NCNRRHOSCH3CH3R1R2OHHH2CSONRHNROR2H3CR1H3CSOR2CH2HR1RNNROHH+28Pfitzner-Moffatt氧化机理（续）R1R2OaldehydeorketoneH3CSCH2H+H3CSOR2CH2HR129Pfitzner-Moffatt氧化反应操作将二环己基碳二亚胺（DCC)溶于DMSO中，然后加入醇和催化酸(磷酸，三氟乙酸，吡啶-磷酸等）进行反应30Pfitzner-Moffatt氧化反应实例ONHNOHOOAcOONHNOOHCOAcODMSO/DCC/H3PO4r.t.90%315.4.2用铬试剂氧化典型反应：Jones氧化1946年，ERHJones发现三氧化铬与稀硫酸的溶液可将伯醇氧化成羧酸，仲醇氧化成酮32R1R2OHCrO3orCr2O72－/acidH2O/acetoneR1R2OR1-2=alkyl,arylketoneJonesoxidation,1946R=alkyl,aryl,alkenylROHCrO3orCr2O72－/acidH2O/acetoneRHOROHOcarboxylicacidCrO3orCr2O72－/acidH2O/acetonealdehyde33Jones氧化的机理稀溶液中铬酸以单体H2CrO4存在浓溶液中铬酸以二聚体H2Cr2O7存在反应中醇先与铬酸形成铬酸酯,再脱氢生成产物动力学同位素效应测定表明脱氢是速率控制步骤34CrOHOOOHR1R2OH+－HOHCrOHOOOR2R1HR1R2OHCrO3+HOH2+HOHrds碱促进分子间脱氢机理35CrOHOOOHR1R2OH+－HOH无碱促进分子内脱氢机理CrOHOOOR2R1HR1R2OH2CrO3+36Jones试剂的制备和氧化操作Jones试剂的制备实例Jones氧化操作将26.7gCrO3溶于23mL浓硫酸中，加水稀释到100mL0~20oC往醇的丙酮溶液中滴加Jones试剂37Jones试剂氧化仲醇的实例OHOJonesoxidation75%38Jones氧化合成石斛碱石斛碱,(-)-dendrobineOOHNH3C39参考文献Sha,C.-K.,Chiu,R.-T.,Yang,C.-F.,Yao,N.-T.,Tseng,W.-H.,Liao,F.-L.,Wang,S.-L.TotalSynthesisof(-)-Dendrobinevia-CarbonylRadicalCyclization.J.Am.Chem.Soc.1997,119,4130-4135.40OOHOHN3CrO3/H2SO4/H2Oacetone,r.t.,1.5h,94%OOHON31.PPh3/THF,r.t.,12h2.NaBH3CN/AcOH/MeOHr.t.,12hStaudingerreactionOOHHN(CH2O)n/HCO2H/H2O120oC,12h42%for3stepsOOHNH3C41Staudinger反应，1919R1NNN+PR3R1NPR3R1NNNPR3NNNPR3R1－N242Staudinger反应产物的转化R1NPR3R1NH2R3PO+H2OR1OHOR3R2NR1R3R2OOR2NR1HR2XOR2XNR143GeneralfeaturesofJonesoxidationTheoxidationisusuallycarriedoutinacetone,whichservesadualpurposeItreactswithanyexcessoxidantsoitprotectstheproductfromoveroxidationItdissolvesmostorganicsubstrates,and44PrimaryalcoholsareconvertedtocarboxylicacidswiththeintermediacyofaldehydesAldehydescanbeisolatedbydistillationsometimesifthealdehydeisvolatile45Allylicandbenzylicalcoholsareefficientlyoxidizedtothecorrespondingaldehydeswithlittleornoover-oxidationIsolateddoubleandtriplebondsremainunchangedbut,-unsaturatedaldehydeproductsmayundergodoublebondisomerization46ForparticularlyacidsensitiveorotherwisedelicatesubstratestheuseofthestronglyacidicJonesreagentisclearlynotthebestmethodofoxidation47Jones氧化的改进Collins试剂氧化（SarettandCollins,1953~1968)制备CrO3吡啶络合物CrO3(pyridine)2(Collines试剂）在二氯甲烷中氧化1oor2oalcoholaldehydeorketoneR1R2OR1R2OHCrO3-pyridineDCM48Collines试剂氧化实例CH3(CH2)5CH2OHCH3(CH2)5CHOCrO3(Py)2/CH2Cl225oCheptan-1-olheptanal70~84%可氧化伯醇为醛49PCC和PDC氧化（Corey,1975and1979)R1R2OR1R2OHPCCorPDCDCM1oor2oalcoholaldehydeorketonePCC：氯铬酸吡啶鎓盐（弱酸性）PDC：重铬酸吡啶鎓盐（中性）50氧化铝负载PCC的制备2.5g(25mmol)CrO3溶于5mL