偶联反应小结ppt课件

.,偶联反应Cross-CouplingReaction,.,经典反应式,.,.,Kumada,Suzuki,Stille,Negishi,Hiyamacoupling(C-CFormation：C-X+C-M)Buchwald-Hartwigcoupling(C-N,C-O,C-SFormation:C-X+Nu(N,O,S)-H)a-ArylationofKetone(C-CFormation:C-X+C-H)Heck,Sonogashiracoupling(AlkeneandalkyneFormation:C-X+C-H),.,GeneralMechanism,.,Kumada,Kumada-CorriuCoupling,1960年Chatt和Shaw:,1970年Uchino等:,.,Sp3C-Xsubstrate?,.,.,配体的影响,.,.,格氏试剂上烷基部分的异构化,.,.,.,.,.,Fe-catalystLowinitialtemperature(-20C)isbeneficial,Molander,G.A.et.al.TetrahedronLett.1983,24,5449.,Newdevelopmentofthecatalyst,.,Arylchlorides,triflatesandtosylatesarebettersubstratesthanarylbromidesandiodides,Frstner,A.et.al.Angew.Chem.Int.Ed.Engl.2002,41,609.,.,-Hydrideeliminationandhomocouplingarethemajorsetbackwiththecross-couplingof1oand2oalkylsubstrateswitharylGrignardreagents,Hayashi,T.et.al.Org.Lett.2004,6,1297.,*Amountafter0.05mmol(equivalenttocatalyst)subtracted.,AlkylDerivativesasSubstrate,.,AlkylDerivativesasSubstrate,TMEDAplaysacrucialroletoreduce-hydrideelimination,Nakamura,E.et.al.J.Am.Chem.Soc.2004,126,3686.,aPhMgBr(1.2equiv),additive(1.2equiv),30min.,.,Frstner,A.et.al.Angew.Chem.Int.Ed.2003,42,308.Frstner,A.et.al.J.Org.Chem.2004,69,3950.,SynthesisofR-(+)-MuscopyridineandimmunosuppressiveagentFTY720,.,Frstner,A.et.al.Angew.Chem.Int.Ed.2003,42,5358.,SynthesisofLatrunculinB,.,Industrialexamples,HokkoChemicalIndustry,Japan,Scale:20t/ySolvent:FromEthertoTHF,withTolueneasco-solvent.,.,.,.,Pd(PPh3)4,TON74,000910,000,环钯催化剂,PtBu3,28,000,000,ArClsubstrate,Watersoluble,.,反应底物,有机硼酸（酯）ArBr经格氏反应，或者nBuLi，与B(OR)3反应得到硼氢化反应,.,.,.,.,.,.,.,.,.,.,.,Losartan,Merck(1994),抗高血压药物JOC,1994,59,6391,.,PharmaciaCo.andDow,.,.,抗真菌剂fungizideBoscalid,BASF,1000t/y,.,Cancercellgrowthinhibitor,Novartis,.,TreatmentforHIV,.,Stille偶联,StilleCoupling,.,Substrates,Stille偶联反应中两组份的组合,.,.,锡试剂的制备,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,Hiyama偶联反应,.,F-(TBAF)activatorneeded,.,.,.,.,.,Hiyama-Denmarkcoupling,.,.,.,