偶联反应小结PPT演示课件

偶联反应Cross-CouplingReaction,1,经典反应式,2,3,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),4,GeneralMechanism,5,Kumada,Kumada-CorriuCoupling,1960年Chatt和Shaw:,1970年Uchino等:,6,Sp3C-Xsubstrate?,7,8,配体的影响,9,10,格氏试剂上烷基部分的异构化,11,12,13,14,15,Fe-catalystLowinitialtemperature(-20C)isbeneficial,Molander,G.A.et.al.TetrahedronLett.1983,24,5449.,Newdevelopmentofthecatalyst,16,Arylchlorides,triflatesandtosylatesarebettersubstratesthanarylbromidesandiodides,Frstner,A.et.al.Angew.Chem.Int.Ed.Engl.2002,41,609.,17,-Hydrideeliminationandhomocouplingarethemajorsetbackwiththecross-couplingof1oand2oalkylsubstrateswitharylGrignardreagents,Hayashi,T.et.al.Org.Lett.2004,6,1297.,*Amountafter0.05mmol(equivalenttocatalyst)subtracted.,AlkylDerivativesasSubstrate,18,AlkylDerivativesasSubstrate,TMEDAplaysacrucialroletoreduce-hydrideelimination,Nakamura,E.et.al.J.Am.Chem.Soc.2004,126,3686.,aPhMgBr(1.2equiv),additive(1.2equiv),30min.,19,Frstner,A.et.al.Angew.Chem.Int.Ed.2003,42,308.Frstner,A.et.al.J.Org.Chem.2004,69,3950.,SynthesisofR-(+)-MuscopyridineandimmunosuppressiveagentFTY720,20,Frstner,A.et.al.Angew.Chem.Int.Ed.2003,42,5358.,SynthesisofLatrunculinB,21,Industrialexamples,HokkoChemicalIndustry,Japan,Scale:20t/ySolvent:FromEthertoTHF,withTolueneasco-solvent.,22,23,24,Pd(PPh3)4,TON74,000910,000,环钯催化剂,PtBu3,28,000,000,ArClsubstrate,Watersoluble,25,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,26,27,28,29,30,31,32,33,34,35,36,Losartan,Merck(1994),抗高血压药物JOC,1994,59,6391,37,PharmaciaCo.andDow,38,39,抗真菌剂fungizideBoscalid,BASF,1000t/y,40,Cancercellgrowthinhibitor,Novartis,41,TreatmentforHIV,42,Stille偶联,StilleCoupling,43,Substrates,Stille偶联反应中两组份的组合,44,45,锡试剂的制备,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,Hiyama偶联反应,65,F-(TBAF)activatorneeded,66,67,68,69,70,Hiyama-Denmarkcoupling,71,72,73,Kosugi,1983,74,75,76,7