偶联反应小结PPT课件.ppt

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 20 C isbeneficial Molander G A et al TetrahedronLett 1983 24 5449 Newdevelopmentofthecatalyst 16 Arylchlorides triflatesandtosylatesarebettersubstratesthanarylbromidesandiodides F rstner 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 F rstner A et al Angew Chem Int Ed 2003 42 308 F rstner A et al J Org Chem 2004 69 3950 SynthesisofR MuscopyridineandimmunosuppressiveagentFTY720 20 F rstner 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 2020 1 7 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Hiyama偶联反应 66 F TBAF activatorneeded 67 68 69 70 71 Hiyama Denmarkcoupling 72 73 74 Kosugi 1983 75 76 77 78 79 80 81 8