偶联反应小结.ppt

偶联反应Cross-Coupling Reaction New development of the catalyst Fe-catalyst Low initial temperature (-20 °C) is beneficial Aryl chlorides, triflates and tosylates are better substrates than aryl bromides and iodides Alkyl Derivatives as Substrate β-Hydride elimination and homocoupling are the major setback with the cross-coupling of 1o and 2o alkyl substrates with aryl Grignard reagents Alkyl Derivatives as Substrate TMEDA plays a crucial role to reduce β-hydride elimination Synthesis of R-(+)-Muscopyridine and immuno suppressive agent FTY720 Synthesis of Latrunculin B Industrial examples 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 Pfizer, CETP inhibitor CP529,411 Hiyama偶联反应 F- (TBAF) activator needed Hiyama-Denmark coupling Kosugi, 1983 Losartan, Merck (1994), 抗高血压药物 JOC, 1994, 59, 6391 Pharmacia Co. and Dow 抗真菌剂fungizide Boscalid, BASF, 1000t/y Cancer cell growth inhibitor, Novartis Treatment for HIV Stille偶联, Stille Coupling Substrates Stille偶联反应中两组份的组合 锡试剂的制备 * 经典反应式 Br, I, OTs Aryl, alkyl, vinyl Aryl Si Ni or Pd Hiyama (1988) B Sn Zn Cu Mg M Cl, Br, I, OTs Aryl, alkyl, alkynyl Aryl, alkyl Pd Suzuki (1979) Cl, Br, I, OTs Aryl, alkyl, vinyl, benzyl, allyl, acyl Aryl, vinyl,benzyl, alkynyl Pd Stille (1978) Cl, Br, I, OTs Aryl, alkyl, vinyl, alkynyl, benzyl, allyl Aryl, allyl, benzyl, propargyl Ni or Pd Negishi (1977) Br, I Aryl, alkyl, vinyl Aryl, alkyl Pd/CuI Sonogashira (1975) Cl, Br, I, OTs Aryl, alkyl, vinyl Aryl, alkyl, vinyl Ni or Pd Kumada-Corriu (1972) X R R Catalyst Cross-Coupling Reactions Kumada, Suzuki, Stille, Negishi, Hiyama coupling (C-C Formation：C-X + C-M) Buchwald-Hartwig coupling (C-N, C-O, C-S Formation: C-X + Nu (N, O, S)-H) a-Arylation of Ketone (C-C Formation: C-X + C-H) Heck, Sonogashira coupling (Alkene and alkyne Formation: C-X + C-H) General Mechanism Kumada, Kumada-Corriu Coupling 1960年Chatt和Shaw: 1970年