偶联反应小结ppt课件.ppt
99页
偶联反应 Cross Coupling Reaction 经典反应式 Cross Coupling Reactions Catalys t MRR X Kumada Corriu 1972 Ni or Pd MgAryl alkyl vinylAryl alkyl vinylCl Br I OTs Sonogashira 1975 Pd CuICuAryl alkylAryl alkyl vinylBr I Negishi 1977 Ni or Pd ZnAryl allyl benzyl propargyl Aryl alkyl vinyl alkynyl benzyl allyl Cl Br I OTs Stille 1978 PdSnAryl vinyl benzyl alkynyl Aryl alkyl vinyl benzyl allyl acyl Cl Br I OTs Suzuki 1979 PdBAryl alkylAryl alkyl alkynylCl Br I OTs Hiyama 1988 Ni or Pd SiArylAryl alkyl vinylBr I OTs 1 Kumada Suzuki Stille Negishi Hiyama coupling C C Formation C X C M 2 Buchwald Hartwig coupling C N C O C S Formation C X Nu N O S H 3 a Arylation of Ketone C C Formation C X C H 4 Heck Sonogashira coupling Alkene and alkyne Formation C X C H General Mechanism Kumada Kumada Corriu Coupling 1960年Chatt和Shaw 1970年Uchino等 Sp3 C X substrate 配体的影响 格氏试剂上烷基部分的异构化 Fe catalyst Low initial temperature 20 C is beneficial Molander G A et al Tetrahedron Lett 1983 24 5449 New development of the catalyst Aryl chlorides triflates and tosylates are better substrates than aryl bromides and iodides EntryXYield GC ab 1I2746 2Br3850 3Cl 95 4OTf 95 5OTs 95 F rstner A et al Angew Chem Int Ed Engl 2002 41 609 Hydride elimination and homocoupling are the major setback with the cross coupling of 1o and 2o alkyl substrates with aryl Grignard reagents EntrySolventProduct Yield CDEF 1THF NMP25252426 2THF27272025 3Et2O60191212 4Et2O reflux 691899 Hayashi T et al Org Lett 2004 6 1297 Amount after 0 05 mmol equivalent to catalyst subtracted Alkyl Derivatives as Substrate Alkyl Derivatives as Substrate TMEDA plays a crucial role to reduce hydride elimination EntryaAdditiveProduct Yield GC CDEAF 1None579046 2Et3N3780115 3N Methyl morpholine 872045 4DABCO2020753 5NMP153Trace794 6TMEDA71193Trace10 Nakamura E et al J Am Chem Soc 2004 126 3686 aPhMgBr 1 2 equiv additive 1 2 equiv 30 min F rstner A et al Angew Chem Int Ed 2003 42 308 F rstner A et al J Org Chem 2004 69 3950 Synthesis of R Muscopyridine and immuno suppressive agent FTY720 F rstner A et al Angew Chem Int Ed 2003 42 5358 Synthesis of Latrunculin B Industrial examples Hokko Chemical Industry Japan Scale 20t y Solvent From Ether to THF with Toluene as co solvent Pd PPh3 4 TON 74 000 910 000 环钯催化剂 PtBu3 28 000 000 ArCl substrate Water soluble 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 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 Hiyama偶联反应 F TBAF activator needed Hiyama Denmark coupling Kosugi 1983 Pfizer CETP inhibitor CP529 411 酮的a 芳基化反应 此课件下载可自行编辑修改 供参考 感谢您的支持 我们努力做得更好 。
