偶联反应小结课件

1、偶联反应Cross-Coupling Reaction,1,PPT学习交流,经典反应式,2,PPT学习交流,3,PPT学习交流,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

2、 alkyne Formation: C-X + C-H),4,PPT学习交流,General Mechanism,5,PPT学习交流,Kumada, Kumada-Corriu Coupling,1960年Chatt和Shaw:,1970年Uchino等:,6,PPT学习交流,Sp3 C-X substrate?,7,PPT学习交流,8,PPT学习交流,配体的影响,9,PPT学习交流,10,PPT学习交流,格氏试剂上烷基部分的异构化,11,PPT学习交流,Fe-catalyst Low initial temperature (-20 C) is beneficial,Molander, G

3、. A. et. al. Tetrahedron Lett. 1983, 24, 5449.,New development of the catalyst,12,PPT学习交流,Aryl chlorides, triflates and tosylates are better substrates than aryl bromides and iodides,Frstner, A. et. al. Angew. Chem. Int. Ed. Engl. 2002, 41, 609.,13,PPT学习交流,-Hydride elimination and homocoupling are t

4、he major setback with the cross-coupling of 1o and 2o alkyl substrates with aryl Grignard reagents,Hayashi, T. et. al. Org. Lett. 2004, 6, 1297.,*Amount after 0.05 mmol (equivalent to catalyst) subtracted.,Alkyl Derivatives as Substrate,14,PPT学习交流,Alkyl Derivatives as Substrate,TMEDA plays a crucial

5、 role to reduce -hydride elimination,Nakamura, E. et. al. J. Am. Chem. Soc. 2004, 126, 3686.,aPhMgBr (1.2 equiv), additive (1.2 equiv), 30 min.,15,PPT学习交流,Frstner, A. et. al. Angew. Chem. Int. Ed. 2003, 42, 308. Frstner, A. et. al. J. Org.Chem. 2004, 69, 3950.,Synthesis of R-(+)-Muscopyridine and im

6、muno suppressive agent FTY720,16,PPT学习交流,Frstner, A. et. al. Angew. Chem. Int. Ed. 2003, 42, 5358.,Synthesis of Latrunculin B,17,PPT学习交流,Industrial examples,Hokko Chemical Industry, Japan,Scale: 20t/y Solvent: From Ether to THF, with Toluene as co-solvent.,18,PPT学习交流,19,PPT学习交流,Pd(PPh3)4,TON 74,000

7、910,000,环钯催化剂,PtBu3,28,000,000,ArCl substrate,Water soluble,20,PPT学习交流,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,21,PPT学习交流,22,PPT学习交流,23,PPT学习交流,24,PPT学习交流,25,PPT学习交流,26,PPT学习交流,27,PPT学习交流,28,PPT学习交流,29,PPT学习交流,Losartan, Merck (1994), 抗高血压药物 JOC, 1994, 59, 6391,30,PPT学习交流,Pharmacia Co. and

8、Dow,31,PPT学习交流,32,PPT学习交流,抗真菌剂fungizide Boscalid, BASF, 1000t/y,33,PPT学习交流,Cancer cell growth inhibitor, Novartis,34,PPT学习交流,Treatment for HIV,35,PPT学习交流,Stille偶联, Stille Coupling,36,PPT学习交流,Substrates,Stille偶联反应中两组份的组合,37,PPT学习交流,锡试剂的制备,38,PPT学习交流,39,PPT学习交流,40,PPT学习交流,41,PPT学习交流,42,PPT学习交流,43,PPT学习交流,44,PPT学习交流,45,PPT学习交流,46,PPT学习交流,47,PPT学习交流,48,PPT学习交流,49,PPT学习交流,Hiyama偶联反应,50,PPT学习交流,F- (TBAF) activator needed,51,PPT学习交流,52,PPT学习交流,Hiyama-Denmark coupling,53,PPT学习交流,54,PPT学习交流,55,PPT学习交流,Kosugi, 1983,56,PPT学习交流,57,PPT学习交流,58,PPT学习交流,59,PPT学习交流,60,PPT学习交流,61,PPT学习交流,62