组会报告 – 深圳市计算化学与药物设计重点实验室.pdf 
组会报告 – 深圳市计算化学与药物设计重点实验室.pdf
Roles of Bases in Transition-Metal Catalyzed Organic Reactions Speaker: CHENG Guijuan Nov. 29, 2013 Outline Background 1. Applications and influences of bases in transition-metal catalyzed organic reactions 2. Factors influencing the performance of bases Roles of Bases Summary 2 Background Wide applications of bases in transition-metal catalyzed organic reactions Suzuki Coupling Reaction Heck Reaction Buchwald–Hartwig amination Entry Base %yield(GC) 1 None 5 2 K2CO3 9 3 NaOAc 21 4 NEt3 37 5 K3PO4 50 6 Cs2CO3 56 Sonogashira reaction Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10. Louie, J.; Hartwig, J. F. Tetrahedron Lett 1995, 36, 3609. Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314. 3 Background Influence of bases on transition-metal catalyzed organic reactions Different bases leads to different products. Base Conversion/ % Ratio 13:14 Na2CO3 11 20:1 K2CO3 100 >99:1 Cs2CO3 25 15:1 KOAc 81 >99:1 NaOAc 41 28:1 Et3N 3 2:1 Why different bases have different performance? Roger, J.; Požgan, F.; Doucet, H. Adv. Synth. Catal. 2010, 352, 696. Campeau, L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006, 128 , 581. 4 Background Factors influencing the performance of bases basicity, solvent, solubility, ionization ability, aggregation state metal cations: size, Lewis acidity, the HSAB theory counter anions: size, the coordination ability Effects of basicity Yoo, W. J.; Capdevila, M. G.; Du, X.W.; Kobayashi, S. Org. Lett. 2012, 14, 5326. 5 Background Study of base is complex. Most of inorganic bases have poor solubility in organic solvents. Basicity varies in different solvents. What’s the role of base in transition-metal catalyzed reactions? How do bases affect the reactions? Olmstead, W. N.; Bordwell, F. G. J. Org. Chem. 1980, 45, 3299; Kuwano, R.; Utsunomiya, M.; Hartwig, J. F. J. Org. Chem. 2002, 67, 6479. 6 Roles of Bases Activate catalyst, neutralize acids Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314. 7 Roles of Bases Deprotonation---base assisted deprotonation Transition state of a carboxylate-assisted cyclopalladation as proposed by Sokolov and Reutov (1979). Gaunt, J. C.; Shaw, B. L. J. Organomet. Chem. 1975, 102, 511. Sokolov, V. I.; Troitskaya, L. L.; Reutov, O. A. J. Organomet. Chem. 1979, 182, 537. Davies, D. L.; Donald, S. M. A.; Al-Duaij, O.; Macgregor, S. A.; Pölleth, M. J. Am. Chem. Soc. 2006, 128, 4210. 8 Roles of Bases Deprotonation---base assisted deprotonation Garcia-Cuadrado, D.; de Mendoza, P.; Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc. 2007, 129 , 6880. 9 Roles of Bases Effects of cation K salts get branched products Li salts get linear products Why? Chen, J.-P.; Peng, Q.; Lei, B.-L.; Hou, X.-L.; Wu, Y.-D. J. Am. Chem. Soc. 2011, 133, 14180. 10 Roles of Bases The transmetalation reaction between CP and M-Im is favorable if the metal ion is the soft acid K+. Chen, J.-P.; Peng, Q.; Lei, B.-L.; Hou, X.-L.; Wu, Y.-D. J. Am. Chem. Soc. 2011, 133, 14180. 11 Roles of Bases Effects of cation---interact with substrate ? Base Yield [%] none 5 NaOAc 85 Mei, T.-S.; Giri, R.; Maugel, N.; Yu, J.-Q. Angew. Chem. Intern. Ed. 2008, 47, 5215. Giri, R.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 14082. 12 Summary Bases influence catalytic reaction efficiency, yield, selectivity… Factors influencing the performance of bases basicity, solvent, solubility, ionization ability, aggregation state metal cations: size, Lewis acidity, the HSAB theory counter anions: size, the coordination ability Study of base is complex and limited. Roles of base: (1) Activate catalyst, neutralize acids (2) base assisted deprotonation (3) interact with substrate 13 14