1. Buchwald-Hartwig Cross Coupling Reaction Reporter: Ying-Chieh CHAO Lecturer: Professor Guey-Sheng Liou Advisor: Professor Ru-Jong Jeng Data:2013/12/27 Pd-Catalyzed Amination 1

2.  Stephen L. Buchwald(1955-)  He entered Harvard University as a National Science Foundation Predoctoral Fellow in 1977 and received his Ph.D. in 1982.  In 1984 he began as an assistant professor of chemistry MIT. He was promoted to the associate professor (1989) and to Professor (1993) and was named the Camille Dreyfus Professor in 1997. 2

3.  John F. Hartwig(1964-) University of California, Berkeley  A.B. Princeton University, 1986  Ph.D. University of California, Berkeley, 1990  American Cancer Society Postdoctoral Fellow, Massachusetts Institute of Technology, 1990-1992 research focuses on the discovery and understanding of new reactions catalyzed by transition metal complexes. 3

4. Synthesis of the aromatic amine of history  Disadvantages Cumbersome step Harsh reaction conditions T. Migita et al., Chem. Lett., 1983, 927. P.E. Fanta et al., Synthesis, 1974, 9.  Disadvantages Chlorobenzene and iodobenzene can not react Water and heat sensitive 4

5. S. Buchawald et al., J. Am. Chem. Soc., 1994, 116, 7901. S. L. Buchwald et al., Angew. Chem. Int. Ed., 1995, 34, 1348. J. F. Hartwig et al., Tetrahedron lett., 1995, 36, 3609. Synthesis of the aromatic amine of history 5

6. Buchwald-Hartwig Cross Coupling Reaction 6 S. L. Buchwald et al., Angew. Chem. Int. Ed., 1995, 34, 1348. J. F. Hartwig et al., Tetrahedron lett., 1995, 36, 3609.

7. 7 Can’t castylst for chlorobenzene Mondentate ligands M. Tanaka et al. M. Tanaka Tetrachedron lett. 1997, 38, 4807. Y. Kioe Tetrahedron lett. 1998, 39, 617.  Advantages Can reacted under mild condition Reduced the amount of catalyst Reduced formation of byproducts  Disadvantages P(t-Bu) 3 is air-sensitive Electron-rich monodendate phosphine ligands S. L. Buchwald et al., Angew. Chem. Int. Ed., 1999, 38, 2413. S. L. Buchwald et al., Angew. Chem. Int. Ed., 1999, 38, 2570. S. L. Buchwald et al., J. Am. Chem. Soc., 2003, 125, 6653.  Advantages Can react at room temperature Not air-sensitive

8. 8 Chelating phosphane ligands Common inorganic base: t-BuONa, t-BuOK, NaOCH 3, K 2 CO 3, K 3 PO 4, NaOH, LHMDS, Cs 2 CO 3. Base Common organic base: DBU, MTBD. strong base is suitable Mondentate ligands and Electron-rich monodendate phosphine ligands. ex. t-BuONa. weak base is suitable Chelating phosphane ligands. ex. K 2 CO 3. L. S. Buchwald et al., Tetrahedron lett., 1997, 38, 6359. L. S. Buchwald et al., Tetrahedron, 1996, 52, 7525.

9. 9 Solvent Common solvent: toluene, xylene, THF, DME, Dioxane, DMF, NMP, DMSO. J. F. Hartwig et al., J. Org. Chem., 2002, 67, 6479. J. M. McNamara et al., Org. Lett., 2002, 4, 3481. Most of this reaction catalysts and ligands for water and oxygen sensitive.

10. 10 J. F. Hartwig et al., Org. Lett., 2008, 10, 4109-4112. 52-98%

11. 11 S. L. Buchwald et al., J. Am. Chem. Soc., 2010, 132, 15914-15917.

12. 12 J. F. Hartwig et al., J. Am. Chem. Soc., 2009, 131, 11049-11061.

13. 13 S. L. Buchwald et al., J. Am. Chem. Soc., 2008, 130, 13552-13554. Z. Zhang et al., Synlett, 2011, 955-958. S. L. Buchwald et al., J. Org. Chem., 2006, 71, 430-433. W. Song et al., Org. Lett., 2011, 13, 1784-1786.

14. water-containing solvent systems 14 Thank you for your attention!! G. Boche et al., Chem. Commun., 1998, 1509-1510. BINAS-6