Buchwald- Hartwig Cross Coupling Reaction

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

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.

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.

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

5. Synthesis of the aromatic amine of history 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.

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

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

8. Chelating phosphane ligands Base Common inorganic base: t-BuONa, t-BuOK, NaOCH3, K2CO3, K3PO4, NaOH, LHMDS, Cs2CO3. 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 phosphaneligands. ex. K2CO3. L. S. Buchwald et al., Tetrahedron lett.,1997, 38, 6359. L. S. Buchwald et al., Tetrahedron,1996, 52, 7525.

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

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

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

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

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

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