1. Noyori Catalytic Asymmetric Hydrogenation Wang jiahao Jiahao.w@sjtu.edu.cn

2. Description Pharmaceuticals Agrochemicals Flavors Other fine chemicals

3. President, RIKEN & University Professor, Nagoya University Birth: Kobe, Japan; 1938. Education: Bachelor: Kyoto University (Professor K. Sisido), 1961. Master: Kyoto University (Professor K. Sisido), 1963. Ph.D.: Kyoto University (Professor H. Nozaki), 1967. Postdoctoral Fellow: Harvard University (Professor E. J. Corey), 1969–1970. Publications: Over 500 (original papers, reviews, chapters, commentaries, and monographs). ISI citations, ca. 35,000; h-index, 101. Patents: Over 250.

4. Historical Perspective Mechanism Variations and Improvements Synthetic utility

5. Historical Perspective Knowles, W. S.; Sabacky, M. J. Chem. Commun. 1968, 1445-1446. Horner, L.; Siegel, H.; BUthe, H. Angew. Chem. Int. Ed. Engl. 1968, 7, 942. Dang, T. P.; Kagan, H. B. J. Chem. Soc. Chem. Commun. 1971, 481. 3-15% ee 72% ee DIOP

6. Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. J. Chem. Soc. Chem. Commun. 1972, 10-11. Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman, G. L. Weinkauff, D. J. J. Am. Chem. Soc. 1977, 99, 5946-5952.

7. Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. J. Chem. Soc. Chem. Commun. 1972, 10-11. Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman, G. L. Weinkauff, D. J. J. Am. Chem. Soc. 1977, 99, 5946-5952. Monsanto L-DOPA process. S/C=20000:1

8. Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. J. Chem. Soc. Chem. Commun. 1972, 10-11. Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman, G. L. Weinkauff, D. J. J. Am. Chem. Soc. 1977, 99, 5946-5952.

9. Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. J. Chem. Soc. Chem. Commun. 1972, 10-11. Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman, G. L. Weinkauff, D. J. J. Am. Chem. Soc. 1977, 99, 5946-5952.

11. Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932-7934.

12. Synthesis of BINAP 1980 Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932–7934. Shimizu, Hideo; Nagasaki, Izuru; Matsumura, Kazuhiko; Sayo, Noboru; Saito, Takao. Acc. Chem. Res. 2007, 40, 1385–1393.

13. Synthesis of BINAP 1986 Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629–635. Shimizu, Hideo; Nagasaki, Izuru; Matsumura, Kazuhiko; Sayo, Noboru; Saito, Takao. Acc. Chem. Res. 2007, 40, 1385–1393.

14. Sayo, N.; Zhang, X.; Ohmoto, T.; Yoshida, A.; Yokozawa, T. Eur. Patent 0,771,812, 1997. Shimizu, Hideo; Nagasaki, Izuru; Matsumura, Kazuhiko; Sayo, Noboru; Saito, Takao. Acc. Chem. Res. 2007, 40, 1385–1393. Synthesis of BINAP 1997

15. Burk, M. J. Acc. Chem. Res. 2000, 33, 363-372. van den Berg, M.; Minnaard, A. J.; Schudde, E. P.; van Esch, J.; deVries, A. H. M.; deVries, J. G.; Feringa, B. L. J. Am. Chem. Soc. 2000, 122, 11539-11540. Claver, C.; Fernandez, E.; Gillon, A,; Heslop, K.; Hyett, D. J.; Martorell, A,; Orpen, A. G.; Pringle, P. G. Chem. Commun. 2000, 961-962. Reetz, M. T.; Mehler, G. Angew. Chem. Int. Ed. 2000, 39, 3889-3890. Gridnev, 1. D.; Higashi, N.; Asakura, K.; Imamoto, T. J. Am. Chem. Soc. 2000, 122, 7183-7194. DuPhos Unsaturated dihydride mechanism Mechanism

16. Ohta, T.; Takaya, H.; Noyori, R. Inorg. Chem. 1988, 27, 566-569. Kitamura, M.; Tokunaga, M.; Noyori, R. J. Org, Chem. 1992, 57, 4053-4054. Functionalized olefins including enamides, α, β- and α, γ-unsaturated carboxylic acids, allylic and homoallylic alcohols ， as well as various functionalized ketones.

17. Kitamura, M.; Tokunaga, M.; Noyori, R. J. Org, Chem. 1992, 57, 4053-4054.

18. Kitamura, Masato; Nakatsuka, Hiroshi. Chem. Commun. 2011, 842-846. Unsaturated monohydride mechanism

19. Wiles, J. A.; Bergens, S. H.; Young, Y. G. J. Am. Chem. Soc. 1997, 119, 2940-2941. Noyori, R.; Ohkuma, T.; Kitamura, M.; Takaya, H.; Sayo, N.; Kumobayashi, H.; Akutagawa, S. J. Am. Chem. Soc. 1987, 109, 5856-5858. Mashima. K.; Kusano, K.; Ohta, T.; Noyori, R.; Takaya, H. J. Chem. Soc. Chem. Commun. 1989, 1208- 1210.

20. Variations and Improvements

21. Tang, W.; Chi, Y.; Zhang, X. Org. Lett. 2002, 4, 1695-1698.

22. Suzuki coupling Ullmann coupling (+)-DTTA=(+)-(2R,3R)-2,3-o- ditoluoyltartric acid

23. Tang, W.; Chi, Y.; Zhang, X. Org. Lett. 2002, 4, 1695-1698. S/C=100:1 S/C=2000:1

24. Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura, T.; Kumobayashi, H. Adv. Synth. Catal. 2001, 343, 264–267. Shimizu, Hideo; Nagasaki, Izuru; Matsumura, Kazuhiko; Sayo, Noboru; Saito, Takao. Acc. Chem. Res. 2007, 40, 1385–1393.

25. Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura, T.; Kumobayashi, H. Adv. Synth. Catal. 2001, 343, 264–267. Shimizu, Hideo; Nagasaki, Izuru; Matsumura, Kazuhiko; Sayo, Noboru; Saito, Takao. Acc. Chem. Res. 2007, 40, 1385–1393.

26. Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura, T.; Kumobayashi, H. Adv. Synth. Catal. 2001, 343, 264–267. Shimizu, Hideo; Nagasaki, Izuru; Matsumura, Kazuhiko; Sayo, Noboru; Saito, Takao. Acc. Chem. Res. 2007, 40, 1385–1393.

27. SEGPHOS Series Shimizu, H.; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405–5432. Shimizu, Hideo; Nagasaki, Izuru; Matsumura, Kazuhiko; Sayo, Noboru; Saito, Takao. Acc. Chem. Res. 2007, 40, 1385–1393. DTBM-SEGPHOS

28. Synthetic Utility 1. Hydrogenation of dehydroamino acid derivatives Sub= (Z)- or (E)-α-(acylamino)acrylic acids or esters Burk, M. J.; Feaster, J. E.; Nugent, W. A,; Harlow, R. L. J. Am. Chem. Soc. 1993, 115, 10125-10138. DuPhos

29. Burk, M. J.; Feaster, J. E.; Nugent, W. A,; Harlow, R. L. J. Am. Chem. Soc. 1993, 115, 10125-10138.

30. Sub= β, β - disubstituted α-dehydroamino acids or esters Burk, M. J.; Bedingfield. K. M.; Kiesman, W. F.; Allen, J. G. Tetrahedron Lett. 1999, 40, 3093-3096. (S,S)-Me-BPE

31. Burk, M. J.; Bedingfield. K. M.; Kiesman, W. F.; Allen, J. G. Tetrahedron Lett. 1999, 40, 3093-3096.

32. 2. Hydrogenation of enamides 99% ee 99.5% ee

33. 3. Hydrogenation of ( β-acylamino) acrylates BINAP, DuPhos, BICP, BDPMI and MalPHOS catalyst: (S)-XylyI-o-BINAPO-Ru, (99% ee) catalyst: (S,S,R,R)-TangPhos-Rh, (93.8% ee) Tang, W.; Zhang, X. Org. Lett. 2002, 4, 4159-4161. TangPhos Up to 99.6% ee

34. Ru-Me-DuPhos, 87.8% ee Rh-BICP, 86.9% ee Ru-BINAP, 5% ee TON=200 Tang, W.; Zhang, X. Org. Lett. 2002, 4, 4159-4161.

35. 4. Hydrogenation of enol esters Wu, S.; Wang, W.; Tang, W.; Lin, M.; Zhang, X.; Org. Lett. 2002, 4, 4495-4497.

36. TON=100

37. 5. Hydrogenation of α-β unsaturated carbonyls

38. 6. Hydrogenation of unsaturated alcohols

39. 谢谢！