1. Cooperativity in Asymmetric Bimetallic Catalysis 05/20/2015 Presented By Michael C. Young

2. Strategies for Bimetallic Catalysis There are numerous intramolecular and intermolecular methods to achieve bi-metallic catalysis: Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931.

3. Pioneering Work Allylation of activated methylene compounds had originally been difficult to achieve good ee with chiral phosphine ligands. Hayashi, T.; Kanehira, K.; Tsuchiya, H.; Kumada, M. Chem. Commun., 1982, 2586. i ) NaH/THF; ii) allylacetate/[(allyl)PdCl] 2 / -30 ºC 80%, 45% ee (S) 64%, 31% ee (S) 86%, 15% ee (S)

4. Improved Allylation Protocol (I) Kumada group investigated improving the ee with a new class of chiral phosphine. Hayashi, T.; Kanehira, K.; Hagihara, T.; Kumada, M. J. Org. Chem., 1988, 113.

5. Improved Allylation Protocol (II) Replacing H-bonding with metal chelation changes solvent preference as well as stereoselectivity. Sawamura, M.; Nagata, H.; Sakamoto, H.; Ito, Y. J. Am. Chem. Soc., 1992, 194, 2586.

6. Bifunctional Asymmetric Nitro Allylation Ito and coworkers hoped that they could better understand their catalyst in another transformation. Sawamura, M.; Nakayama, Y.; Tang, W.-M.; Ito, Y. J. Org. Chem., 1996, 61, 9090. BaseSolventConc.Yield (%)ee % KFMesitylene1.0 M4014 (R) KFToluene1.0 M4719 (R) KFTHF1.0 M6625 (R) KFCH 2 Cl 2 1.0 M3325 (R) RbFTHF1.0 M5029 (R) RbFCH 2 Cl 2 1.0 M5738 (R) RbFCH 2 Cl 2 0.5 M2842 (R) CsFCH 2 Cl 2 1.0 M3131 (R) BaseR-GroupAdd.Yield (%)ee % KFMeN/A4323 (R) KFEtN/A4437 (R) KFt-BuN/A9551 (R) RbFt-BuN/A9560 (R) CsFt-BuN/A9134 (R) RbFt-BuRbClO 4 9869 (R) RbFt-BuRbClO 4 *9280 (R)

7. Trost Ligand as a Bifunctional Ligand Trost, B. M.; Radinov, R. J. Am. Chem. Soc., 1997, 199, 2586.

8. Asymmetric Carbonyl Alkylation (I) Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931. Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am. Chem. Soc., 1986, 108, 6072. AldehydeZincSolventTime (h)Yield (%)ee (%) – (S) C6H5C6H5 (C 2 H 5 ) 2 ZnPhMe69798 C6H5C6H5 (C 2 H 5 ) 2 ZnHexanes-PhMe69498 C6H5C6H5 (C 2 H 5 ) 2 ZnEt 2 O-PhMe69899 C6H5C6H5 (C 2 H 5 ) 2 ZnTHF-PhMe644491 C6H5C6H5 (CH 3 ) 2 ZnPhMe705991 P-ClC 6 H 4 (C 2 H 5 ) 2 ZnPhMe128693 (E)-C 6 H 5 CHCH(C 2 H 5 ) 2 ZnPhMe68196 C 6 H 5 CH 2 CH 2 (C 2 H 5 ) 2 ZnPhMe128090 N-C 6 H 13 (C 2 H 5 ) 2 ZnPhMe248161

9. Asymmetric Carbonyl Alkylation (II) Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931. DiMauro, E. F.; Kozlowski, M. C. Org. Lett., 2001, 3, 3053.

10. Asymmetric Carbonyl Alkylation (III) Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931. Funabashi, K.; Jachmann, M.; Kanai, M.; Shibasaki, M. Angew. Chem., Int. Ed., 2003, 42, 5489.

11. Shibasaki-BINOL Chemistry Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931. Shibasaki, M.; Kanai, M.; Matsunaga, S.; Kumagai, N. Acc. Chem. Res., 2009, 42, 1117. Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem. Soc., 1992, 114, 4418. Arai, T.; Sasai, H.; Aoe, K.-I.; Okamura, K.; Date, T.; Shibasaki, M. Angew. Chem., Int. Ed., 1996, 35, 104.

12. Asymmetric Strecker-Type Reactions Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931. Masumoto, S.; Usuda, H.; Suzuki, M.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc., 2003, 125, 5634. Kanai, M.; Kato, N.; Ichikawa, E.; Shibasaki, M. Synlett, 2005, 1491. Kato, N. et al. J. Am. Chem. Soc., 2006, 128, 16438.

13. Catalytic Asymmetric Aldol Reactions Trost, B. M.; Ito, H. J. Am. Chem. Soc., 2000, 122, 12003.

14. Diol Desymmetrization Trost, B. M.; Mino, T. J. Am. Chem. Soc., 2003, 125, 2410.

15. 1,2-Alkynylation of Aldehydes Trost, B. M.; Weiss, A. H.; von Wangelin, A. J. J. Am. Chem. Soc., 2006, 128, 8.

16. Tetrametallic Catalysis Endo, K.; Ogawa, M.; Shibata, T. Angew. Chem., Int. Ed., 2010, 49, 2410.

17. Bimetallic Salen Complexes (I) Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931.Keller, F.; Rippert, A. J. Helv. Chim. Acta, 1999, 82, 125. DiMauro, E. F>; Kozlowski, M. C. Org. Lett., 2001, 3, 1641. Chen, Z.; Furutachi, M.; Kato, Y.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc., 2008, 130, 2170. Handa, S.; Gnanadesikan, V.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc., 2007, 129, 4900.

18. Bimetallic Salen Complexes (II) Handa, S.; Nagawa, K.; Sohtome, Y.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed., 2008, 47, 3230.

19. Bimetallic Catalysis for BINOL Synthesis Gao, J.; Reibenspies, J. H.; Martell, A. E. Angew. Chem., Int Ed., 2003, 42, 6008.

20. Bimetallic Hetereogeneous Catalyst Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931. Nitabaru, T.; Kumagai, N.; Shibasaki, M. Tetrahedron Lett., 2008, 49, 272. Nitabaru, T.; Nojiri, A.; Kobayashi, M.; Kumagai, N.; Shibasaki, M. J. Am. Chem. Soc., 2009, 131, 13860.

21. “Robot-like” Bimetallic Pd Catalyst Jauntze, S.; Peters, R. Angew. Chem., Int Ed., 2008, 47, 9284. Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931.

22. Separate Metal Centers Sawamura, M.; Sudoh, M.; Ito, Y. J. Am. Chem. Soc., 1996, 118, 3309.

23. Jacobsen Catalyst (I) Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931. Martìnez, L. E.; Leighton, J. L.; Carsten, D. H.; Jacobsen, E. N. J. Am. Chem. Soc., 1995, 117, 5897.

24. Jacobsen Catalyst (II) Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science, 1997, 277, 936. Nielsen, L. P. C.; Stevenson, C. P.; Jacobsen, E. N. J. Am. Chem. Soc., 2004, 126, 1360. Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931.

25. Jacobsen Catalyst (III) Sammis, G. M.; Jacobsen, E. N. J. Am. Chem. Soc., 2003, 125, 4442. Sammis, G. M.; Danjo, H.; Jacobsen, E. N. J. Am. Chem. Soc., 2004, 126, 9928.

26. Bimetallic Epoxide Fluoridation Kalow, J. A.; Doyle, A. G. J. Am. Chem. Soc., 2010, 132, 3268. Kalow, J. A.; Doyle, A. G. J. Am. Chem. Soc., 2011, 133, 16001. Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931.

27. Bridged Bimetallic Catalysts Belekon’, Y. N.; et al. J. Am. Chem. Soc., 1999, 121, 3968. Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931.

28. CO 2 Activation With Bimetallic Complexes Clegg, W.; Harrington, R. W.; North, M.; Pasquale, R. Chem. Eur. J., 2010, 16, 6828. North, M.; Quek, S. C. Z.; Pridmore, N. E.; Whitwood, A. C.; Wu, X. ACS Cat., 2015, 5, 3398.

29. Zr-Epoxide Azidination Nugent, W. A. J. Am. Chem. Soc., 1992, 114, 2768. Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931.

30. Tethered Bimetallic Catalysis Konsler, R. G.; Karl, J.; Jacobsen, E. N. J. Am. Chem. Soc, 1998, 120, 10780. The Winner!

31. Al Together Mazet, C.; Jacobsen, E. N. Angew. Chem., Int. Ed., 2008, 47, 1762.

32. Resolution/Polymerization Thomas, R. M.; et al. J. Am. Chem. Soc., 2010, 132, 16520.

33. Vanadium Oxidation of Naphthol Guo, Q.-X.; Gong, L.-Z.; et al. J. Am. Chem. Soc., 2007, 129, 13927.

34. Tethered and Bridged Ti-Salen Zhang, Z.; Wang, Z.; Zhang, R.; Ding, K. Angew. Chem., Int. Ed., 2010, 49, 6746.

35. Oligomeric/Polymeric Scaffolds Breinbauer, R.; Jacobsen, E. N. Angew. Chem., Int. Ed., 2000, 39, 3604. Annis, D. A.; Jacobsen, E. N. J. Am. Chem. Soc., 1999, 121, 4147. Rossbach, B. M.; Leopold, K.; Weberskirch, R. Angew. Chem., Int. Ed., 2006, 45, 1309. Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931.

36. Coordination Tethered/Controlled Catalyst Gianneschi, N. C.; Bertin, P. A.; Nguyen, S. T.; Mirkin, C. A>; Zakharov, L. N.; Rheingold, A. L. J. Am. Chem. Soc., 2003, 125, 10508.

37. Hydrogen Bond Tethered Catalysts Park, J.; Lang, K.; Abboud, K. A.; Hong, S. Chem.-Eur. J., 2011, 17, 2236. Park, J.; Lang, K.; Abboud, K. A.; Hong, S. J. Am. Chem. Soc., 2008, 130, 16484. Park, J. Hong, S. Chem. Soc. Rev., 2012, 41, 6931.

38. Nanocage Embedded Catalysts Yang, H.; Zhang, L.; Zhong, L.; Yang, Q.; Li, C. Angew. Chem., Int. Ed., 2007, 46, 6861.

39. Thank you for your attention! http://debbieohi.com/blather2009/?currentPage=6, Accessed 05/20/2015.

40. Question 1 Endo, K.; Ogawa, M.; Shibata, T. Angew. Chem., Int. Ed., 2010, 49, 2410. Catalyst L1 is effective in asymmetric alkylation of enones in the presence of Cu(II) and Zn(II), while L2 shows very low reactivity and enantioinduction. Provide two structures that are likely obtained in equilibrium upon treatment of L2 with Cu(II) and Zn(II) that would explain the poor selectivity (Hint, think about the solubility).

41. Question 2 Handa, S.; Nagawa, K.; Sohtome, Y.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed., 2008, 47, 3230. Shibasaki showed that a Cu:Sm complex with tetrahydroxy Salen 1 gave syn products from a nitro Mannich reaction, while most Henry reactions catalyzed prefer to give anti products. For example, the same ligand complexed with Pd and La was found to give anti products with good selectivity. Contrast the transition states to explain this difference in selectivity. Cu/Sm/1

42. Question 3 Sawamura, M.; Sudoh, M.; Ito, Y. J. Am. Chem. Soc., 1996, 118, 3309. Ito and coworkers demonstrated that a mixture of Pd(S,S)-(R,R)-TRAP and Rh(S,S)-(R,R)-TRAP gave good enantioselectivity for the asymmetric allylation of α -cyanoesters. Although the reaction did not proceed without palladium, in the presence of only Pd(S,S)-(R,R)-TRAP the reaction gave a comparable yield, albeit with no enantioselectivity. Draw the mechanism of the reaction without Rh (remember that the Pd intermediate is cationic).