1. Palladium Catalyzed Aerobic Oxidation of Alcohols: Contributions of Matthew S. Sigman and Brian M. Stoltz Jean-Nicolas Desrosiers October 30 th, 2007 Literature Meeting

2. General Approaches for Kinetic Resolution of Alcohols

3. Metal Catalyzed Kinetic Resolution by Derivatization

4. Metal Catalyzed Oxidative Kinetic Resolution (OKR)

8. Research Work of Sigman and Stoltz

9. Outline

10. Historical Background: Aerobic Palladium Oxidation

13. Mechanism of the Aerobic Oxidation

14. Role of the Molecular Sieves

15. What comes next…

16. Sigman’s Preliminary Results

17. Optimization of the Solvent

18. Optimization of the Temperature

19. Optimization of the Pd Source

20. Sigman Submitted his Work to JACS on March 15, 2001

21. Stoltz Submitted his Work to JACS on March 9, 2001

22. Improving the System with Protic Solvents

23. Scope: Benzylic Alcohols

25. Scope: Non-Benzylic Alcohols

26. Scope: Desymmetrization of 1,3-meso-Diols

27. Why an Excess of Sparteine?

29. Achiral Exogenous Base

30. Does the Carbonate Modify the Catalyst Structure?

31. Oxidative Kinetic Resolution with Ambient Air

33. Comparison of the Reaction Conditions

34. The Mechanism Proposed

35. Dissociative Pre-Equilibrium

36. Rate Determining Step

37. Kinetic Studies

38. Which Step is Rate Determining?

39. Rate Determining Step

40. Kinetic Isotope Effect

41. Hammett Studies at High Concentration of Sparteine

42. Hammett Studies at low Concentration of Sparteine

43. Eyring Studies

44. Kinetic vs Thermodynamic Control

45. Enantioselective Deprotonation

46. Symmetry of (-)-Sparteine

47. Model for the Enantioselective  -H

49. Selectivity vs Anion

50. No Exogenous Base with OAc

51. Possible Pathways for Pd Oxidation by O 2

52. DFT Study of Pd Oxidation

53. Solvent Effect and Mechanism Wrap-up

54. Application of the OKR

55. Key Building Blocks

56. Singulair

57. OKR – Claisen Rearrangement

58. Retrosynthetic Analysis for Amurensinine

59. Total Synthesis of Amurensinine

63. Conclusions