Palladium Catalyzed Aerobic Oxidation of Alcohols: Contributions of Matthew S. Sigman and Brian M. Stoltz Jean-Nicolas Desrosiers October 30 th, 2007 Literature Meeting General Approaches for Kinetic Resolution of Alcohols Metal Catalyzed Kinetic Resolution by Derivatization Metal Catalyzed Oxidative Kinetic Resolution (OKR) Research Work of Sigman and Stoltz Outline Historical Background: Aerobic Palladium Oxidation Mechanism of the Aerobic Oxidation Role of the Molecular Sieves What comes next Sigmans Preliminary Results Optimization of the Solvent Optimization of the Temperature Optimization of the Pd Source Sigman Submitted his Work to JACS on March 15, 2001 Stoltz Submitted his Work to JACS on March 9, 2001 Improving the System with Protic Solvents Scope: Benzylic Alcohols Scope: Non-Benzylic Alcohols Scope: Desymmetrization of 1,3-meso-Diols Why an Excess of Sparteine? Achiral Exogenous Base Does the Carbonate Modify the Catalyst Structure? Oxidative Kinetic Resolution with Ambient Air Comparison of the Reaction Conditions The Mechanism Proposed Dissociative Pre-Equilibrium Rate Determining Step Kinetic Studies Which Step is Rate Determining? Rate Determining Step Kinetic Isotope Effect Hammett Studies at High Concentration of Sparteine Hammett Studies at low Concentration of Sparteine Eyring Studies Kinetic vs Thermodynamic Control Enantioselective Deprotonation Symmetry of (-)-Sparteine Model for the Enantioselective -H Selectivity vs Anion No Exogenous Base with OAc Possible Pathways for Pd Oxidation by O 2 DFT Study of Pd Oxidation Solvent Effect and Mechanism Wrap-up Application of the OKR Key Building Blocks Singulair OKR Claisen Rearrangement Retrosynthetic Analysis for Amurensinine Total Synthesis of Amurensinine Conclusions