Structure-performance relationships for asymmetric carbenes in Pd-catalyzed chiral alcohol oxidations

COMP 111

Robert J. Nielsen, smith@wag.caltech.edu and William A Goddard III, wag@wag.caltech.edu. Materials and Process Simulation Center, California Institute of Technology, Beckman Institute (139-74), Pasadena, CA 91125
Palladium dicarboxylate complexes of N-heterocyclic carbenes are known to catalyze the aerobic oxidation of alcohols to ketones. We sought to combine the substrate scope and rate of NHC-based catalysts with the enantioselectivity demonstrated by ((-)-sparteine)PdCl2 by introducing stereocenters into carbene frameworks and computationally screening for enantioselectivity, activity and stability. First, a mechanistic study identified the geometry of the rate-limiting transition state, i.e. transfer of the beta-hydrogen of the metal-bound alkoxide to an acetate ligand. A mechanism potentially able to racemize chiral alcohols was found to lie only slightly higher in energy. Increasing the basicity of the carboxylate ligand simultaneously lowers the barrier to substrate oxidation and inhibits racemization. Finally, the ligand screen identified specific positions at which substitution affects the activation energy of substrate oxidation and the ability of the ligand to discriminate between enantiomers of 1-phenylethanol.