Asymmetric alkylation with salen catalysts containing Lewis acid and Lewis base moieties

ORGN 90

Michael W. Fennie, Erin F. DiMauro, Venkatachalam Annamalai, Erin M. O'Brien, and Marisa Kozlowski. Department of Chemistry, University of Pennsylvania, 231 S 34th St, Philadelphia, PA 19104
Metal complexes of C2-symmetric bifunctional Lewis acid/ Lewis base salen ligands provide an excellent example of ligand accelerated catalysis in the enantioselective diethylzinc addition to aldehydes (up to 92% ee), and in the addition of diethylzinc to alpha-ketoesters (up to 88% ee). alpha-Ketoesters alone serve as their own ligands to promote racemic 1,2-addition of diethylzinc. In such instances, beta-hydride reduction of the carbonyl via a metalloene pathway is often the major product. Simple Lewis acid catalysis does not accelerate enantioselective 1,2-addition over these two competing pathways. Bifunctional salen catalysts, however, rapidly provide enantioenriched 1,2-addition products in excellent yield and with complete chemoselectivity. Results for the asymmetric alpha-ketoester additions detailing the scope, mechanism, and utility in pharmaceutical agent synthesis will be presented. Applications of these bifunctional salen catalysts to other transformations will also be discussed.