Enantioselective catalytic epoxidation of cinnamate esters

Abstract

A broad study of the (salen)Mn(III)-catalyzed asymmetric epoxidation of cis-cinnamate esters reveals that the steric properties of the ester group have a profound influence on enantioselectivity in the epoxidation reaction, with bulkier esters affording highest ee's. The sensitivity of the reaction selectivity to the steric properties of the cis-alkene are consistent with a “skewed” side-on approach of olefin to the metal-oxo. The electronic properties of the substrate arene ring substituents do not correlate with epoxidation ee, but instead with the cis/trans partitioning of product formation. Evidence is provided for a non-polar intermediate in a stepwise oxygen-atom-transfer mechanism. The presence of pyridine N-oxide derivatives has a significant effect on catalysts rates and total turnovers, but negligible influence on the stereoselectivity of epoxidation. A mechanistic basis for the role of these additives is proposed. The synthetic applicability of the cinnamate epoxidation methodology is illustrated in the highly enantioselective synthesis of diltiazem.