Origin of Enantioselectivity in CF_3-PIP-Catalyzed Kinetic Resolution of Secondary Benzylic Alcohols

摘要

Nonenzymatic enantioselective acyl transfer catalysis has been an active area of research for over a decade. Many of the catalysts developed to date have demonstrated varying degrees of enantioselectivity in kinetic resolution of secondary alcohols. Secondary benzylic alcohols have enjoyed particular popularity as substrates in this reaction. However, the origin of enantioselectivity in this process has not been elucidated. In this communication, we present the results of our computational studies, which support the involvement of π-interactions in the chiral recognition of this class of substrates.rnIn 2004, we introduced a new class of enantioselective acyl transfer catalysts. Among the first-generation catalysts, CF3-PIP 1 proved to be particularly effective in the kinetic resolution of secondary benzylic alcohols (2). Structure-selectivity trends observed in this initial study led us to hypothesize that the chiral recognition depends on π-π and cation-π interactions between the pyridinium ring of the N-acylated catalyst and the benzene ring of the substrate, as shown in the proposed transition state model 4 (Scheme l). Later, this hypothesis proved to be valuable as a guide in the development of subsequent generations of related catalysts. Their application to benzylic, allylic, and propargylic alcohols, 4-aryl-oxazolidinones, and 2-aryl-cyclo-alkanols produced results that were also consistent with the π-stacking mechanism.