Utilization of rationally designed small molecule chiral selectors in novel enantioselective processes

Efforts to utilize rationally designed chiral selectors in kinetic resolutions are reported herein. The primary focus is on biphasic systems carried out in the presence of a phase transfer catalyst. Along these lines, a novel two-component chiral phase transfer catalyzed process that utilizes an achiral quaternary ammonium salt in conjunction with a chiral selector to affect an enantioselective esterification reaction is described. Hydrolysis of these esters also proceeds in an enantioselective fashion, the enantiomer involved in the more stable diastereomeric complex with the selector being sequestered from hydrolysis. As the esterification and hydrolysis occur with the opposite stereochemical sense, the later reaction can be used to scavenge the minor enantiomer produced during esterification, resulting in the production of esters with very high enantioenrichment in significant yields. An initial example of using a single entity chiral selector/phase transfer catalyst is also elucidated.; In addition, phase transfer catalyzed biphasic kinetic resolutions of several racemic amides containing electron-deficient aromatic moieties are described. The method revolves around forming Meisenheimer adducts which are stabilized by quaternary ammonium salts in a nonpolar medium. When run in the presence of a chiral selector, one enantiomer is effectively shielded from reaction. The methodology is extended to enantioselective nucleophilic aromatic substitution, reactions known to proceed through the intermediacy of a Meisenheimer adduct.