Enantioselective Synthesis of 2-Substituted Alcohols Using (+)-(1<i>S</i>,2<i>S</i>)-Pseudoephedrine as Chiral Auxiliary

Abstract

An improved method for the selective synthesis of enantiopure 2-substituted alcohols is described. Highly diastereoselective alkylation of pseudoephedrine-derived amides and subsequent oxidation of the hydroxyl group in the amide side chain, leads to oxoamides. These oxoamides can be purified by crystallization or preparative HPLC to obtain diastereomeric ratios of >99:1. The following reductive cleavage of the modified auxiliary allows the epimerization-free formation of enantiopure 2-substituted alcohols with up to 99.9% ee.