Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation

Abstract

Selectivity in the catalytic functionalization of complex molecules is a major challenge in chemical synthesis. The problem is magnified when there are several possible stereochemical outcomes and when similar functional groups occur repeatedly within the same molecule. Selective polyene oxidation provides an archetypical example of this challenge. Historically, enzymatic catalysis provided the only precedents. Although nonenzymatic catalysts are now known that meet some of these challenges, a comprehensive solution has remained elusive. Here, we describe low molecular weight, peptide-based catalysts discovered through a combinatorial synthesis and screening protocol that exhibit site- and enantioselective oxidation of certain positions of various isoprenols. This diversity-based approach, which exhibits features remiscent of the directed evolution of enzymes, delivers catalysts that compare favourably to the state-of-the-art for asymmertric oxidation of these compounds. Moreover, the approach culminated in catalysts that exhibit alternate site-selectivity in comparison to previously described oxidation catalysts.