Development and optimization of photoredox-mediated methine epimerization

Abstract

Reactions that edit the stereochemistry of individual atoms are enabling tools in synthetic chemistry. The Wendlandt lab has developed a sequential H-atom abstraction and donation strategy to synthesize rare sugars from biomass platform molecules such as D-glucose. Efforts to apply this strategy to the epimerization of steroids gave poor results and demonstrated limited selectivity, but insights gained from this work were used to develop a hypothesis for epimerization. We proposed that H-atom abstraction and donation occur to release diaxial strain and form the most conformationally stable isomer. This hypothesis guided the development of an epimerization method for methine stereocenters. This work describes the optimization and development of methine epimerization of isomenthyl acetate. The epimerization of tertiary alkyl stereocenters is also applied to access an otherwise synthetically challenging stereochemical outcome from a Diels-Alder reaction sequence. Data from primary literature and mechanistic experiments are used to provide a proposed mechanism through which this epimerization proceeds.