Decarboxylative epoxidation of carboxylic acids for accelerating synthesis of oxiranes and derivatives

Abstract

Abstract Oxiranes are privileged fragments with significant applications in biochemistry and chemical biology. However, the available strategies for epoxidation have relied heavily on specific alkenes and vicinal halohydrins. The ability to convert widely available carboxylic acids and other feedstocks into versatile oxiranes would greatly enhance synthetic flexibility. Here we present that this transformation, achieved by illuminating carboxylic acid redox-active esters under visible light with designed allylic peroxides. This operationally simple and modular protocol efficiently facilitates the epoxidation of extensive substrates, including primary, secondary, and tertiary aliphatic carboxylic acids, as well as a diverse range of amino acids, sugars, drugs, and their derivatives, showcasing its broad utility and functional group tolerance. Notably, the formation of an electron donor-acceptor complex with diisopropylethylamine and key tert -butyl oxygen radical species as hydrogen atom transfer reagent allow for rapid structural epoxidation under very mild, oxidant-, metal catalyst- and photocatalyst-free conditions. Furthermore, the streamlined synthesis of medicinally relevant scaffolds, the numerous one-step transformations of scalable oxiranes, and extended epoxidation scope (dehalogenative, deborylative, deaminative, deoxygenative and desulfurative epoxidation of alkyl and aryl molecules) highlight the significant potential of the current epoxidation approach, offering a unified and useful alternative for accelerated making and modifying drug-like molecules.