Photochemical Desymmetrization for Stereoselective C(sp³)-H Functionalization via HAT Catalysis

ongoing

A pressing challenge in synthetic chemistry is developing sustainable methods to convert abundant feedstocks into valuable chiral products. The DESY-HAT project addresses this by pioneering new catalytic techniques, powered by visible light, to achieve stereoselective functionalization of carbon–hydrogen (C–H) bonds, the most ubiquitous moiety in organic molecules. Specifically, the project aims to access complex chiral molecules directly from readily available C–H substrates, including natural products, through enantioselective C–H functionalization via Hydrogen Atom Transfer (HAT) processes. The DESY-HAT project focuses on using HAT to selectively target C(sp³)–H bonds in symmetrical and meso substrates. The resulting desymmetrization processes will provide direct access to highly enantioenriched chiral products. This innovative approach, combining HAT with enantioselective organocatalysis, is a largely unexplored frontier in the field. The project will develop HAT desymmetrization strategies and apply them for enantioselective C(sp³)–C(sp³) and C(sp³)–heteroatom bond formation. The project benefits from the Melchiorre group’s expertise in radical photochemistry and organocatalysis and will receive industrial guidance from Bayer AG Pharmaceuticals to identify suitable C–H substrates and assist with scaling up processes to practical applications. Through this interdisciplinary research, DESY-HAT will generate chiral compounds with biologically relevant frameworks, advancing the field of asymmetric synthesis while providing me with crucial skills for the next stage of my career.