Reaction profiling of visible-light-mediated [2 + 1] dearomatization vs. alkylation of electron-rich arenes with aryldiazoacetates: real-time NMR monitoring, kinetics, and computational analysis

Abstract

An in-depth mechanistic and kinetic analysis of the dearomative [2 + 1] reaction between electron-rich arenes and aryldiazoesters for the regioselective and diastereoselective synthesis of norcaradienes is reported. Profiling the reaction through LED-NMR analysis gave kinetic insights into product formation and unwanted side reactions, and the influence of the electron-density profile on cyclopropanation vs. alkylation in the key dearomative step is elucidated by theoretical analysis. Synthetic utility of the obtained meso-norcaradienes was evaluated through their desymmetrization into products with six contiguous stereogenic centres, while reactive functional groups allow for subsequent manipulation into more complex carbocycles.