Practical three-component synthesis of crowded arenes with donor–acceptor substitution

Abstract

An operationally simple two-step synthesis of substituted anilides has been developed. The methodology utilizes carboxamides, aldehydes, and olefins (or alkynes) as cheap starting materials and relies upon the sequential combination of condensation, cycloaddition, and oxidation reactions. The intermediate cycloadducts display various functional groups (e.g. Br, OAc, NR₂, COR, Cbz) for further chemical manipulation at the ring periphery or core. Upon oxidation with MnO₂, highly crowded anilides with up to four further substituents (alkyl, aryl, carboxylate, cyano, nitro, bromo) can be prepared in good overall yields.