From Alkylarenes to α-Amino Acid Derivatives via C-Difunctionalization

Nitrogenation of the carbon-carbon bond is a powerful synthetic strategy for efficiently incorporating the N atom into substrates, showcasing the remarkable step and atom economy in molecular editing processes. However, due to the inherent challenges of cleaving inert C-C bonds, current strategies are restricted to C-monofunctionalization. Herein we report a novel C-difunctionalization strategy of alkylarenes via C-C bond cleavage, providing a unique pathway for the synthesis of unnatural amino acids. This chemistry is a promising strategy for exploring uncharted areas in C-C bond amination, moving beyond traditional C-monofunctionalization to higher-order and gain-of-function-based C-multifunctionalization. The success of this C-difunctionalization approach hinges on an entropy-driven remodeling strategy for skeleton restructuring and precisely controlled chemoselectivity for stepwise carbon editing. This operationally simple reaction provides new avenues for high-value upgrading of petrochemical feedstocks, late-stage modification of complex scaffolds, and abbreviated synthesis of bioactive molecules.