Coordinating activation strategy for C(sp3)–H/C(sp3)–H cross-coupling to access β-aromatic α-amino acids

摘要

The past decade has witnessed significant advances in C–H bond functionalizations with the discovery of new mechanisms. Non-precious transition-metal-catalysed radical oxidative coupling for C(sp³)–H bond transformations is an appealing strategy for C–C bond formations. The radical oxidative C(sp³)–H/C(sp³)–H cross-coupling reactions of α-C(sp³)–H bonds of amines with free radicals represent a conceptual and practical challenge. We herein develop the coordinating activation strategy to illustrate the nickel-catalysed radical oxidative cross-coupling between C(sp³)–H bonds and (hetero)arylmethyl free radicals. The protocol can tolerate a rich variety of α-amino acids and (hetero)arylmethanes as well as arylmethylenes and arylmethines, affording a large library of α-tertiary and α-quaternary β-aromatic α-amino acids. This process also features low-cost metal catalyst, readily handled and easily removable coordinating group, synthetic simplicity and gram-scale production, which would enable the potential for economical production at commercial scale in the future.