Markovnikov-Selective α-C(sp3)−H Alkylation of Glycine with Alkenes via Photoredox/Co Dual Catalysis

Abstract This study reports a synergistic photoredox/cobalt catalytic strategy for the Markovnikov-selective addition of glycine derivatives to alkenes. The transformation proceeds under mild conditions, without external oxidants or stoichiometric hydrogen sources, and exhibits broad functional-group tolerance and high site-selectivity across diverse substrates, including heteroaryl motifs, pharmaceutical scaffolds, natural products, and oligopeptides. Gram-scale reactions confirm the scalability and synthetic practicality of the protocol. Mechanistic investigations reveal a dual catalytic cycle involving radical cross-coupling and identify the nitrogen-bound proton of the glycine derivative as the key hydrogen source, with α-C−H bond cleavage as the rate-determining step. This method complements our previously developed anti-Markovnikov platform, providing a concise, efficient, and controllable approach for the modular assembly and late-stage modification of α-amino acids and peptides.