Oxalyl Halide-Mediated Synthesis of Halogenated α,β-Unsaturated γ-Lactams from Amino Acid Derivatives

An oxalyl halide-mediated conversion of amino acid derivatives to halogenated α,β-unsaturated γ-lactams is reported. The metal-free transformation provides functionalized γ-lactams from readily available amino acid derivatives. Variation of the amine substituent, oxalyl halide, amino acid side chain, and external nucleophile enables independent diversification at N1, C3, C4, and C5, respectively. Mechanistic studies support an activation-cyclization-halogenation sequence involving multiple modes of oxalyl halide reactivity.