[3+2] Cycloaddition of Rationally Designed Trisubstituted Cyclic -Chloroamide: an Alternative Strategy for Accessing Spirocyclic -Lactam Architecture

Here we present a [3+2] cycloaddition of rationally designed trisubstituted cyclic alpha-chloroamides, primarily those incorporating pharmacological pyrazolone cores, as potent synthons for synthesizing valuable spirocyclic gamma-lactam architectures. This protocol exhibits 52-96% yields, impressive substrate compatibility, and scale-up capacity. Importantly, this study also represents one of the rare examples that harness enaminone C-N bond cleavage to engineer relevant spirocyclic gamma-lactam skeletons of biological interest. Moreover, we propose a plausible mechanistic explanation to elucidate the outstanding chemical outcomes observed, thereby enriching the synthetic toolbox for pyrazolone chemistry and alpha-haloamide-mediated reactions.