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

Abstract

Here we present a [3+2] cycloaddition of rationally designed trisubstituted cyclic α‐chloroamides, primarily those incorporating pharmacological pyrazolone cores, as potent synthons for synthesizing valuable spirocyclic γ‐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 γ‐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 α‐haloamide‐mediated reactions.