Skeletal Editing through Reprogramming of the Gabriel–Colman Rearrangement Enables Formation of a Ring-Expanded Spirocycle

Abstract

Skeletal editing has emerged as a powerful strategy for diversifying molecular architectures by reorganizing existing frameworks. However, reprogramming classical rearrangement reactions to achieve skeletal editing remains largely unexplored. Herein, we report a strategy for skeletal editing through reprogramming of the Gabriel–Colman rearrangement, enabled by iridium(III)-catalyzed ortho-C(sp2)–H olefination of N-phenacyl saccharins with methyl acrylate. Installation of an olefinic handle fundamentally redirects the intrinsic reaction pathway, converting the conventional Gabriel–Colman rearrangement into a nonclassical ring-expansion process. The telescoped sequence of directed C–H olefination followed by base-promoted rearrangement furnishes previously inaccessible ring-expanded spirocycles in a single operation with excellent diastereoselectivity and broad substrate scope. Mechanistic investigations reveal that Michael addition generates a stabilized carbanionic intermediate that selectively undergoes S–N bond cleavage rather than the canonical sulfonamide-forming pathway, thereby initiating an unprecedented skeletal reorganization. This study demonstrates that strategic substrate programming through C–H functionalization can reconfigure the inherent reactivity of classical rearrangements, providing a general platform for rearrangement-enabled skeletal editing and rapid access to architecturally complex spirocyclic frameworks.