Ring-opening decarbonylative C(sp3)–C(sp3) cross-electrophile coupling of cyclic imides with unactivated alkyl chlorides

Abstract

Herein we report a nickel-mediated decarbonylative cross-electrophile coupling of N-Boc succinimides and glutarimides with unactivated alkyl chlorides. The transformation proceeds via selective endocyclic N–C(O) activation, which opens a new entry point into C(sp³)–C(sp³) cross-electrophile coupling and, through incorporation of the ring-opened imide scaffold, establishes a highly modular platform to rapidly build molecular complexity. In situ halide exchange enables the use of abundant alkyl chlorides, while broad functional group tolerance grants access to structurally diverse α- and β-substituted amides. As a result, the method provides a new retrosynthetic disconnection to aliphatic amides, exemplified by the synthesis of densely substituted carbocyclic amides and novel capsaicin precursors. The transformation further exhibits catalytic turnover under modified conditions, demonstrating the catalytic potential of this underexplored activation mode.