Theoretical Investigation on Spiro-cyclisation of Maleimide and Sulfonamide Catalyzed by Pd(II) via Activated γ-C(sp3)−H to Spiro Pyrrolidine

Abstract

Abstract: Our DFT calculation provided the first theoretical investigation on Pd(OAc)2-catalyzed spiro cyclisation of sulfonamide with maleimide. Initially, Pd(OAc)2 is coordinated with quinoline leading to first N-Pd bond. Subsequently, via coordination of sulfonamide to Pd, the second N-Pd bond is generated after liberation of first acetic acid AcOH. Then C-Pd bond is formed by activation of γ-C(sp3)−H bond during formation of key five-membered ring intermediate together with leaving of second AcOH. Further coordination with maleimide to Pd affords tensioned ternary ring, which converts into expanded seven-membered palladacycle through 1,2-migratory insertion. The β-hydride elimination and resulting coordination shift undergoes yielding six-membered ring. The final reductive elimination of it generates desired five-membered spiro pyrrolidine product and recovered Pd catalyst. Comparatively, the reductive elimination is speculated as rate-limiting for Pd(II)-mediated spiro-cyclisation of sulfonamide with maleimide producing spiro pyrrolidine.

Keywords: Pd(0)/Pd(II); Spirocyclization; Diastereomer; γ-C(sp3)−H Activation; Quinoline Ligand

Citation

Nan Lu. Theoretical Investigation on Spiro-cyclisation of Maleimide and Sulfonamide Catalyzed by Pd(II) via Activated γ-C(sp3)−H to Spiro Pyrrolidine. WebLog J Mol Cell Biol. wjmcb.2025.g1502. https://doi.org/10.5281/zenodo.16148551