Theoretical Investigation on NiF2 /Picolinic Acid-Catalyzed Chemoselective Coupling−Cyclization of 2‑Iodobenzamide and Malonate to Furnish Homophthalimide

Abstract

The first theoretical investigation on NiF2 /picolinic acid-catalyzed chemoselective cou-pling− cyclization of 2-iodobenzamide and malonate was provided by our DFT calculation. First in Ni(I)/ Ni(III) catalytic cycle, NiF2 and PicA are converted to L2 Ni(II) complex together with leaving of first HF molecule. Then malonate anion is generated from dimethyl malonate after removal of second HF molecule. The deprotona-tion of malonate gives enolate as single-electron reductant furnishing Ni(I) catalyst in concert modes. Next Ni(I) complex is coordinated with 2-iodobenzamide and undergoes oxidative addition providing aryl−Ni(III) intermediate. Subsequently, via trans metalation with malonate anion replacing iodine, another Ni(III) species is produced bearing aryl and malonyl ligands. Reductive elimination delivered ortho-acylated benzamide intermediate and regenerated Ni(I) catalyst. Finally, homophthalimide product is yielded via intramolecular nucleophilic acyl substitution. That is base-promoted cyclization followed by methanol elimination which is also determined to be rate-limiting.

Keywords: NiF2; Picolinic Acid; Cyclization; Benzamide; Homophthalimide

Citation

Nan Lu. Theoretical Investigation on NiF2 /Picolinic Acid-Catalyzed Chemoselective Coupling−Cyclization of 2-Iodobenzamide and Malonate to Furnish Homophthalimide. WebLog J Mol Cell Biol. wjmcb.2026.i1001. https://doi.org/10.5281/zenodo.22848045