Cobalt-Catalyzed Chemo- and Enantioselective [4+1] Annulation toward the Synthesis of Chiral Isoindolinones: Vinyl Silanes as One-Carbon Synthons

Herein, we disclose an efficient enantioselective strategy for the synthesis of isoindolinones via cobalt/salox-catalyzed [4+1] annulation of benzamides with vinyl silanes. This transformation proceeds through sequential C−C and C−N bond formation while exploiting vinyl silanes as selective one-carbon synthons. The methodology exhibits broad substrate compatibility, accommodating diverse benzamides and vinyl silanes to deliver isoindolinone derivatives in high yields (up to 98%) with high enantioselectivity (up to >99:1 er). Furthermore, scalability studies, along with photochemical and electrochemical adaptations, highlight the practical utility and robustness of the protocol. Mechanistic insights were supported through control experiments, leading to a plausible catalytic pathway for the reaction. The synthetic utility of the method has been demonstrated through the post-synthetic diversification of the isoindolinones and late-stage functionalization reactions.