Synthesis of 3-Methyleneisoindolin-1-ones via Rhodium(III)-Catalyzed C‒H/N‒H Activation and Annulation of N-Methoxybenzamides with Potassium Vinyltrifluoroborate.

Abstract

Isoindolinones are vital heterocyclic compounds in medicinal chemistry, notable for their diverse bioactivities. Significant attention has been devoted to their preparation; however, existing methods are unsuitable for constructing unsubstituted 3-methyleneisoindolin-1-ones. Herein, we present a rhodium(III)-catalyzed method for synthesizing unsubstituted 3-methyleneisoindolin-1-ones via C‒H/N‒H activation and annulation of N-methoxybenzamides with potassium (ethenyl)trifluoroborate. This approach offers mild reaction conditions, high regioselectivity, and efficient yields. Interestingly, sterically demanding or heterocyclic N-methoxyaromaticamides resulted in the formation of 2-vinyl(hetero)aromatic amides instead of 3-methyleneisoindolin-1-ones. Mechanistic insights suggest a rhodacycle intermediate pathway, highlighting the method's potential for developing new bioactive isoindolinone derivatives.