Directing Group-Controlled Regioselective [4 + 3] Annulation of Indole-2-Carboxamides with MBH Carbonates toward Highly Substituted Indole-1,2-Fused Diazepanones

Abstract

A Lewis base-catalyzed [4 + 3] annulation between dinucleophilic indole-2-carboxamides and Morita–Baylis–Hillmann (MBH) carbonates was developed to access densely substituted indole-1,2-fused diazepanones. This reaction is initiated by a Lewis base-catalyzed N-allylic alkylation of the indole scaffold with MBH carbonates, followed by intramolecular Michael cyclization. Notably, the selectivity of this process is controlled by a removable o-methoxyphenyl (OMP) directing group attached to the indole-2-carboxamides. The wide scope of substrates, high regio- and stereoselectivity, and diverse transformations highlight the potential synthetic utility of this method in drug discovery.