Directing Group-Controlled Regioselective [4 + 3] Annulation of Indole-2-Carboxamides with MBH Carbonates toward
Shutao Wang1,2, Wenyao Zhang1, Zhuoqi Zhang1
1The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, P. R. China.
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.
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