Water-Mediated Organocatalytic Formal [6 + 1] Cycloaddition via Redox-Neutral Triple sp3 C–H Alkylation: Green Access to Azepinoindole-Linked Indolenines

A water-mediated organocatalytic formal [6 + 1] cycloaddition of 2-methyl indolenines with dielectrophilic 4-amino-indole-3-carbaldehydes has been achieved through redox-neutral triple sp3 C–H alkylation. A series of azepinoindole-linked indolenines were synthesized in good yields with excellent diastereoselectivities (up to 94% yield, >20:1 dr). This method has notable features such as water as the green reaction medium, metal-free and redox-neutral conditions, atom economy, broad substrate scope, late-stage modification of drug molecules, and gram-scale synthesis.