Redox-neutral synthesis of azepane-fused spiroindolenines via Sc(OTf)3-catalyzed cascade [1,5]-hydride transfer/cyclization

Abstract

Herein, we report the first Sc(OTf)3-catalyzed redox-neutral cascade [1,5]-hydride transfer/cyclization for the efficient synthesis of azepane-fused spiroindolenines. This structurally strained seven-membered-ring scaffold has long eluded efficient access. The reaction proceeds via Knoevenagel condensation, intramolecular hydride transfer, and cyclization, delivering the target products in good to excellent yields (up to 97%). Notably, this protocol eliminates the need for substrate pre-functionalization or external oxidants. The methodology is readily scalable to the gram scale and enables diverse downstream transformations, including late-stage coupling with zidovudine. Preliminary biological evaluation indicates that selected derivatives exhibit micromolar antiproliferative activity against ovarian cancer cells, warranting further investigation as potential anticancer agents.