From alkynes to spiroindole δ-lactams via a copper-nitrenoid intermediate featuring unusual 1,1-addition and high Z-selectivity

Abstract

This study reports a novel, operationally efficient N-heterocyclic carbene (NHC)-copper-catalysed strategy for the synthesis of spiroindole δ-lactams via the coupling of dioxazolones with alkyne derivatives. The protocol demonstrates high atom economy, excellent product yields, broad functional group tolerance, and outstanding Z-stereoselectivity. Detailed mechanistic investigations, combining density functional theory (DFT) calculations with Kinetic isotope effect (KIE) experiments, reveal that the efficient formation of the copper alkyne intermediate is the key factor governing the progression of this transformation. The observed 1,1-addition of unactivated alkynes, delivering high Z/E stereoselectivity and excellent regioselectivity, is proposed to proceed via a hydrogen atom migration mechanism.