Hydrazine-mediated carbonyl–alkyne/allene reductive olefination

Cycloolefin is a privileged motif with significant implications across multiple disciplines. While cycloolefination represents the most unified disconnection strategy, the corresponding approaches are notably scarce. Here we report a hydrazine-mediated carbonyl-alkyne reductive olefination (CARO), offering a minimalist approach to structurally complex cycloolefins. This CARO protocol is also applicable to carbonyl-allene and lactol-alkyne analogues. Experimental studies and DFT calculations suggest that the CARO follows a domino mechanism involving carbonyl-hydrazine condensation, ene reaction of free hydrazone, and denitrogenative retro-ene reaction. Its synthetic potential is demonstrated by the facile preparation of several medicinally important molecules, deuterated compounds and valuable chirons. This study provides a fundamentally distinct, operationally simple and cost-effective strategy for accessing complex architectures, appealing to both organic and medicinal chemists.