An Intramolecular Hydrogen Bonding-Directed Regioselective Homodouble Aldol Domino Reaction of 1,2-Diketones for the Synthesis of Polysubstituted α-Hydroxycyclopentenones

A highly efficient and selective homodouble aldol domino reaction of readily accessible 1,2-diketones has been developed for the synthesis of polysubstituted α-hydroxycyclopentenones. This transformation proceeds under mild conditions with excellent diastereoselectivity and regioselectivity. Crucially, DFT calculations and mechanistic studies reveal that an intramolecular hydrogen bonding acts as the decisive director for the regioselectivity of the second aldol step, offering a fundamental insight into the control of polycarbonyl substrate reactivity. This practical synthetic method provides a new avenue for accessing structurally diverse α-hydroxycyclopentenones.