Photoinduced Copper-Catalyzed Regio- and Enantioselective Alkynylation of Epoxides

Abstract

Epoxides are privileged and valuable electrophiles frequently utilized as versatile building blocks in synthetic chemistry to prepare diverse alcohols through ring-opening reactions. However, the catalytic stereoconvergent cross-coupling of racemic epoxides with electro- or nucleophiles has remained a persistent challenge. In this work, we present a mild method to achieve the regio- and enantioselective alkynylation of epoxides with various alkynes, resulting in the synthesis of β-chiral homopropargyl alcohols via a photoinduced copper-based catalytic system. The use of a monofluoro-substituted non- C 2 symmetric bisoxazoline diphenylamine ligand played a pivotal role in the success of this chemistry, with its distinct electronic and steric effects proving crucial in enhancing both reactivity and stereoselectivity. Mechanistic studies supported the idea that the reaction underwent regioselective nucleophilic ring-opening of epoxides with iodides, followed by stereoconvergent radical cross-coupling with alkynes. Notably, the hydroxyl group generated from the ring-opening of epoxide may play an auxiliary role in achieving high enantioselectivity.