Catalytic reductive ring opening of epoxides enabled by zirconocene and photoredox catalysis

Aida, K.; Hirao, M.; Funabashi, A.; Sugimura, N.; Ota, E.; Yamaguchi, J.
Chem. 2022, in Press.
DOI: 10.1016/j.chempr.2022.04.010

Epoxides are key structural motifs commonly found in natural products and medicinal and agrochemical agents as well as various intermediates. Although epoxides generally act as an electrophile, reductive ring opening furnishes a nucleophilic carbon radical to undergo a variety of functionalizations. Titanocene(III) has been recognized as a unique catalysis for the reductive opening by synthetic chemists over the past 30 years. Despite the tremendous advances in the titanocene-mediated ring opening, the zirconocene counterpart is currently unknown. Intrigued by the comparatively oxophilic nature of zirconium altering the reaction profile, we investigated zirconocene-mediated ring opening. Contrasting regioselectivity renders our protocol complementary to methods with titanocene. We believe that this method will become a strategically important transformation in chemical synthesis, leading to revisiting the potential of zirconocene chemistry.