Dual Nickel/Titanium Catalyzed Cross‐Electrophile Coupling of Thioesters with Benzylic Alcohols

Abstract This work focuses on the development of a new method for ketone synthesis via cross electrophile coupling (XEC) starting from widely available and low‐cost reagents. We demonstrate the XEC of benzylic alcohols and thioesters under reductive conditions and in the presence of trimethylsilyl chloride (TMSCl) using a dual catalytic system consisting of an air‐stable nickel pre‐catalyst and titanocene dichloride. The reaction shows a strong dependence on substituents of both substrates. It was found that an electron‐withdrawing group on the thiol moiety of thioester is necessary to reduce by‐product formation. In contrast, electron‐donating substituents are required on the benzylic alcohol for a successful XEC. Mechanistic investigations indicate that TMSCl is presumably necessary for the in situ activation of alcohol via benzyl chloride formation. This electrophile more readily forms the benzyl radical that was captured in radical trapping experiments. Additionally, the involvement of an organomanganese or a silylether species was excluded.