Nickel‐Catalyzed Reductive Cross‐Coupling of α‐Trifluoromethylated Alkyl Electrophiles and Allylic Sulfones

Abstract

Fluorinated motifs are commonly found in drugs and agrochemicals. The inclusion of fluorine‐containing motifs in drug candidates during lead optimization has become a valuable strategy in pharmaceutical research and development. Significant research efforts have been dedicated to synthesizing molecules with a trifluoromethyl (CF3−) group on a stereogenic carbon. Herein, we disclose a mild and efficient nickel‐catalyzed reductive cross‐coupling between α‐trifluoromethyl alkyl bromides and allylic sulfones, enabling the efficient synthesis of α‐trifluoromethyl homoallylic alkanes. This reaction featuring base‐free, mild conditions, a broad substrate scope, and high functional group tolerance. The synthetic versatility of this approach is further underscored by its successful application in the late‐stage functionalization of a range of drug molecules. Our preliminary mechanistic study suggests that this allylation process operates through a radical intermediate.