Enantioselective Reductive Alkenylation of α‐CF 2 H (‐CF 3 ) Amino Halides: Rapid Access to Chiral α‐CF 2 H (‐CF 3 ) Allylamines

ABSTRACT The incorporation of fluoroalkyl groups into drug candidates has garnered increasing attention in the pharmaceutical industry due to their ability to modulate lipophilicity, permeability, metabolic stability, and binding affinity. Despite significant advances realized, the means to introducing fluoroalkyl groups such as ─CF 2 H or ─CF 3 in an enantioselective manner remain scarce. Herein, we report a Ni‐catalyzed enantioselective reductive alkenylation of α‐CF 2 H or ─CF 3 amino chlorides with vinyl iodides. This method provides an efficient and modular technique for constructing stereocenters bearing a fluoroalkyl group. A key to success was the incorporation of an arylamide moiety with the substrates, which stabilizes the α‐fluoroalkyl radical intermediate, thus offering a de novo approach to access enantioenriched α‐CF 2 H (─CF 3 ) allylamines. Our protocol is characterized by its mild reaction conditions, broad substrate scope, as well as excellent enantio—and chemo‐selectivity, even in the context of late‐stage functionalization.