Nickel-Catalyzed Defluorinative Asymmetric Cyclization of Fluoroalkyl-Substituted 1,6-Enynes for the Synthesis of Seletracetam.

The introduction of fluorine-containing groups into organic molecules can significantly affect their physical and chemical properties and has long been used as an effective strategy for drug discovery and development. Consequently, the development of catalytic asymmetric methods for the synthesis of fluorine-containing heterocycles is highly desirable and sought after. Herein, we describe a nickel-catalyzed defluorinative asymmetric cyclization of fluoroalkyl-substituted 1,6-enynes, providing an expedient access to synthetically attractive 4-fluorovinyl-substituted 2-pyrrolidones in good yields with remarkable high levels of chemo-, regio-, and enantioselectivities (90-99 % ee,>35 examples). This protocol features readily available starting materials and excellent functional group compatibility, and exhibits complementary regioselectivity. The utility of this strategy was demonstrated in the enantioselective synthesis of the antiepileptic drug Seletracetam.