Chemo-, regio-, and stereoselective tetrafunctionalization of fluoroalkynes enables divergent synthesis of 5-7-membered azacycles†

Alkyne annulation has been widely used in organic synthesis for the construction of azacycles with unique structural and physicochemical properties. However, the analogous transformation of fluoroalkynes remains a challenge and has seen limited progress. Herein we report a 1,2,3,4-tetrafunctionalization of polyfluoroalkynes for the divergent construction of 5-7-membered (E)-1,2-difluorovinyl azacycles. The use of the fluorine atom as a detachable “activator” not only obviates the use of any transition metal catalysts and oxidizing reagents, but also ensures the [3–5 + 2]-annulation and defluorinative functionalization of fluoroalkynes with high chemo-, regio-, and stereoselectivities. This method exhibits a broad substrate scope, good functional group tolerance, and excellent scalability, providing a modular platform for accessing fluorinated skeletons of medicinal and biological interest. The late-stage modification of complex molecules, the multi-component 1,2-diamination of fluoroalkyne, and the synthesis of valuable organofluorides from the obtained products further highlight the real-world utility of this fluoroalkyne annulation technology.