Defluorinative Coupling of (NH)-Heteroarenes and Unactivated Vinyl Fluorides Enabled by Metal–Organic Frameworks

N-vinyl azoles are prevalent moieties in pharmaceuticals, and fluorovinyl groups are widely recognized as carbonyl bioisosteres in drug design. Thus, N-fluorovinylated heteroarenes represent highly desirable functional groups in medicinal chemistry. To streamline the development of novel N-fluorovinylation and N-pentafluoropropenylation reactions, herein we safely handle fluorinated gases, such as vinylidene fluoride (VDF) and hexafluoropropene (HFP), as solid reagents using a metal-organic framework (MOF), Mg₂(dobdc) (dobdc^4- = 2,5-dioxidobenzene-1,4-dicarboxylate). We report for the first time that free (NH)-heteroarenes─including various complex, biologically active molecules, react directly with VDF via a defluorinative pathway under mild conditions, yielding terminal N-fluorovinylated products in good to excellent yields. The use of the gas-loaded MOF leads to much higher yields than reactions with the gas alone, likely due to its dual role as both a VDF delivery vessel and a Lewis acid catalyst. Mechanistic investigations, including deuterium incorporation experiments and density functional theory calculations, suggest that this transformation represents a rare example of a concerted nucleophilic vinylic substitution (S_NV) process. This protocol can be performed on a gram scale, and the resulting N-fluorovinyl moieties can be further diversified to yield valuable motifs, such as N-fluorocyclopropyl groups. Finally, this defluorinative coupling can be generalized to other fluorinated alkenes, such as HFP. Overall, this robust defluorinative coupling offers a straightforward strategy for synthesizing diverse fluorinated heteroarenes from readily available starting materials, providing broad access to these valuable motifs for the first time.