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 bi-oisosteres 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) (dobdc4− = 2,5-dioxidobenzene-1,4-dicarboxylate). Free (NH)-heteroarenes react directly with VDF via a defluorinative pathway under mild conditions, yielding terminal N-fluorovinylated products. Various complex, biologically active molecules smoothly undergo N-fluorovinylation under these conditions in much higher yields than with the gas alone. Mechanistic investigations, including deuterium incorpo-ration experiments and density functional theory calculations, suggest that this transformation represents a rare example of a concerted nucleophilic vinylic substitution (SNV) process. This protocol can be performed on 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 alkene gases, 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.