Silver-Catalyzed ( Z )-β-Fluoro-vinyl Iodonium Salts from Alkynes: Efficient and Selective Syntheses of Z -Monofluoroalkenes.

Monofluoroalkenes are stable and lipophilic amide bioisosteres used in medicinal chemistry. However, efficient and stereoselective methods for synthesizing Z -monofluoroalkenes are underdeveloped. We envisage (Z)- β-fluoro-vinyl iodonium salts ( Z -FVIs) as coupling partners for the diverse and stereoselective synthesis of Z -monofluoroalkenes. Disclosed herein is the development and application of a silver(I)-catalyzed process for accessing a broad scope of ( Z )-FVIs with exclusive Z -stereoselectivity and regioselectivity from alkynes in a single step. Experimental and computational studies provide insight into the mechanism of the catalytic cycle and the role of the silver(I) catalyst, and the reactivity of ( Z )-FVIs is explored through several stereospecific derivatizations.