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

Abstract

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.