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.