Silver-Catalyzed (<i>Z</i>)-β-Fluoro-vinyl Iodonium Salts from Alkynes: Efficient and Selective Syntheses of <i>Z</i>-Monofluoroalkenes
Alexi T. Sedikides, Alastair J. J. Lennox
Abstract
High Resolution Image Download MS PowerPoint Slide 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.