Palladium-Catalysed Regio- and Stereo-Controlled C-2 β- Fluorovinylation of Indoles

Vinyl-fluorides appended to heterocycles are a broadly underdeveloped family of functionality with potential application in bioactive compounds. Herein, we disclose a cross-coupling strategy for the regio- and stereo-controlled synthesis of Z-β- fluorovinyl indoles exclusively in the C-2 position, for which there is currently no reported routes to. Z-fluorovinyl iodonium salts, which are formed from alkynes through a Ag-catalysed process, engage in a palladium-catalysed C-2 C-H functionalisation of indoles (and pyrroles) to achieve a broad scope of β-fluorovinyl heterocycles in good to excellent yields. Mechanistic studies and product derivatisations are provided.