Palladium-catalysed regio- and stereo-controlled C-2 β-fluorovinylation of indoles

TL;DR

This paper introduces a new method to create fluorinated compounds at specific positions in indoles, which could be useful in drug development.

Contribution

A novel palladium-catalyzed method for regio- and stereo-controlled C-2 β-fluorovinylation of indoles is presented.

Findings

Z-β-fluorovinyl iodonium salts are formed from alkynes via a silver-catalyzed process.

The method achieves a broad scope of β-fluorovinyl heterocycles in good to excellent yields.

Mechanistic studies and product derivatisations support the proposed method.

Abstract

Vinyl-fluorides appended to heterocycles are a broadly underdeveloped family of functionality with potential application in bioactive compounds. Herein, we disclose a C–H functionalisation strategy for the regio- and stereo-controlled synthesis of Z-β-fluorovinyl indoles exclusively in the C-2 position. 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.

Vinyl-fluorides appended to heterocycles are a broadly underdeveloped family of functionality with potential application in bioactive compounds.

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