Continuous‐Flow Synthesis of Biaryls by Negishi Cross‐Coupling of Fluoro‐ and Trifluoromethyl‐Substituted (Hetero)arenes. Issue 35 (26th July 2016)

• Record Type: Journal Article
• Authors: Roesner, Stefan; Buchwald, Stephen L.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 35(2016)
• Page Start: 10463
• Page End: 10467
• Publication Date: 2016-07-26
• Subjects: biaryls -- cross-coupling -- flow chemistry -- palladium -- synthetic methods; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201605584
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A continuous‐flow method for the regioselective arylation of fluoroarenes and fluoropyridines has been developed. The telescoped procedure reported here consists of a three‐step metalation, zincation, and Negishi cross‐coupling sequence, providing efficient access to a variety of functionalized 2‐fluorobiaryl products. Precise temperature control of the metalation step, made possible by continuous‐flow technology, allowed for the efficient preparation of the arylated products in high yields and short residence times. Additionally, several examples of the regioselective arylation of benzotrifluoride derivatives are also provided. Abstract : Hey! Ho! Let's flow ! A highly regioselective functionalization of fluoro‐ and trifluoromethyl‐substituted arenes and pyridines under continuous‐flow conditions is described. This method telescopes a directed lithiation, a zincation, and a Negishi cross‐coupling into a single process to provide diversely functionalized, pharmaceutically relevant biaryls.