Divergent, Stereospecific Mono‐ and Difluoromethylation of Boronic Esters. Issue 22 (24th March 2020)

• Record Type: Journal Article
• Authors: Fasano, Valerio; Winter, Nils; Noble, Adam; Aggarwal, Varinder K.
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 22(2020)
• Page Start: 8502
• Page End: 8506
• Publication Date: 2020-03-24
• Subjects: 1, 2-migration -- boronic esters -- fluorocarbanions -- fluoromethylation -- stereospecificity; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202002246
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: There is considerable interest in incorporating fluorine into agrochemicals and pharmaceuticals to improve their biological properties. Whilst a number of methods have been reported for installing CH2 F and CHF2 groups, they are mainly limited to radical reactions, which are invariably racemic. Herein, we report the divergent, stereospecific reaction of fluoroiodomethyllithium with boronic esters to give α‐fluoro‐boronic esters. These unique intermediates can be readily transformed into the corresponding mono‐ or difluoromethylated compounds through proto‐ or fluorodeboronation, respectively. The use of the highly unstable fluoroiodomethyllithium was key to allowing rapid 1, 2‐migration over competing decomposition of the carbanion. DFT calculations informed and supported the experimental findings. Abstract : Fluoro divergence : Upon homologation of a boronic ester with fluoroiodomethyllithium, the intermediate α‐fluoro‐boronic ester can be converted into ‐CH2 F (protodeboronation) or ‐CHF2 (fluorodeboronation). The choice of the fluorocarbenoid was key, requiring a substituent that was both a good leaving group and poor at stabilizing a carbene. By exploiting the stereospecificity of the 1, 2‐migration, this approach enables complete control of asymmetry.