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 CH2F 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.

Divergent, Stereospecific Mono- and Difluoromethylation of Boronic Esters / V. Fasano, N. Winter, A. Noble, V.K. Aggarwal. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - 59:22(2020 May 25), pp. 8502-8506. [10.1002/anie.202002246]

Divergent, Stereospecific Mono- and Difluoromethylation of Boronic Esters

V. Fasano
Co-primo
;
2020

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 CH2F 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.
1,2-migration; boronic esters; fluorocarbanions; fluoromethylation; stereospecificity
Settore CHIM/06 - Chimica Organica
25-mag-2020
28-feb-2020
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/952282
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