Electrochemical C(sp3)–H Fluorination

Abstract

A simple and robust method for electrochemical alkyl C–H fluorination is presented. Using a simple nitrate additive, a widely available fluorine source (Selectfluor), and carbon-based electrodes, a wide variety of activated and unactivated C–H bonds are converted into their C–F congeners. The scalability of the reaction is also demonstrated with a 100 gram preparation of fluorovaline.

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

“…In both reports, the C2/C3 selectivity for the photochemical monofluorination of (+)sclareolide was identical, suggesting a similar mechanism behind the HAT and FAT processes. This parallels the C2/C3 selectivity for the electrochemical fluorination of (+)-sclareolide, proposed to involve a Selectfluor ® radical cation [204].…”

Making electrochemistry easily accessible to the synthetic chemist

“…Additives, or the use of alternating polarity can overcome these issues. 29 How to clean the electrodes?. Electrode cleaning can have a major effect on reproducibility and different materials should be treated differently.…”

“…The advantages of the setup employed will be discussed for each type of reaction. See the following reviews for specific transformations: cross coupling, [24][25][26] CH activation, [27][28][29][30][31][32][33][34][35][36] asymmetric synthesis, 14 heterocycle formation, [37][38][39] arylation, 40 fluorination, 41 organometallic catalysis, 42,43 cation pool method. 44 The different types of reactions can be summarised as: (1) direct electrochemical reaction with solvent degradation as counter reaction, (2) direct electrochemical reaction with nonsolvent degradation as counter reaction, (3) mediated or catalysed electrochemical reaction, (4) redox combined electrochemical reaction (Fig.…”

“…This tutorial review provides an introduction to electrochemistry and is not designed to be an extensive review of all synthetic electrochemical examples. For further information recent reviews and the references therein are recommended: certain transformations including cross coupling, [24][25][26] CH activation, [27][28][29][30][31][32][33][34][35][36] asymmetric synthesis, 14 heterocycle formation, [37][38][39] arylation, 40 fluorination, 41 organometallic catalysis, 42,43 cation pool method, 44 continuous reactor types, [45][46][47][48][49][50][51][52][53][54][55] analytical tools 56,57 and general reviews and perspectives. [1][2][3][4][5][6][7][8][9][10][11][12][13]…”

Iodine Catalysis for C(sp3)–H Fluorination with a Nucleophilic Fluorine Source

“…[8] Recently, electrochemistry was also applied for direct C(sp 3 ) À H fluorination via carboncentered radical intermediates. [9] The selectivity in such methods is governed by the bond dissociation energy (BDE) of the targeted C(sp 3 )ÀH bond. Thus, discrimination problems may be encountered when multiple equivalent C À H positions are available on the same molecule.…”