Attaching the Fluorine Atom to Organic Molecules Using BrF₃ and Other Reagents Directly Derived from F₂

Abstract

Elemental fluorine is a starting point for nucleophilic fluorinations (e.g., BrF3), radical fluorinations (e.g., F2 under irradiation), and electrophilic fluorinations (e.g., AcOF). All three categories are represented in this Account. Bromine trifluoride, although commercially available, can be readily made from the elements and is a very good source for naked nucleophilic fluoride ions. To minimize radical reactions, an anchor has to be installed in the molecules with which it reacts. Such an anchor is constituted of a soft base such as nitrogen and especially sulfur atoms. This reagent was used for constructing compounds with a CF2, CF3, CHF2, or CF2COOH group in specific sites. F2 itself was used for completing perfluorination of various polyfluoroethers, while the electrophilic acetyl hypofluorite is an excellent tool for introducing a single fluorine atom into organic molecules such as carboxylic acids and nitro compounds.

A new method for making acyl fluorides using BrF3

“…An additional condition is the presence of some anchor in the substrate so the reagent molecules can regroup themselves around the reacting center and release eventually their naked nucleophilic fluorine atoms. We have performed several reactions along these lines summarized in our latest account [11]. One of these reactions was the oxidation of alcohols to the corresponding acyl fluorides using BrF 3 , although in this case the formation of large amounts of by-products in the form of symmetric esters could not be avoided [12].…”

“…It seems that carboxylic acids that in general do not have a good complexing anchor for the reagent [11] and which enjoy extra stability from the carboxylate resonance, react relatively slowly (a full conversion of the starting material is achieved in a matter of seconds, but apparently it is not fast enough) allowing enough time for indiscriminate radical reactions around other regions of the molecule.…”

“…However, the reaction of the acyl chloride is much faster and it is possible to form the acyl fluoride without affecting the aliphatic C-Cl bond. This is demonstrated by reacting 5-chloropentanoyl chloride (11) with BrF 3 resulting in the new corresponding acyl fluoride 11a (Scheme 2).…”

Strategies for nucleophilic, electrophilic, and radical trifluoromethylations

“…Differently, introduction of a CF 3 group in trifluoromethylation reactions is a carbon-carbon bondforming reaction. Alternatively, trifluoromethyl unit could be constructed from various precursors: (i) from a trichloromethyl unit with the aid of anhydrous hydrogen fluoride, (ii) from a carboxy group by treatment with hydrogen fluoride and sulfur tetrafluoride, (iii) from a dithiocarboxylic acid with xenon difluoride, (iv) by oxidative desulfurisation-fluorination by means of amine-HF complexes and a source of positive halogen, (v) by use of bromine trifluoride and HOF-CH 3 CN in the synthesis of a-trifluoromethyl acids, (vi) through a difluorocarbene generated from difluorodiiodomethane or bromodifluoroacetate [5][6][7][8]. In the past few years, the field of direct trifluoromethylation has evolved rapidly to become a dynamic field that has attracted the efforts of several research groups [9].…”

Selective Reactions of Bromine Trifluoride in Organic Chemistry

“…A few of these changes have been summarized in a very concise manner more than 5 years ago. [14] We will review here most organic reactions with BrF 3 of the last 30 years or so. We will not cover the numerous reactions based on a mixture of two reagents providing electrophilic bromine and nucleophilic fluoride such as HF/NBS, sometimes marked as [BrF], and whose reactions lead occasionally to somewhat similar results.…”