Tetrafluoroborate Salt Fluorination for Preparing Alkyl Fluorides

Excerpt

The tetrafluoroborate ion, BF₄⁻, is often described as “inert,” “non-nucleophilic,” and a “spectator ion.” Whilst this holds true in many instances, there are in fact an ever-increasing number of synthetically-relevant examples of fluoride transfer from the BF₄⁻ ion to an electrophilic carbon atom resulting in formation of organic fluorides. Perhaps the best-recognised transformation of this type is the Balz-Schiemann reaction (production of aryl fluorides from the pyrolysis of aryldiazonium tetrafluoroborates), which was first reported 90 years ago [1]. The utility of tetrafluoroborate salts (as well as boron trifluoride) for organic fluoride synthesis was recently and comprehensively reviewed by us, including all reported examples up to the end of 2013 [2]. The present account aims to explicate to the reader the various tactics and pitfalls involved in those reactions which result in the preparation of alkyl fluorides (i.e., form a C(sp³)–F bond) in a synthetically useful manner using BF₄⁻ ions as both the only and the stoichiometric source of fluoride. Outside this caveat, it is worthwhile mentioning that a number of reactions have been reported in which BF₄⁻ ions are present alongside other potential fluoride sources, and in many instances the precise mechanistic details regarding the actual fluorination process itself are scant at best. As a historical example, Bowers and Ringold [3, 4] reported that treatment of steroidal epoxide 1 with BF₃·OEt₂ gave fluorohydrin 3 in 39% yield, whereas use of a 1:1 mixture of BF₃·OEt₂ and HBF₄·OEt₂ provided 3 in much improved 81% yield. Ally to this that Blunt et al. [5] have shown that the presence of trace amounts of HBF₄ in BF₃·OEt₂ is crucial in promoting ring-opening fluorination of steroidal epoxide 2 (closely related in structure to 1) to give fluorohydrin 4, rather than resulting in Lewis acid-catalyzed epoxide rearrangement, then both these observations indict a pivotal role for the BF₄⁻ ion in dictating the success of these fluorination reactions. It may be that a BF₄⁻ ion is in fact the active fluoride donor in both cases; many other similar examples are evident throughout the literature for rumination by the assiduous reader [6] (Scheme 1).

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