Phase-transfer-shuttle generated in situ enables novel SN1-type fluorination of sulfonium ylide with hydrofluoric acid

Abstract

The development of a nucleophilic fluorination protocol using hydrofluoric acid as the fluoride source represents a long-sought goal in the field of organofluorine chemistry. We report herein the realization of such a reaction that employed alkyl-substituted sulfonium ylides as the substrates. The key to the success of the protocol was attributed to two factors: First, as a Brønsted base, the ylide was able to be protonated by HFaq, thus serving as a phase-transfer shuttle generated in situ to bring F⁻ from aqueous phase to the organic phase promoting desolvation of fluoride ion. Second, after protonation, a sulfonium salt, a good leaving group, was generated and subsequent attacked by the fluoride to afford the alkyl fluoride. Mechanistic investigation indicates that the reaction occurs via an S_N1 pathway. Because of the nature of the cationic intermediate in the reaction, two attractive rearrangement-fluorination approaches including 1,2-aryl migration fluorination and ring-expansion fluorination were disclosed.