A 2,2‐Difluoroimidazolidine Derivative for Deoxyfluorination Reactions: Mechanistic Insights by Experimental and Computational Studies

Abstract

A N‐heterocyclic deoxyfluorinating agent SIMesF2 was synthesized by nucleophilic fluorination of N,N‐1,3‐dimesityl‐2‐chloroimidazolidinium chloride (3) at room temperature. SIMesF2 was applied to deoxyfluorinate carboxylic acids and alcohols and convert benzaldehyde into difluorotoluene. Mechanistic studies by NMR spectroscopy suggest reaction pathways of the carboxylic acid to acyl fluoride via outer‐sphere fluorinations at an imidazolidinium ion by polyfluoride. DFT studies give further insight by exploring mechanistic details which distinguish the fluorination of aldehydes from that of carboxylic acids. Furthermore, a consecutive reaction sequence for the oxidation of an aldehyde followed by in situ fluorination the generated carboxylic acid was developed.

Activation of SF5CF3 by the N-Heterocyclic Carbene SIMes

“…Heating a 1:1 mixture of SIMes and SF 5 CF 3 at 90 °C for 190 min in toluene- d 8 led to the formation of 1,3-dimesityl-2-fluoro-2-trifluoromethylimidazolidine ( 1 ), SIMesF 2 ( 2 ) and 1,3-dimesitylimidazolidine-2-sulfide ( 3 ), with NMR yields of 18%, 31%, and 31% based on the amount of SF 5 CF 3 ( Scheme 1 ). The 19 F NMR spectrum ( Figure 1 ) of the mixture shows a signal at δ = −55.8 ppm for SIMesF 2 ( 2 ), which is consistent with the literature [ 15 , 28 , 29 ], as well as a doublet at δ = −76.3 with a coupling constant 3 J FF of 4.2 Hz, and a quartet at δ = −83.1 with a coupling constant 3 J FF of 4.4 Hz for compound 1 . The formation of 3 was further confirmed through comparing the 1 H NMR spectrum with the data reported in the literature [ 15 ].…”