A new protocol enabling the formation of trifluoromethyl compounds from acyl fluorides has been developed. 
The combination of FLUOLEAD (4-tert-butyl-2,6-dimethylphenylsulfur trifluoride) and Olah’s reagent in solvent-free conditions at 70°C initiated the significant deoxyfluorination of the acyl fluorides and resulted in the corresponding trifluoromethyl products with high yields (up to 99%). This strategy showed a great tolerance for various acyl fluorides containing aryloyl, (heteroaryl)oyl, or aliphatic acyl moieties, providing good to excellent yields of the trifluoromethyl (CF3) products. Synthetic drug-like molecules were also transformed into the corresponding trifluoromethyl compounds under the same reaction conditions. A representative reaction example is proposed below and highlighting the optimized reaction conditions to get CF3 via FLUOLEAD.
The reason why we chose the acyl-fluoride as the starting material is: (i) acyl-fluoride is thermally and hydrolytically more stable than the acyl chloride, and (ii) acyl-fluoride is readily available from the corresponding carboxylic acid as well as aldehyde and alcohol, thus the acyl-fluoride could be a good precursor for this deoxyfluorination reaction with FLUOLEAD.
The conversion of acyl fluoride to the corresponding CF3>was conducted by using FLUOLEAD and nHF-Pyridine under neat, 24h and 70°C with an extremely high yield (99%), while the reaction did not proceed without nHF-pyridine. In the second example, if we use DAST instead of FLUOLEADas deoxofluorinating agent, the reaction occurred but at a very low yield only 25%. In case that we used the other deoxyfluorination reagents such as Deoxofluor, Xtalfluor, or TBAT, the reaction did not proceed at all.Deoxyfluorination can be applied to several types of groups: Aromatics, Heterocyclic and Aliphatic.
Finally, we discovered recently a new successful work-up method based on amino-alcohol which can completely remove the side product of FLUOLEAD（Ar-SOF) and will be introduced at the conference.

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD<sup>TM</sup>/Olah’s reagent under solvent-free conditions

ACS Fall 2021

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Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEADTM/Olah’s reagent under solvent-free conditions

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^TM/Olah’s reagent under solvent-free conditions