FLUORINATION
In the second , with a ketone ( nonenol form ), only Fluolead can provide the geminal difluoro-compounds with 92 % yield at 70 ° C . In the case of carboxylic acid , it can convert to the corresponding bis-CF 3 compounds in neat conditions without nHF-Py at 100 ° C , with a yield of 95 %. Thanks to its good thermal stability , Fluolead can tolerate temperatures of up to 100 ° C and can carry out difficult reactions that other deoxyfluorinating reagents have never yet
Figure 2 – Comparison of deoxyfluorinating reagents
achieved . There is another type of molecule ( the ester group ), where Fluolead can be used to protect the carbonyl group as it does not react with this one .
New protocol
A new protocol has been developed , enabling the formation of trifluoromethyl compounds from acyl fluorides . A combination of Fluolead and Olah ’ s reagent in solvent-free conditions , with nHF-Py at 70 ° C
initiated significant deoxyfluorination of the acyl fluorides and resulted in the corresponding trifluoromethyl products with high yields ( up to 99 %).
Professor Norio Shibata and coresearchers at Nagoya Institute of Technology chose acyl fluoride as the starting material for two main reasons : it is more thermally and hydrolytically stable than acyl chloride ; and it is readily available from the corresponding carboxylic acid , as well as the aldehyde and the alcohol , making it potentially a good precursor for this deoxyfluorination reaction with Fluolead . 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 CF 3 products . Synthetic drug-like molecules were also transformed into the corresponding CF 3 compounds under the same reaction conditions . Figure 4 shows a representative reaction example , highlighting the optimised reaction conditions . The conversion was conducted using Fluolead and neat nHF-Py for 24 hours at 70 ° C . This led to an extremely ‣
Figure 3 – Applications of Fluolead
JUL / AUG 2021 SPECCHEMONLINE . COM
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