Dr. Thomas Poisson, Université Normandie, INSA Rouen, CNRS, Copper Mediated Difluoromethylation Reactions

Fluorinated molecules are of great interest in pharmaceutical and agrochemical research. As a result, the design of straightforward methodologies to access to these targets remains a challenge.1

Among the fluorinated motifs, our research group was interested in the introduction of the CF2CO2Et residue by means of direct C-H bond functionalization.2 Our process based on the use of inexpensive copper catalyst and the commercially available BrCF2CO2 Et, was applied to a broad range of substrates eg. glycals,3a enamides,3b furans/benzofurans3c and electron-rich aryls derivatives.3d Mechanistic studies pointed out a plausible Cu(I)/Cu(III) catalytic cycle involved in these reactions pathways.

In a second part, our effort to develop a straightforward method to introduce the CF2PO(OEt)2 group will be disclosed. Indeed, due to the importance of this phosphate bioisoster, 4 the need to develop efficient access is of prime importance in medicinal chemistry. The use of the CuCF2PO(OEt)2 reagent to introduce this motif will be depicted as well as the discovery of a Cu-salt controlled product distribution.5,6