Difluoroacetate Derivative for the Synthesis of Difluoromethylaryls

Ethyl 2,2-difluoro-2-(trimethylsilyl)acetate (1) is utilized to introduce a difluoromethyl group in aromatic ring compounds. In the presence of copper(I) iodide and cesium fluoride, (hetero)aryl halides react with 1 to give 2-aryldifluoromethylacetate esters 2a and 2b. Both 2a and 2b can be subsequently converted into difluoromethyl aryl compounds via hydrolysis and decarboxylation.¹⁾ Furthermore, pyridine derivative 2b affords corresponding difluoromethyl compounds in a single operation upon treatment with potassium fluoride in water.²⁾ Difluoromethyl group has a high lipophilicity and an electro-withdrawing power, and also behaves as a hydrogen bond donor, so it is focused on the researches of pharmaceuticals and agrochemicals. As a result, 1 is anticipated as a promising compound for the introduction of difluoromethyl group.