Reactivity of N-methyl-N-(polyfluorobenzyl)acetamides and N-methyl-N-(polyfluorobenzyl)benzamides in Pd-catalyzed C-H bond arylation

The influence of fluoro substituents on the aryl group of N-methyl-N-benzylacetamides and N-methyl-N-benzylbenzamides on the regioselectivity of palladium-catalyzed direct arylations was studied. With these (poly)fluoro-substituted tertiary benzamides, the arylations proceed very regioselectively at the C-H bond flanked by two fluoro substituents using 2.5 mol% of air-stable palladium catalysts and PivOK/N,N-dimethylacetamide (DMA) as the reaction conditions. For these reactions, a variety of substituents on the aryl bromide, such as ester, propionyl, acetyl, formyl, nitro, nitrile, methoxy, or methyl, was tolerated. Nitrogen-containing heteroaryl bromides were also successfully used. These results reveal that under our reaction conditions, fluoro substituents act as better directing groups than amides in palladium-catalyzed direct arylations. (C) 2019 Academie des sciences. Published by Elsevier Masson SAS.