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

Publication date: Available online 8 November 2019Source: Comptes Rendus ChimieAuthor(s): Mohamed Elhadi Benhalouche, Hai-Yun Huang, Abdellah Miloudi, Henri Doucet, Jean-François SouléAbstractThe 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.Graphical abstract

Source: Comptes Rendus Chimie - November 9, 2019 Category: Chemistry Source Type: research