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

M. Elhadi Benhalouche (1) , H.-Y. Huang (1) , A. Miloudi (2) , H. Doucet (1) , Jean-François Soulé (1)

1 ISCR - Institut des Sciences Chimiques de Rennes
2 Université d'Oran 1 Ahmed Ben Bella [Oran]

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.

Keywords: Amines; Biaryl; C–H bond functionalizations; Fluorine; Palladium

Domains: Chemical Sciences; Organic chemistry; Chemical Sciences; Catalysis

M. Elhadi Benhalouche, H.-Y. Huang, A. Miloudi, H. Doucet, Jean-François Soulé. Reactivity of N-methyl-N-(polyfluorobenzyl)acetamides and N-methyl-N-(polyfluorobenzyl)benzamides in Pd-catalyzed C–H bond arylation. Comptes Rendus. Chimie, 2019, 22 (9-10), pp.628-638. ⟨10.1016/j.crci.2019.10.001⟩. ⟨hal-02536618⟩