Pd-catalysed direct heteroarylation of bromobenzyl acetamide derivatives:a simple access to heteroarylated benzylamine derivatives

International audienceThe palladium-catalysed direct arylation of bromobenzylacetamide derivatives using a wide variety of heteroaromatics gives a very simple access to heteroarylated benzylacetamides. 2-, 3- and 4-Bromobenzylacetamides present a very similar reactivity. In the presence of 2-subtituted furans, thiophenes, pyrroles, thia­zoles, or imidazoles a regioselective 5-arylation was observed. The reaction of benzoxazole gave the 2-arylated compounds; whereas 3,5-dimethylisoxazole gave the 4-arylated products. In most cases, the system using PdCl(C3H5)(dppb) as the catalyst, KOAc as the base, and DMAC as the solvent gave high yields of coupling products

Palladium-catalysed direct arylations of heteroaromatics using more eco-compatible solvents pentan-1-ol or 3-methylbutan-1-ol

International audienceThe palladium-catalysed direct coupling of aryl halides with heteroaromatics in greener solvents than DMF or DMAc, which are often employed for such couplings, would be a considerable advantage for both industrial application and sustainable development. We observed that a range of aryl bromides undergoe coupling via C-H bond activation/functionalisation reaction of thiazoles or imidazoles in moderate to good yields using pentan-1-ol or 3-methylbutan-1-ol as the solvents. Pentan-1-ol and 3-methylbutan-1-ol are less toxic than DMF or DMAc, moreover they are bioresources as they can be obtained by fermentation. Therefore, these reaction conditions are certainly more eco-compatible than those generally employed for such couplings

Reactivity of (poly)fluorobenzamides in palladium-catalysed direct arylations

International audienceThe influence of fluoro-substituents on secondary and tertiary benzamides on the regioselectivity of palladium-catalysed direct arylations was studied. With most (poly)fluoro-substituted tertiary benzamides, the arylations proceed very regioselectively at ortho-positions of the fluoro substituents using 1 mol% of air-stable palladium catalysts and PivOK/DMA as the reaction conditions. With the 3,5-difluoro-substituted secondary benzamides, quite regioselective arylations at C4-positions were observed. For these reactions, a variety of substituents on the aryl bromide, such as ester, propionyl, acetyl, formyl, nitro, nitrile, trifluoromethyl, chloro, fluoro or methyl, was tolerated. These results reveal that under our reaction conditions, fluoro substituents act as better directing groups than amides in the palladium-catalysed direct arylations

Palladium-catalyzed direct arylation of heteroarenes using 1-(bromophenyl)-1,2,3-triazoles as aryl source

International audienceA variety of 1-aryl-1,2,3-triazoles contg. heteroarenes at C2-, C3- or C4-positions on the aryl ring I [Ar = 2-(2-ethyl-4-methyl-1,3-thiazol-5-yl)phenyl, 3-(5-methylthiophen-2-yl)phenyl, 4-(5-formyl-1-methylpyrrol-2-yl)phenyl, etc.; R = Me, Et, Ph] was successfully prepd. via palladium-catalyzed direct arylation. These couplings were performed by employing 1 mol% of phosphine-free Pd(OAc)2 catalyst with 1-(bromophenyl)-1,2,3-triazoles II (X = 2-Br, 3-Br, 4-Br) and heteroarenes such as 2-acetylthiophene, Me 2-methylfuran-3-carboxylate, 3,5-dimethylisoxazole, etc. as coupling partners. A wide variety of heteroarenes such as thiazoles, thiophenes, furans, pyrroles or isoxazoles was tolerated

Palladium-Based Catalytic System for the Direct C3-Arylation of Furan-2-carboxamides and Thiophene-2-carboxamides

International audienceThe palladium-catalyzed direct arylation of furans or thiophenes that contained secondary carboxamides at the C2 position proceeded regioselectively at either the C3 or C5 positions, depending on the reaction conditions. The nature of the base was crucial for controlling the regioselectivity of the reaction. We had previously observed that, in the presence of potassium acetate, direct arylation at the C5 position was favored. Herein, we report that the use of cesium carbonate as the base and xylene as the solvent selectively afforded the C3-arylated furans or thiophenes. The reactivity of furan-2-carboxamides and thiophene-2-carboxamides were similar. The reaction tolerated a range of functional groups on the aryl bromide and also heteroaryl bromide substrates