Palladium-Catalysed C2 or C5 Direct Arylation of 3-Substituted Thiophenes with Aryl Bromides

Abstract

International audienceThe Pd(OAc)2/dppb system was found to be an efficient catalyst for the direct arylation of 3-substituted thiophene derivatives. The regioselectivity of the arylation strongly depends on the thiophene substituent and also on the nature of the aryl bromide. When using 3-formyl, 3-cyano, 3-methyl, 3-hydroxymethyl or 3-bromothiophene, the 2-arylated thiophenes were obtained with 76-95% regioselectivity; whereas, the arylation of 3-formylthiophene diethylacetal or 3-acetylthiophene gave the 5-arylated thiophenes with 52-90% regioselectivity. The use of congested aryl bromides favours the arylation at C5. These reactions were performed using only 0.1 mol% of catalyst. Moreover, this procedure has been found to be tolerant to a variety of functional groups on the aryl bromide such as formyl, propionyl, benzoyl, nitrile, and nitro

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

“…On the other hand, the Pd-catalysed direct arylation of 3-substituted thiophenes has attracted much less attention (Scheme 1, top) [23–31]. With such thiophene derivatives, in most cases, either C2-arylated thiophenes or mixtures of C2- and C5-arylated products have been obtained.…”