C[sbnd]H Bond activation of 2-isobutylthiazole at C5 position catalysed by Pd-N-heterocyclic carbene complexes

Abstract

A highly efficient and effective protocol has been developed for the synthesis of C5-(hetero)arylated 2-isobutylthiazole derivatives. Four different palladium N-heterocyclic carbene (Pd-NHCs) complexes [Pd(µ-Cl)Cl(SIMes)]2(2), (LCl2Pd-SIMes) (3: L = PPh3; 4: L = Py; 5: L = 3-CHO-Py) were synthesized and used for the first time as a catalysts in direct C-H arylation reaction of 2-isobutylthiazole at C5 position. Utilizations of these catalytic systems, the arylation of 2-isobutylthiazole with substituted (hetero)aryl bromides efficiently proceeded at low catalyst loading (1mol%) and without any additives such as PivOH under argon or aerobic conditions at 120 °C in a short time. Different substituted (hetero)aryl bromides, even some deactivated or highly sterically hindered (hetero)arylbromides, with a wide range of functional groups were successfully utilized under the optimum reaction conditions. In all cases, the C5 arylated 2-isobutylthiazoles were obtained in moderate to excellent yields.