Ligand Combination Approach in Pd-Catalyzed Direct C-H Arylation of Benzothiazole and Benzoxazole

The use of ligand combination approach in the Pd catalyzed direct C-H arylation of benzothiazole and benzoxazole is demonstrated. The combination of two ligands phenanthroline monohydrate (Phen.H2O) and triphenylphosphine (PPh3) with Pd-catalyst have offered the best catalytic properties in the C-H bond arylation reactions than either of two ligands employed separately in the reactions. This protocol exhibits a wide substrate scope affording C2 arylated benzothiazole and benzoxazole derivatives in excellent yields. Mechanistic studies including kinetic isotope effect (KIE), H/D exchange and competition experiments show that the C-H bond activation of benzothiazole and benzoxazole is very facile under reaction conditions. Furthermore, different mechanistic pathways originated from the catalytically active species such as Pd(eta 2-dba)L (dba=dibenzylidene acetone) and Pd(PPh3)2 were investigated using computational methods. The computational results suggest that the generation of catalytically active species from Pd2(dba)3 is endoergic process and Phen ligand can initiate this step. On the other hand, the presence of PPh3 could be crucial for the oxidative addition of aryl halides which is the rate-determining step of the reaction. Two is better than one! A combination of two ligands (Phen.H2O and PPh3) with Pd catalyst offers a highly efficient catalytic system for the direct C-H arylation of benzothiazole and benzoxazole with aryl halides. Mechanistic studies including kinetic isotope effect experiments and computational investigations suggests that two ligands may work cooperatively to enhance the catalytic activity in the reaction.image