Isolation and Characterization of Regioisomers of Pyrazole-Based Palladacycles and Their Use in α-Alkylation of Ketones Using Alcohols

5 years ago

Isolation and Characterization of Regioisomers of Pyrazole-Based Palladacycles and Their Use in α-Alkylation of Ketones Using Alcohols

Nishant Sharma, Upakarasamy Lourderaj, Shaikh Samser, Ramesh Mamidala, Krishnan Venkatasubbaiah

Regioisomers of 3,5-diphenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole-based palladacycles (1 and 2) were synthesized by the aromatic C–H bond activation of N/3-aryl ring. The application of these regioisomers as catalysts to enable the formation of α-alkylated ketones or quinolines with alcohols using a hydrogen borrowing process is evaluated. Experimental results reveal that palladacycle 2 is superior over palladacycle 1 to catalyze the reaction under similar reaction conditions. The reaction mechanisms for the palladacycles 1 and 2 catalyzed α-alkylation of acetophenone were studied using density functional theoretical (DFT) methods. The DFT studies indicate that palladacycle 2 has an energy barrier lower than that of palladacycle 1 for the alkylation reaction, consistent with the better catalytic activity of palladacycle 2 seen in the experiments. The palladacycle–phosphine system was found to tolerate a wide range of functional groups and serves as an efficient protocol for the synthesis of α-alkylated products under solvent-free conditions. In addition, the synthetic protocol was successfully applied to prepare donepezil, a drug for Alzheimer’s disease, from simple starting materials.

Publisher URL: http://dx.doi.org/10.1021/acs.organomet.7b00478

DOI: 10.1021/acs.organomet.7b00478