One-pot regioselective synthesis of substituted pyrazoles and isoxazoles in PEG-400/water medium by Cu-free nano-Pd catalyzed sequential acyl Sonogashira coupling–intramolecular cyclization

Abstract

Catalyst efficacy of in situ generated Pd-nanoparticles (PdNPs) in the regioselective one-pot synthesis of 3,5-di & 3,4,5-trisubstituted pyrazoles and 3,5-disubstituted isoxazoles in environmentally benign PEG-400/H₂O medium, which involves the sequential (i) Cu-free acyl-Sonogashira coupling (ASC) and (ii) intramolecular ynone–amine cyclization under PTC conditions was described. The results of controlled experiments support the operation of two sequential catalytic cycles (ASC/cyclization) and achievement of complementary/opposite regioselectivity via ynone-bound palladium in a one-pot approach. Moreover, the in situ PdNPs recovered after the first catalytic cycle of the one-pot reaction sequence have been reused again five times successively. Besides, prior to the above studies, the efficacy of some common Pd–N-heterocyclic carbene (Pd–NHC) complexes in catalyzing the same one-pot two-step reaction sequence (Cu-free ASC/cyclization) both in water and organic solvents was also optimized. In situ generation of PdNPs from above Pd–NHCs in water was also identified, but they are not reusable due to their large size distribution.