Reaction mechanism of palladium-catalyzed intramolecular cyclization/hydroamination of 1-(2-aminophenyl)-3-phenylprop-2yn-1-one, CN bond formation processes studied with DFT calculations

Abstract

DFT calculations using the B3LYP level of theory were carried out in order to determine the mechanisms of the hydromination reaction and of the cyclization reaction of 1-(2-aminophenyl)-3-phenylprop-2yn-1-one R1. Hydromination of R1 by diethylamine leads to 2-phenylquinolin-4 (1H)-one P1, while the catalytic cyclization using different palladium complexes as catalysts leads to the production of (2Z)-2-benzylidene-1,2-dihydro-3H-indol-3-one P2. Analyzing the potential energy surface indicates that the formation of the CN bond in the presence of diethylamine is related to high activation energies. In addition, the calculations show that there are two reaction paths for the palladium-catalyzed cyclization reaction of R1; the first one is of [1,6]-H shift type while the second is of [1,5]-H shift type, followed by the formation of a CN bond. In each case, this is the rate-determining step. We compare the Pd complexes and determine the one with the best catalytic performance in the production of P2.