Density functional study on the mechanism of direct N-acylation reaction of lactams with aldehydes catalyzed by Shvo's catalyst

Abstract

Density functional theory (DFT) was used to explore the mechanism of the direct N-acylation of lactams with aldehydes under the catalysis of Shvo's catalyst. The most kinetically and thermodynamically feasible mechanism was proposed in this study. The lactam–lactim tautomerism was firstly achieved by means of a concerted intermolecular hydrogen exchange between two molecules of 2-pyrrolidinone, 1. Then, the formed lactim 2 and an aldehyde reacted to yield a hemiaminal 3via a nucleophilic reaction and a hydrogen transfer. Finally, the product 5 was generated through a dehydrogenation of the hemiaminal 3, catalyzed by ruthenium complex 4. The total Gibbs energy barrier in the catalytic cycle of N-acylation is 23.9 kcal mol⁻¹, and the generation of the hemiaminal 3 is the rate-determining step.