Development, Scope and Mechanisms of Multicomponent Reactions of Asymmetric Electron-Deficient Alkynes with Amines and Formaldehyde

Based on the reactive behaviour of the substrates, two synthetic routes to polysubstituted pyrimidine derivatives are presented herein: 1) A catalyst-free multicomponent reaction of electron-deficient alkynes. aliphatic amines and formaldehyde and 2) Ag-I-catalyzed synthesis of pyrimidines from electron-deficient alkynes, anilines and formaldehyde by a domino reaction. Under optimized conditions, the multicomponent reactions were accomplished with high regioselectivity and excellent yields. A computational study was carried out by using the B3LYP density functional theory to elucidate the mechanisms of the catalyst-free hydroamination reaction. Calculations showed the activation free energies of aliphatic amines were lower than those of anilines. which is consistent with the experimental results.