A DFT study on the mechanism of the organocatalytic synthesis of a benzoxazine-substituted indolizine derivative

作者：Mao, Xin; Wang, Sufan^*; Shang, Yongjia

来源：Journal of Molecular Modeling, 2017, 23(6): 177.

DOI：10.1007/s00894-017-3328-6

• Organocatalytic synthesis
• Indolizine
• DMAP
• Density functional theory

A series of theoretical computations were conducted via density functional theory at the B3LYP/6-31 + G(d,p) level to study the mechanism of the organocatalytic synthesis of a benzoxazine-substituted indolizine derivative. Four possible alternative pathways were considered in this work. The calculated results show that the formation of an N-ylide precursor from 4-dimethylaminopyridine (DMAP) is a key step as it provides the necessary nucleophilic centre for the subsequent H-migration and H-elimination processes. The precursor N-ylide and Schiff base isomers with the most favourable activities in the preliminary work were identified theoretically by analysing the reaction mechanism. The synthetic mechanism to obtain the indolizine derivative was found to be a two-step reaction, with the rate-determining step being the first H migration to form a transition state with a four-membered ring. The catalytic activity of DMAP in the first H-migration step in the overall synthetic process greatly reduces the reaction barrier height. The chiral selectivity of the synthesis is dominated by the spatial geometry of the Schiff base functional group.

• 出版日期2017-6
• 单位安徽师范大学