A Computational Study on the DMAP-Catalyzed Regioselective [2+4] Cyclization of Allenic Ester with Cyclic Ketimine

【作者】 刘秋丽； 李雪； 汪洋； 魏东辉；

【Author】 Liu,Qiuli;Li,Xue;Wang,Yang;Wei,Donghui;The College of Chemistry and Molecular Engineering,Zhengzhou University;Department of Material and Chemical Engineering,Zhengzhou University of Light Industry;

【机构】 郑州大学； 郑州轻工业学院；

【摘要】 Based on the experiment,[1] the mechanism of [2 + 4] cyclization of allenic esters and cyclic ketimines catalyzed by 4-dimethylaminopyridine(DMAP) for forming highly functionalized hydropyridine derivatives has been theoretically studied using density functional theory(DFT), which had been used to study the mechanisms of organocatalytic reactions.[2-7] We have considered and studied three possible channels, including the DMAP-catalyzed [β,γ]-/[α,β]-[2 + 4] cyclization(denoted as channel A/B) and the direct [β,γ]-[2 + 4] cyclization(denoted as direct channel). According to the calculated results, channel A is revealed to be the most energetically favorable among the three channels and its generated product is the main product, which is consistent with the experimental observation. The most favorable channel A contains several steps, i.e., nucleophilic addition on the Cβ atom of allenic ester by DMAP, the stepwise [β,γ]-[2 + 4] cyclization with ketimine, and the dissociation of DMAP with product. The analyses of the global reactivity index(GRI) and frontier molecular orbital(FMO) suggest that DMAP not only enhances the allenic ester’s nucleophilicity but also narrows the energy gap of FMOs involved in the [2 + 4] cyclization, which makes the reaction easier to happen. Moreover, the non-covalent interaction(NCI) analysis explains the origin of regioselectivity of the reaction.更多还原

【Abstract】 Based on the experiment,[1] the mechanism of [2 + 4] cyclization of allenic esters and cyclic ketimines catalyzed by 4-dimethylaminopyridine(DMAP) for forming highly functionalized hydropyridine derivatives has been theoretically studied using density functional theory(DFT), which had been used to study the mechanisms of organocatalytic reactions.[2-7] We have considered and studied three possible channels, including the DMAP-catalyzed [β,γ]-/[α,β]-[2 + 4] cyclization(denoted as channel A/B) and the direct [β,γ]-[2 + 4] cyclization(denoted as direct channel). According to the calculated results, channel A is revealed to be the most energetically favorable among the three channels and its generated product is the main product, which is consistent with the experimental observation. The most favorable channel A contains several steps, i.e., nucleophilic addition on the Cβ atom of allenic ester by DMAP, the stepwise [β,γ]-[2 + 4] cyclization with ketimine, and the dissociation of DMAP with product. The analyses of the global reactivity index(GRI) and frontier molecular orbital(FMO) suggest that DMAP not only enhances the allenic ester’s nucleophilicity but also narrows the energy gap of FMOs involved in the [2 + 4] cyclization, which makes the reaction easier to happen. Moreover, the non-covalent interaction(NCI) analysis explains the origin of regioselectivity of the reaction.更多还原