DFT mechanistic studies on the regio-, stereo-, and enantio-selectivity of 1,3 dipolar cycloadditions of quinolinium imides with olefins, maleimides, and benzynes for the synthesis of fused N,N'-heterocycles.

This work investigated computationally the regio-, stereo-, and enantio-selectivity of the reactions of azomethine imines with olefins, maleimides, and benzynes, important reactions towards the synthesis of heteropolycyclic, N,N'-fused, spirocyclic systems, which serve as building blocks for the synthesis of many pharmaceuticals, agrochemicals, and biologically active compounds. The results show that the thermally controlled diastereoselective [3 + 2] cycloaddition reaction between quinolinium imide and methyl acrylate provides two regio-isomers: 1,4-regioisomer (N-C1, C-C2) and 1,3-regioisomer (N-C2, C-C1). The 1,4-regioisomer has cis and trans-stereoisomers while the 1,3-regioisomer has R-enantiomer and S-enantiomer, and the barriers for the formation of these isomers are 5.1, 19.1, 10.7, and 10.5 kcal/mol, respectively. The reaction between quinolinium imide and maleimide leads to the formation of two stereoisomers; cis-isomer and trans-isomer in which the cis-isomer is kinetically and thermodynamically favoured by 6.1 kcal/mol and 8.7 kcal/mol, respectively. The reaction between quinolinium imide and benzyne also leads to the formation of two stereoisomers through one transition state, with a barrier of 3.0 kcal/mol. Global electrophilicity index calculations show that the dipole acts as a good electrophile in the reaction and decreasing or increasing electrophilicity index has no correlation with the activation barriers. Graphical abstractPathways of the 1,3 dipolar cycloadditions of quinolinium imides with olefins, maleimides, and benzynes for the synthesis of fused N,N'-heterocycles.