A MEDT investigation of mechanism and selectivities of the intramolecular [3+2] cycloaddition reaction of (E)-N-((2-((methylbut-2-en-1-yl)thio)-1H-indol-3-yl)methylene)methanamine-oxide

In this paper, an MEDT computational study was conducted through the B3LYP/6-31G(d,p) DFT method, to analyse the mechanism nature and the selectivities of the intramolecular [3+2] cycloaddition (I32CA) of the (E)-N-((2-((methylbut-2-en-1-yl)thio)-1H-indol-3-yl)methylene)methanamine oxide. The investigation covered the three potential pathways, including the fused endo and exo steric approaches and the bridged channels associated with the I32CA reaction. Analysis of relative energy indicated that the isoxazolidine formed from the fused-endo pathway is favored kinetically, which are consistent with the published experimental findings. Based on bond order values and geometry of the transition states, the obtained results suggest that this I32CA occurs via one-step slightly synchronous mechanism in the case of the fused modes, whereas in the bridged one via a one-step slightly asynchronous mechanism. Relative thermodynamic functions show that the studied I32CA has exothermic and exergonic behaviours. ELF analysis of the fused-endo pathway reveals that the mechanism of this I32CA reaction is non-concerted slightly synchronous two stages one-step. NCI and QTAIM analyses show that the existence of several NCIs at the favourable fused-endo structure is the main reason for the fused-endo selectivity.