A Molecular Electron Density Theory Study of the [3+2] Cycloaddition Reaction of an Azomethine Ylide with an Electrophilic Ethylene Linked to Triazole and Ferrocene Units

Luis R Domingo; Mar Ríos-Gutiérrez; Assem Barakat

doi:10.3390/molecules27196532

A Molecular Electron Density Theory Study of the [3+2] Cycloaddition Reaction of an Azomethine Ylide with an Electrophilic Ethylene Linked to Triazole and Ferrocene Units

Molecules. 2022 Oct 3;27(19):6532. doi: 10.3390/molecules27196532.

Authors

Luis R Domingo¹, Mar Ríos-Gutiérrez¹, Assem Barakat²

Affiliations

¹ Department of Organic Chemistry, University of Valencia, Dr. Moliner 50, 46100 Burjassot, Valencia, Spain.
² Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

Abstract

The [3+2] cycloaddition (32CA) reaction of an azomethine ylide (AY) with an electrophilic ethylene linked to triazole and ferrocene units has been studied within the Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) level. The topology of the electron localization function (ELF) of this AY allows classifying it as a pseudo(mono)radical species characterized by the presence of two monosynaptic basins, integrating a total of 0.76 e, at the C1 carbon. While the ferrocene ethylene has a strong electrophilic character, the AY is a supernucleophile, suggesting that the corresponding 32CA reaction has a high polar character and a low activation energy. The most favorable ortho/endo reaction path presents an activation enthalpy of 8.7 kcal·mol^-1, with the 32CA reaction being exergonic by -42.1 kcal·mol^-1. This reaction presents a total endo stereoselectivity and a total ortho regioselectivity. Analysis of the global electron density transfer (GEDT) at the most favorable TS-on (0.23 e) accounts for the high polar character of this 32CA reaction, classified as forward electron density flux (FEDF). The formation of two intermolecular hydrogen bonds between the two interacting frameworks at the most favorable TS-on accounts for the unexpected ortho regioselectivity experimentally observed.

Keywords: Molecular Electron Density Theory (MEDT); [3+2] cycloaddition (32CA); azomethine ylide (AY); ferrocene; spirooxindoles; triazole.

Grants and funding

This work has been supported by the Ministry of Science and Innovation (MICINN) of the Spanish Government (project PID2019-110776GB-I00 (AEI/FEDER, UE)). The authors would like to extend their sincere appreciation to the Researchers Supporting Project (RSP-2021/64), King Saud University, Riyadh, Saudi Arabia.