Unveiling the non-polar [3+2] cycloaddition reactions of cyclic nitrones with strained alkylidene cyclopropanes within a molecular electron density theory study

Luis R Domingo; Mar Ríos-Gutiérrez; Rishikesh Chulan; M H H Mahmoud; Mohamed M Ibrahim; Salah M El-Bahy; Lydia Rhyman; Ponnadurai Ramasami

doi:10.1039/d2ra03327e

Unveiling the non-polar [3+2] cycloaddition reactions of cyclic nitrones with strained alkylidene cyclopropanes within a molecular electron density theory study

RSC Adv. 2022 Sep 6;12(39):25354-25363. doi: 10.1039/d2ra03327e. eCollection 2022 Sep 5.

Authors

Luis R Domingo¹, Mar Ríos-Gutiérrez¹, Rishikesh Chulan², M H H Mahmoud³, Mohamed M Ibrahim³, Salah M El-Bahy⁴, Lydia Rhyman^{2

5}, Ponnadurai Ramasami^{2

5}

Affiliations

¹ Department of Organic Chemistry, University of Valencia Dr Moliner 50 E-46100 Burjassot Valencia Spain luisrdomingo@gmail.com.
² Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius Réduit 80837 Mauritius p.ramasami@uom.ac.mu.
³ Department of Chemistry, College of Science, Taif University P.O. Box 11099 Taif 21944 Saudi Arabia.
⁴ Department of Chemistry, Turabah University College, Taif University P.O. Box 11099 Taif 21944 Saudi Arabia.
⁵ Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg Doornfontein Johannesburg 2028 South Africa.

Abstract

The role of cyclopropane substitution on the ethylene in zw-type [3+2] cycloaddition (32CA) reactions of cyclic nitrones has been studied within Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) computational level. Electron Localization Function (ELF) analysis of the ethylenes shows that the presence the cyclopropane only slightly increases the electron density in the C-C bonding region. Analysis of the Conceptual DFT reactivity indices indicates that the presence of the cyclopropane does not produce any remarkable change in the reactivity of these strained ethylenes. The marginal electrophilic character of ethylene makes the zw-type 32CA reactions of non-polar character. The presence of the cyclopropane in the ethylene decreases the activation enthalpy of the 32CA reactions by only 1.7 and 2.6 kcal mol^-1, and also decreases the ortho regioselectivity. The loss of the strain present in the cyclopropane is responsible for the reduction of the activation enthalpy and the increase of the reaction enthalpy in these non-polar 32CA reactions. The presence of the cyclopropane does not cause any change, neither in the transition state structure (TS) geometries nor in their electronic structure. The very low global electron density transfer (GEDT) computed at the TSs confirms the non-polar character of these 32CA reactions. The ortho regioselectivity experimentally observed in these non-polar 32CA reactions is determined by the most favorable two-center interaction between the less electronegative C1 carbon of nitrone and the non-substituted methylene C5 carbon of the ethylenes.