A DFT study of the double (3 + 2) cycloaddition of nitrile oxides and allenoates for the formation of spirobiisoxazolines

Isaac Ofori; George Baffour Pipim; Richard Tia; Evans Adei

doi:10.1016/j.jmgm.2021.108033

A DFT study of the double (3 + 2) cycloaddition of nitrile oxides and allenoates for the formation of spirobiisoxazolines

J Mol Graph Model. 2021 Dec:109:108033. doi: 10.1016/j.jmgm.2021.108033. Epub 2021 Sep 12.

Authors

Isaac Ofori¹, George Baffour Pipim², Richard Tia³, Evans Adei⁴

Affiliations

¹ Theoretical and Computational Chemistry Laboratory, Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: iofori995@gmail.com.
² Theoretical and Computational Chemistry Laboratory, Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: baffourgeorge88@gmail.com.
³ Theoretical and Computational Chemistry Laboratory, Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: richardtia.cos@knust.edu.gh.
⁴ Theoretical and Computational Chemistry Laboratory, Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: eadei@yahoo.com.

PMID: 34534890
DOI: 10.1016/j.jmgm.2021.108033

Abstract

The molecular mechanism of the double (3 + 2) cycloaddition (32CA) reaction between nitrile oxides and allenoates has been studied using density functional theory at the M06-2X/6-311G (d,p) level of theory. In the first 32CA, the nitrile oxide adds chemo- and regio-selectively to the C-C double bond of the allenoate closest to the carboxylate group followed by a subsequent regioselective addition to the olefinic bond of the isoxazoline intermediate. The rate constant for the preferred pathway (formation of 4-methylene-2-isoxazoline intermediate) in the reaction of ethyl substituted allenoate and mesitonitrile oxide is 5.3 × 10² s^-1 in THF which is about 13 times faster than the closest competing step (formation of its regioisomer 5-methylene-2-isoxazoline intermediate) which has a rate constant of 4.4 × 10¹ s^-1. Strong electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) decrease activation barriers and hence increase the reaction rate. Also, the dimerization of nitrile oxide to form furaxon is found to be kinetically unfavored.

Keywords: (3 + 2) cycloaddition; Parr and fukui functions; Spirocyclic-compounds; Spiroisoxazolines.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cycloaddition Reaction
Electrons
Molecular Structure
Nitriles*
Oxides*

Substances

Nitriles
Oxides