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Site-, enantio- and stereo-selectivities of the 1,3-dipolar cycloaddition reactions of oxanorbornadiene with C,N-disubstituted nitrones and dimethyl nitrilimines: a DFT mechanistic study

  • Ernest Opoku
  • Grace Arhin
  • George Baffour Pipim
  • Anita Houston Adams
  • Richard TiaEmail author
  • Evans Adei
Regular Article

Abstract

1,3-Dipolar cycloaddition of nitrones to oxanorbornadienes is an important method for the enantioselective synthesis of highly substituted 5-membered heterocycles such as furans and isoxazolidines, which have high utility in the chemical and pharmaceutical industries. The mechanism of the reaction and the effects of substituents on the (3 + 2) cycloaddition reactions (32CA) of C,N-dialkyl nitrones with a series of substituted oxanorbornadienes have been studied with focus on the site-selectivity (attack on the more substituted double bond of the oxanorbornadiene derivatives versus attack on the less substituted double bond), enantioselectivity and stereo-selectivity using density functional theory calculations at the M06/6-311++G(d,p) of theory. The results showed that the addition step to form the bicyclic isoxazolidines cycloadducts has generally low barriers compared to the cycloreversion step which converts the cycloadducts into furans and monocyclic isoxazolidines. Generally, electron-withdrawing substituents favour the nitrone attack on the highly substituted double bond, while electron-donating substituents favour the attack on less substituted double bond. The R enantiomers are generally favoured over the S enantiomers, and exo stereo-isomers are generally favoured over the endo stereo-isomers, irrespective of substituents.

Keywords

Dipole Oxanorbornadiene Nitrone Enantioselectivity Density functional theory 

Notes

Acknowledgements

The authors are very grateful to the National Council for Tertiary Education, Republic of Ghana, for a research Grant under the Teaching and Learning Innovation Fund (TALIF/KNUST/3/0008/2005), and to South Africa’s Centre for High Performance Computing for access to additional computing resource on the Lengau cluster.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest whatsoever regarding the publication of this manuscript.

Supplementary material

214_2019_2529_MOESM1_ESM.docx (241 kb)
Supplementary material 1 (DOCX 240 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Theoretical and Computational Chemistry Laboratory, Department of ChemistryKwame Nkrumah University of Science and TechnologyKumasiGhana

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