A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

Zsanett Benke; Attila M Remete; Loránd Kiss

doi:10.3762/bjoc.17.132

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

Beilstein J Org Chem. 2021 Aug 13:17:2051-2066. doi: 10.3762/bjoc.17.132. eCollection 2021.

Authors

Zsanett Benke^{1

2}, Attila M Remete^{1

2}, Loránd Kiss^{1

2}

Affiliations

¹ Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary.
² University of Szeged, Interdisciplinary Excellence Centre, Institute of Pharmaceutical Chemistry, H-6720 Szeged, Eötvös u. 6, Hungary.

Abstract

This work presents an examination of the selective functionalization of norbornadiene through nitrile oxide 1,3-dipolar cycloaddition/ring-opening metathesis (ROM)/cross-metathesis (CM) protocols. Functionalization of commercially available norbornadiene provided novel bicyclic scaffolds with multiple stereogenic centers. The synthesis involved selective cycloadditions, with subsequent ROM of the formed cycloalkene-fused isoxazoline scaffolds and selective CM by chemodifferentiation of the olefin bonds of the resulting alkenylated derivatives. Various experimental conditions were applied for the CM transformations with the goal of exploring substrate and steric effects, catalyst influence and chemodifferentiation of the olefin bonds furnishing the corresponding functionalized, fluorine-containing isoxazoline derivatives.

Keywords: functionalization; metathesis; nitrile oxide; organofluorine chemistry; selectivity.

Grants and funding

We are grateful to the Hungarian Research Foundation (NKFIH K 119282) for financial support. The financial support of the GINOP-2.3.2-15-2016-00038 project is also acknowledged. This research was supported by the EU-funded Hungarian grant EFOP-3.6.1-16-2016-00008. The Ministry of Human Capacities, Hungary (grant 20391-3/2018/FEKUSTRAT) is also acknowledged. This work was supported by the ÚNKP-20-3 - New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund.