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Synthesis of trifluoromethylated isoxazoles and their elaboration through inter- and intra-molecular C-H arylation

Poh, J-S; Garcia-Ruiz, C; Zuniga, A; Meroni, F; Blakemore, DC; Browne, DL; Ley, SV; (2016) Synthesis of trifluoromethylated isoxazoles and their elaboration through inter- and intra-molecular C-H arylation. Organic & Biomolecular Chemistry , 14 (25) pp. 5983-5991. 10.1039/c6ob00970k. Green open access

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Abstract

We report conditions for the preparation of a range of trifluoromethylated isoxazole building blocks through the cycloaddition reaction of trifluoromethyl nitrile oxide. It was found that controlling the rate (and therefore concentration) of the formation of the trifluoromethyl nitrile oxide was Critical for the preferential formation of the desired isoxazole products versus the furoxan dimer. Different conditions were optimised for both aryl- and alkyl-substituted alkynes. In addition, the reactivity at the isoxazole 4-position has been briefly explored for these building blocks. Conditions for intermolecular C–H arylation, lithiation and electrophile quench, and alkoxylation were all identified with brief substrate scoping that signifies useful tolerance to a range of functionalities. Finally, complementary processes for structural diversification through either intramolecular cyclisation or intermolecular cross-coupling were developed.

Type: Article
Title: Synthesis of trifluoromethylated isoxazoles and their elaboration through inter- and intra-molecular C-H arylation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1039/c6ob00970k
Publisher version: http://dx.doi.org/10.1039/c6ob00970k
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 3.0 Unported Licence
Keywords: DIVERSITY-ORIENTED SYNTHESIS, POSITRON-EMISSION-TOMOGRAPHY, PROTON-ABSTRACTION MECHANISM, LATE-STAGE FLUORINATION, MEDICINAL CHEMISTRY, SANDMEYER TRIFLUOROMETHYLATION, TRIFLUOROACETONITRILE OXIDE, POLYHETEROCYCLIC SYSTEMS, PHARMACEUTICALS, DISCOVERY
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10114354
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