Synthesis of trifluoromethylated isoxazoles and their elaboration through inter- and intra-molecular C-H arylation.
Poh, Jian Siang
Blakemore, David C
Browne, Duncan L
Organic and Biomolecular Chemistry
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Poh, J. S., García-Ruiz, C., Zúñiga, A., Meroni, F., Blakemore, D. C., Browne, D. L., & Ley, S. (2016). Synthesis of trifluoromethylated isoxazoles and their elaboration through inter- and intra-molecular C-H arylation.. Organic and Biomolecular Chemistry, 14 (25), 5983-5991. https://doi.org/10.1039/c6ob00970k
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.
We thank the Cambridge Home and European Scholarship Scheme (JSP) and the EPSRC (SVL grant numbers EP/K009494/1 and EP/M004120/1) for financial support.
External DOI: https://doi.org/10.1039/c6ob00970k
This record's URL: https://www.repository.cam.ac.uk/handle/1810/256367
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/