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

Published version
Peer-reviewed

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Authors

Poh, Jian-Siang 
García-Ruiz, Cristina 
Zúñiga, Andrea 
Meroni, Francesca 
Blakemore, David C 

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.

Description

Keywords

0306 Physical Chemistry (incl. Structural)

Journal Title

Organic and Biomolecular Chemistry

Conference Name

Journal ISSN

1477-0520
1477-0539

Volume Title

14

Publisher

RSC
Sponsorship
Engineering and Physical Sciences Research Council (EP/K009494/1)
Engineering and Physical Sciences Research Council (EP/M004120/1)
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.