The [3+2] annulation of in situ formed trifluorodiazoethane with 4-nitroisoxazoles: access to trifluoromethylpyrazolo[3,4- d]isoxazoles

Huamin Wang; Li-Qin Meng; Wenjing Niu; Wan-Qi Yang; Yu Ou; Ying-Wu Lin

doi:10.1039/d4cc03826f

The [3+2] annulation of in situ formed trifluorodiazoethane with 4-nitroisoxazoles: access to trifluoromethylpyrazolo[3,4- d]isoxazoles

Chem Commun (Camb). 2024 Oct 22;60(85):12425-12428. doi: 10.1039/d4cc03826f.

Authors

Huamin Wang¹, Li-Qin Meng¹, Wenjing Niu¹, Wan-Qi Yang¹, Yu Ou¹, Ying-Wu Lin^{1

2}

Affiliations

¹ School of Chemistry and Chemical Engineering, University of South China, Hengyang, P. R. China. huaminwang@usc.edu.cn.
² Laboratory of Protein Structure and Function, University of South China Medical School, Hengyang, P. R. China.

PMID: 39377173
DOI: 10.1039/d4cc03826f

Abstract

A general and practical K₂CO₃-promoted [3+2] annulation between trifluoroacetaldehyde N-triftosylhydrazone (TFHZ-Tfs) and 4-nitroisoxazoles has been developed to access structurally diverse trifluoromethylpyrazolo[3,4-d]isoxazoles. Mechanistically, CF₃CHN₂ is formed in situ by TFHZ-Tfs decomposition and involves a formal [3+2] dearomative cycloaddition with 4-nitroisoxazoles, followed by aromatization via the elimination of the nitro group. Furthermore, this protocol is metal-free, scalable, mild, and operationally safe, with a broad substrate scope and high functional group compatibility.