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

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.