Geminal Chlorofluorination of Diazo Compounds Mediated by a Hypervalent Iodine(III) Reagent Bearing Transferable Fluorine and Chlorine Atoms
The exploration of unconventional functional group transfer reagents represents a significant advancement in the development of practical and atom-efficient synthetic methodologies. We herein report a novel bench-stable and modular <i>N</i>-chlorofluoroiodane-(III) reagent, <b>CFBI</b>, which facilitates the transfer of chlorine and fluorine atoms to diazonium compounds in a single-step reaction. This method affords medicinally relevant α,α-chlorofluoro ketones, amides, and esters in moderate to high yields with excellent chemoselectivity. <b>CFBI</b>, which features an <i>N</i>-chlorobenziodazolone framework, is readily synthesized in two steps with an overall yield of 64%. Its structure was fully characterized by NMR spectroscopy, ESI-HRMS, and X-ray crystallography. Combined experimental and computational studies reveal that this reaction follows a nonclassical mechanism. In the rate-determining step, the nucleophilic diazonium preferentially attacks the electrophilic chlorine atom instead of the iodane-(III), leading to the formation of a partially reduced iodane-(III) species <b>E</b>.
Authors
- Feng‐Huan Du (ORCID: https://orcid.org/0009-0001-7586-6517)
- Jianhua Zhang (ORCID: https://orcid.org/0000-0001-7844-6035)
- Xiaowei Chen
Institutions
- Nankai University (CN)
- State Research Institute of Organic Chemistry and Technology (RU)
- Institute of Organic Chemistry (PL)
- Institute of Organic Chemistry (HU)
Publication Details
- Journal
- JACS Au
- Published
- 2026-02-03
- DOI
- https://doi.org/10.1021/jacsau.5c01488
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00