Geminal Chlorofluorination of Diazo Compounds Mediated by a Hypervalent Iodine(III) Reagent Bearing Transferable Fluorine and Chlorine Atoms

利用带有可转移氟原子和氯原子的高价碘(III)试剂介导的重氮化合物的偕氯氟化反应

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Abstract

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 N-chlorofluoroiodane-(III) reagent, CFBI, 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. CFBI, which features an N-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 E.

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