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Halide-Accelerated Acyl Fluoride Formation Using Sulfuryl Fluoride

Paul J. Foth, Thomas C. Malig, Hao Yu, Trevor G. Bolduc, Jason E. Hein, Glenn M. Sammis

2020Organic Letters35 citationsDOI

Abstract

Herein, we report a new one-pot sequential method for SO2F2-mediated nucleophilic acyl substitution reactions starting from carboxylic acids. A mechanistic study revealed that SO2F2-mediated acid activation proceeds via the anhydride, which is then converted to the corresponding acyl fluoride. Tetrabutylammonium chloride or bromide accelerate the formation of acyl fluoride. Optimized halide-accelerated conditions were used to synthesize acyl fluorides in 30–80% yields, and esters, amides, and thioesters in 72–96% yields without reoptimization for each nucleophile.

Topics & Concepts

ChemistryFluorideHalideNucleophileNucleophilic acyl substitutionBromideSulfuryl chlorideHalogenNucleophilic substitutionAcylationChlorideAcyl chlorideOrganic chemistryCatalysisInorganic chemistryAlkylChemical Synthesis and AnalysisFluorine in Organic ChemistryClick Chemistry and Applications
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