Fluorination and fluorodemercuration of aromatic compounds with acetyl hypofluorite

Abstract

There is an increasing interest in fluorinated aromatic compounds especially from a pharmaceutical point of view.1 However, problems regarding the introduction of fluorine into organic molecules differ considerably from those concerning other halogen atoms. Only a few practical

Para fluorination by N-fluorobis[(trifluoromethyl)sulfonyl]imide: synthesis of 10.beta.-fluoro-3-oxo-1,4-estradiene steroids

“…This is in contrast with the quite marked ortho preference shown when oxygen, or nitrogen, activated aromatics are treated with cesium fluoroxysulfate,29,30 acetyl hypofluorite,24,26 and N-fluoropyridinium salts.10 This ortho preference has been attributed either to the addition/elimination of the two fragments of the fluorinating agent across the higher electron density region of the aryl-oxygen compound23"26 or to an interaction of the negatively charged part of the fluorinating reagent with the phenolic proton.7, 10,30"32 The hypothesis that such an interaction is more difficult in protic solvents than in aprotic ones has been used to rationalize the lower ortho preference observed in protic solvents. 23,32 The results of our experiments reported in Table I and some literature data33 lead to the generalization that nonionic reagents favor the formation of fluorination products in the para position of para-substituted phenols while ionic ones display ortho selectivity. The easier association of ionic reagents with the phenolic hydroxyl could account for this difference.…”

18F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

“…Electrophilic [ 18 F]­perchloryl fluoride reacts regioselectively with functionalized aryl lithium reagents to form [ 18 F]­fluoroarenes. , N- [ 18 F]­Fluoro- N -alkylsulfonamides , react similarly with aryl lithium or aryl Grignard reagents, and N- [ 18 F]­fluoropyridinium triflate has been shown to react with aryl Grignard reagents to produce [ 18 F]­fluoroarenes by ipso fluorodemetalation. Fluoroarenes are also within reach by electrophilic fluorodemercuration. − This methodology was adopted for the regioselective radiolabeling of 6-[ 18 F]­fluoro- l -DOPA from a protected N -(trifluoroacetyl)-3,4-dimethoxy-6-trifluoroacetoxy-mercurio- l -phenylalanine ethyl ester precursor using the electrophilic reagent [ 18 F]­AcOF . Decay-corrected RCY for 6-[ 18 F]­fluoro- l -DOPA are 11–12% using this methodology, with the final product after purification containing less than 20 ppb of mercury (Figure ).…”

Highly regioselective halogenation of 1-phenyl-3-(3,5-dimethoxyphenyl)-propane-1,3-dione

“…9 Direct fluorination of aromatic rings with F 2 10 is not feasible at room temperature because of the extreme reactivity of F 2 , but this can be accomplished at low temperatures. 11 Fluorination has also been reported with acetyl hypofluorite, 12 XeF 2 , 13 NeF reagents, such as FeTEDA 14 or (CF 3 SO 2 ) 2 NF, 15 and by the Schiemann reaction as the most common method for introducing fluorine into aromatic rings. Aromatic compounds can be chlorinated or brominated by treatment with bromine or chlorine in the presence of a catalyst.…”