Electrophilic fluoridation

The electrophilic fluoridation reagent Selectfluor [152, l-chloromethyl-4-flu-oro-l,4-diazabicyclo[2.2.2]octane bis(tetrafluoroborate)] was allowed to react with tii-O-acetyl-D-galactal, and the resulting salt 153 l-(3,4,6-tri-0-acetyl-2-deoxy-2-fluoro-a-D-galactopyranosyl)-4-chloromethyl-l,4-diazabicyclo[2.2.2]octane bis(tet-rafluoroborate) reacted with NaNs alTording the 1,2-trans fluoro azide 154. ... 

Fluorination of C—H bonds of 8-methylquinoline was described by Sanford using an oxidative pathway with an electrophilic fluoride source as well as using nucleophilic AgF in concert with an oxidant via oxidative addition of a hypervalent PhIfOPivlj to Pd(II), followed by a ligand substitution with the nucleophilic fluoride source, and subsequent reductive elimination from Pd(lV) to form the new C—bond (Table 3.8). An alternative mechanistic proposal includes the oxidation of the cyclometal-lated Pd(II) with Phlp2 formed in situ via ligand substitution of on the prerequisite PhI(OPiv)2. This innovative approach provides a solution to the use of extranely cost-prohibitive sources of Fh ... 

As noted, one of the key issues with developing a Pd-mediated fluorination process is the difficulty associated with the reductive elimination step. In 2006, Sanford reported on a pyridine directed C-H activation strategy by reacting a palladium(ii) complex which forms a cyclic metallated intermediate this then reacts with an electrophilic fluoride to yield the aromatic fluorine (Scheme 15.75). °... 

The relative basicities of aromatic hydrocarbons, as represented by the equilibrium constants for their protonation in mixtures of hydrogen fluoride and boron trifluoride, have been measured. The effects of substituents upon these basicities resemble their effects upon the rates of electrophilic substitutions a linear relationship exists between the logarithms of the relative basicities and the logarithms of the relative rate constants for various substitutions, such as chlorination and... 

The stmcture of the ketones produced from unsymmetrical internal perfluoroepoxides has been reported (5). The epoxide ring may also be opened by strong protic acids such as fluorosulfonic acid or hydrogen fluoride at elevated temperatures (23—25). The ring opening of HFPO by sulfur trioxide at 150°C has been interpreted as an example of an electrophilic reaction (26) (eq. 3). 

Fluoronaphthalene [321-38-0] is prepared from 1-naphthylamine by the Balz-Schiemaim reaction in 52% yield or by diazotization in anhydrous hydrogen fluoride in 82% yield. Electrophilic substitution occurs at the 4-position, eg, nitration with fuming nitric acid in acetic acid gave 88% yield of l-fluoro-4-nitro-naphthalene [341 -92-4]. 

Whereas the above reactions are appHcable to activated aromatics, deactivated aromatics can be formylated by reaction with hexamethylenetetramine in strong acids such as 75% polyphosphoric acid, methanesulfonic acid, or trifluoroacetic acid to give saUcylaldehyde derivatives (117). Formyl fluoride (HCOF) has also been used as formyl a ting agent in the Friedel-Crafts reaction of aromatics (118). Formyl fluoride [1493-02-3] in the presence of BF was found to be an efficient electrophilic formyl a ting agent, giving 53% para-, 43% ortho- and 3.5% meta-tolualdehydes upon formylation of toluene (110). 

The enhancement of the electrophilic properties of thaHium(III) ttifluoroacetate makes it a very important thaHation reagent. The products of thaHation, eg, arylthaHium bis(ttifluoracetate), undergo a variety of substitution reactions, yielding iodides, fluorides, nitriles, thiophenols, phenols, and biaryls. 

Enol ethers are readily attacked in buffered medium by electrophilic reagents such as halogens, A -haloamides, perchloryl fluoride and organic peracids to give a-substituted ketones. Similarly, electrophilic attack on... 

Fluorinatton of graphite with fluorine gives graphite fluorides that have interesting properties, as recently reviewed [63]. Pyridine and its derivatives add elemental fluorine to form unstable N-fluoro adducts [14, 26, 64, 65]. These may decompose to 2-fluoropyndines [65] or be stabilized by treatment with inflate salts to form useful electrophilic fluonnating agents [64]... 

With very electrophilic olefins, an alternative hydrogen fluoride addition process is often preferred This process, involving reaction of the olefin with fluoride ion in the presence of a proton donor, is applicable to certain perhalogen ated alkenes [/] and substrates with other electron attracting groups attached to the double bond [i5, 36] (equations 4 and 5)... 

Additions of halogen fluorides to the more electrophilic perfluonnated olefins generally require different conditions Reactions of iodine fluoride, generated in situ from iodine and iodine pentafluoride [62 102 103, /05] or iodine, hydrogen fluoride, and parapeiiodic aud [104], with fluormated olefins (equations 8-10) are especially well studied because the perfluoroalkyl iodide products are useful precursors of surfactants and other fluorochemicals Somewhat higher temperatures are required compared with reactions with hydrocarbon olefins Additions of bromine fluoride, from bromine and bromine trifluonde, to perfluonnated olefins are also known [lOti]... 

A variety of reagent combinations add fluorine and sulfur to fluonnated olefins. Typically the olefin is reacted with fluoride ion and a source of electrophilic sulfur, such as sulfur tetrafluonde[757,178,179, 7S0], alkyl or amino sulfur tnfluondes [757, 787],... 

In contrast, additions of fluorine and carbon to fluormated olefins are widely investigated The best known processes involve reactions of olefins with fluoride ion to generate carbanionic intermediates [203] that are trapped in situ by carbon-based electrophiles. 

A classic example of this process is dimerization or oligomenzation of the olefins in the presence of fluoride ion [13], 204, 205], in which the electrophile is... 

Hexafluoro-2-butyne readily undergoes anionic oligomerization in the presence of fluoride ion 24 ], but the intermediate vinylic carbamon can be trapped by highly electrophilic fluormated heterocycles [249] (equation 52)... 

Fluorinated lactone rings are al.so opened by fluoride ion to give alkoxides that can he trapped by electrophiles [280] (equation 62). 

Electrophilic nitrosation of the carbanion generated from the reaction of an organic base with a strong organic acid, such as a-hydrohexafluoroisobutyronitnle [2], a hydrohexafluoroisobutyric acid or its acid chloride [2], or a hydrotetra fluoroethanesulfonyl fluoride [4], yields the corresponding a-nitroso compound as the major product (equations 2 and 3) The a-hydrohexafluoroisobutyric acid or acid chloride reacts with excess trifluoroacetyl nitrite in dimethylformamide to afford the O substituted oxime [3] (equation 4)... 

Heavily fluonnated aminobenzenes, pyridines, and pyrimidines are diazotized in strong-acid media Solid sodium nitrite added directly to the fluonnated amine dissolved in 80% hydrofluonc acid, anhydrous hydrogen fluoride, or (1 1 wt/wt) 98% sulfuric acid in (86 14 wt/wt) acetic and propionic acids affords the electrophilic fluoroarenediazonium ion Addition of an electron rich aromatic to the resultant diazonium solution gives the fluoroareneazo compound [10 II] (equa tions 9 and 10)... 

Tnflic acid is an excellent catalyst for the nitration of aromatic compounds [.S7]. In a mixture with nitnc acid, it forms the highly electrophilic nitronium inflate, which can be isolated as a white crystalline solid Nitronium inflate is a powerful nitrating reagent in inert organie solvents and in tnflic acid or sulfuric acid. It nitrates benzene, toluene, chlorobenzene, nitrobenzene, m-xylene, and benzotn-fluoride quantitatively in the temperature range of-110 to 30 °C with exeeptionally high positional selectivity [87],... 

Sakurai reactions proceed regiospecifically with a large variety of electrophiles due to the so-called /1-effect5-9. However, allylsilanes are also known as masked allyl carbanions, which may be activated by the presence of fluoride ion10-12. 

Therefore, in order to obtain a 1,4-addition of an allyl residue to an enone, two activation modes can be used reactions take place either under electrophilic conditions with Lewis acid promotion, or in the presence of fluoride ions. This is important as the stereochemical outcome often depends on the activation mode selected. 

Mechanistically there is ample evidence that the Balz-Schiemann reaction is heterolytic. This is shown by arylation trapping experiments. The added arene substrates are found to be arylated in isomer ratios which are typical for an electrophilic aromatic substitution by the aryl cation and not for a homolytic substitution by the aryl radical (Makarova et al., 1958). Swain and Rogers (1975) showed that the reaction takes place in the ion pair with the tetrafluoroborate, and not, as one might imagine, with a fluoride ion originating from the dissociation of the tetrafluoroborate into boron trifluoride and fluoride ions. This is demonstrated by the insensitivity of the ratio of products ArF/ArCl in methylene chloride solution at 25 °C to excess BF3 concentration. 

Finally, the reaction of 19b with potassium fluoride in the presence of a crown-ether phase-transfer agent118 to yield the sulfonyl fluoride 67 and diphenylacetylene119 belongs to the same category in which a nucleophile (F in this case) attacks the electrophilic sulfur of the sulfone group (equation 19). 

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