Nucleophilic fluoride anion

Nevertheless, rearrangements can be suppressed, in most cases, when dediazoniation is performed in hydrogen fluoride/pyridine (48 52 w/w) mixture,308,310 since this less acidic medium stabilizes carbocations (such as the phenonium cation) to a far lesser extent and provides more nucleophilic fluoride anions which, however, cannot totally match the anchimeric assistance of the aryl or hydroxy group in tyrosine (5g) and threonine (5h). 

Better yields are attributed to intimate association of the basic nitrile group at the surface of the mtrosomum salt causing nitrosative decomposition of the azide to occur in close proximity to the weakly nucleophilic complex fluoride anion Fluorination yields can be further enhanced to 59-81% by lengthening the azido nitrile chain, but the reaction is accompanied by pronounced secondary fluoronitnle formation arising from rearrangement [100, 101] (Table 8)... 

Perfluoroalkyl carbanions, generated by reversible nucleophilic addition of a fluoride anion to fluoroalkenes, react with dry benzenediazonium chloride in dimethyl formamide, giving phenylazoperfluoroalkanes in 41-53% yield (Dyatkin et al., 1972). The dianion obtained from 1,2-dinitrobenzene with dipotassium cyclo-octatetraenide reacts in a complex way with arenediazonium salts, forming 4-aryl-azo-2-nitrophenol in 46-58% yield (Todres et al., 1988). 

Other salts, especially fluoride salts, (e.g., KF) can be used to perform nucleophilic substitution. As is well known, halides, and particularly the fluoride anions, are rather powerful Lewis bases and can exert a catalytic effect on aromatic nucleophilic substitutions in dipolar aprotic solvents. Phenols can be alkylated in the presence of KF (or CsF) absorbed on Celite64,65 or Et4NF.66 Taking advantage of this reaction, halophenols and dihalides with bisphenols have been successfully polymerized in sulfolane at 220-280°C by using KF as the base. 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a Michael acceptor (Stetter reaction) is a well-known synthetic tool leading to the synthesis of highly funtionalized products. Recent developments in this area include the direct nucleophilic addition of acyl anions to nitroalkenes using silyl-protected thiazolium carbinols <06JA4932>. In the presence of a fluoride anion, carbinol 186 is not cleaved to an aldehyde... 

In the case of the experiments performed by Hohman and co-workers [149], the fluoride anion would readily displace the silicon-leaving group. The peroxide anion could then further react via an intramolecular nucleophilic attack, resulting in cyclization to form the reactive intermediate responsible for the chemiluminescence that was observed. A recent kinetic study by Stevani and Baader [150] of the reaction of 4-chlorophenyl-O,O-hydrogen monoperoxyoxalate with various oxygen and nitrogen bases suggested that the intermediate formed must be 1,2-dioxetandione. 

Classical C,C-coupling reactions of AN anions (Henry, Michael, and Mannich) involve complex systems of equilibria and, consequently, generally not performed in protic solvents. The introduction of the silyl protecting group allows one to perform these reactions in an aprotic medium to prepare or retain products unstable in the presence of active protons. In addition, the use of nucleophiles which are specifically active toward silicon (e.g., the fluoride anion) enables one to design a process in which the effective concentration of a-nitro carbanions is maintained low. 

However, Michael addition has been successfully performed in recent years with the use of nucleophilics catalysis (fluoride anion or amines) (132) (Scheme 3.195). 

The extreme hydrophobicity, or in other words, the low water solubility, of the carborane cage is a major disadvantage in terms of biodistribution. However, 0-C2B10 can be readily converted into a water-soluble degradation product. 0-C2B10 reacts with strong nucleophiles such as alkoxides, aliphatic amines and fluoride anion to... 

Johnson and McCants (161) were the first to show that the alkaline hydrolysis of alkoxysulfonium salts, obtained by 0-alkylation of sulfoxides, proceeds with inversion of configuration at sulfur. This method was employed to interconvert (/ )- and (5)-benzyl p-tolyl sulfoxides 37 as shown in Scheme 21. In contrast to the hydroxide anion, the chloride, bromide, and iodide anions as well as the nitrogen atom of pyridine react with chiral ethoxydiarylsulfonium salts, not at sulfur but at the a-carbon atom of the ethoxy group, yielding the starting sulfoxide with retained configuration (284). On the other hand, the nucleophilic attack of the fluoride anion is directed at sulfur as in the case of the hydroxide anion (285). 

Direct nucleophilic SN2 exchanges F/leaving group (mesylate, tosylate, nosy-late, triflate, iodide or bromide) in a complex structure using [ Fj fluoride anion are more frequent in aliphatic than in aromatic series. The choice of the leaving group is strongly dependent on the substrate to label [206] and it is often neces-... 

A method using dual activation has been developed in which a Lewis acid activates the aldehyde with concomitant nucleophilic activation of the allylic silicon reagent with fluoride anion. Thus, by using a BINOL-based titanium... 

Ci/mmol (6.3 x 10" TBq/mmol), the practically achieved no-carrier-added specific radioactivity is in the region of 10 Ci/mmol (3.7 x 10 TBq/mmol). Fluoiine-18 is generally recovered from the target as [ F]fluoride anion in an aqueous solution and is then engaged in nucleophilic radiofluorinations (see Section 4.1). 

Since non-bound or non-coordinated nucleophiles are even more reactive, crown-ethers [138] and cryptands (polyaminoethers) [139,140] have been used to chelate the alkali metal cations, notably the potassium ion of K[ F]F. This allows the [ F]fluoride anion to be less tightly paired with the cation and therefore to be more reactive, which has been coined the naked ion effect. In practice, the crown-ether (e.g. 18-crown-6) or better the polyaminoether Kryptofix-222 (4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) is added to the aqueous K[ F]F/K2C03 solution which is then concentrated to dryness [139,140]. The complex (KP FIF-K ) can be further dried, if needed, by one or more cycles of addition of dry acetonitrile and azeotropic evaporation. 

M.A. Vincent, I.H. Hillier, The solvated fluoride anion can be a good nucleophile, Chem Commun. (2005) 5902-5903. 

Creation of a carbon-fluorine bond through reaction of a fluoride anion (nucleophilic fluorination). 

Fluonnated alkoxides, obtained by addition of the fluoride anion to a carboxylic halide group, are weak nucleophiles, which can be alkylated [35,36] (equations 31 and 32)... 

Direct nucleophilic acylation of nitroalkenes (164), promoted by a combination of (g) fluoride anion and thiourea catalyst (165), has been developed, using the thiazolium derivative (163) as the umpolung reagent (<20 1 dr, 74% ee).214 ... 

Fluoride anion can both react with silylaryl triflate to generate benzyne and act as a base to abstract the hydrogen on the amide nitrogen to afford an anion that can attack the benzyne. Intramolecular nucleophilic attack on the carbonyl carbon (or... 

The silyl group is widely used as an oxygen protecting group, because of the ease of its removal by nucleophilic substitution by fluoride anion. The protected phenols 0-(tert-butyldimethylsilyl)-/ -(bromomethyl)phenol (45) and 0-(tert-butyldimethylsilyl)-2,6-bis(bromomethyl)phenol (46) react rapidly with fluoride anion in water to form the corresponding phenols, which then break down to the ortho-quinone methide 41 (Scheme 21A) and the substituted ortho-quinone... 

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