Addition fluoroaromatics

Fluoroaromatics are produced on an industrial scale by diazotization of substituted anilines with sodium nitrite or other nitrosating agents in anhydrous hydrogen fluoride, followed by in situ decomposition (fluorodediazoniation) of the aryldiazonium fluoride (21). The decomposition temperature depends on the stabiHty of the diazonium fluoride (22,23). A significant development was the addition of pyridine (24), tertiary amines (25), and ammonium fluoride (or bifluoride) (26,27) to permit higher decomposition temperatures (>50° C) under atmospheric pressure with minimum hydrogen fluoride loss. 

In organo-fluorine compounds fluorine atoms can be eliminated by nucleophilic sulfur species to form C —S bonds. In principle, the fluorine to be eliminated can be bonded to aliphatic or araliphatic compounds, as well as to aromatic or heterocyclic compounds however, the replacement proceeds more efficiently the more the fluorine is activated. Therefore, the synthetic usefulness of these reactions is the broadest with fluoroaromatic compounds, including heteroaromatics, with which the reactions often proceed smoothly under mild conditions. The nucleophilic sulfur compound to be reacted is. in most cases, an aliphatic or aromatic thiol or a metal sulfide, but reactions with, for example, thiourea or ammonium thiocyanate have also been described. The sulfur introduced this way can be either oxidized or removed by reduction, opening additional possibilities for modifications of the original fluoro compounds. 

The addition of tin(II) chloride or tin(II) fluoride, as low-redox-polential reducUtnts. in the dediiizoniation slop of the fluorination of arylamines with polar groups, using hydrogen fluoride in the presence of a nucleophilic fluoride source (e.g., tetrabutylanimonium diliydrogen trifluoride), not only improves the yield of the fluoroaromatic, but al.so allows the fiuorodediazoni-ation process to be performed under milder reaction conditions. ... 

One of the earliest means of introducing fluorine selectively into specific positions of aromatic compounds is the Balz-Schiemann reaction [77] which dates back to the 1920s. An isolated arene diazonium tetrafluoroborate is thermolyzed at up to 120 °C to yield the corresponding fluoroaromatic compound. Because of the infamously hazardous nature of isolated diazonium salts the scope of the classical variant of the Balz-Schiemann reaction was limited to the small scale. The high exothermicity of the reaction is most conveniently controlled by diluting the diazonium salt with a solid inert medium such as sea sand. In addition to the danger to the experimenter, the reproducibility of the reaction yield is quite poor. 

Because of the extraordinary strength of the carbon-fluorine bond, transition metal-mediated activation of fluoroalkanes and arenes is not easy to achieve. Nevertheless, activation of the C-F bond in highly electron-deficient compounds such as 2,4,6-trifluoropyrimidine, pentafluoropyridine, or hexafluorobenzene is possible with stoichiometric amounts of bis(triethylphosphano) nickel(O) [101] (Scheme 2.45). More recently Herrmann and coworkers [102] have described a variant of the Kumada-Corriu cross-coupling reaction [103] between fluorobenzene and aryl Grignard compounds which uses catalytic amounts of nickel carbene complexes. Hammett analysis of the relative kinetic rate constants indicated that the reaction proceeds via initial oxidative addition of the fluoroaromatic reactant to the nickel(O) species. 

We classify the fundamental processes of intermolecular G-F bond activation in the following six categories (i) oxidative addition of fluorocarbon, (ii) M-G bond formation with HF elimination, (iii) M-G bond formation with fluorosilane elimination, (iv) hydrodefluorination of fluorocarbon with M-F bond formation, (v) nucleophilic attack on fluorocarbon, and (vi) defluorination of fluorocarbon (Scheme 4). Table 2 shows the occurrence of these processes for intermolecular G-F activation, classified according to the type of G-F bond. For instance, oxidative addition is a characteristic process for fluoroaromatics but not for fluoroalkanes, while defluorination is characteristic of fluoroalkanes but not fluoroaromatics. We include processes as intermolecular even if they involve coordination of the fluorocarbon in one of the modes in Section 1.26.1.1 prior to G-F bond breaking. Notice that processes (ii), (iii), and (iv) could be described as cr-bond metatheses we have avoided this descriptor, since it has mechanistic connotations that are only appropriate in some cases. It should also be recognized that secondary processes may make some reactions awkward to classify under this scheme. 

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