Hydrodefluorination

The ease of dehalogenation of C H X by Ni(ll)/ IMes HCl 1/NaO Pr decreased in the order 1 > Br > Cl F. Subsequent work showed that a 1 1 combination of Ni and NHC in the presence of NaOCHEt resulted in enhanced reactivity towards aryl fluorides [6], Again, the A-mesityl substituted ligand IMes HCl 1 imparted the highest level of catalytic activity. Table 8.2 illustrates that hydrodefluorination is sensitive to both the nature of the substituents on the aromatic ring and the specific regioisomer. Thus, 2- or 4-fluorotoluene (Table 8.2, entry 2) proceeded to only 30% conversion after 15 h, whereas quantitative conversion of 2-fluoroanisole (Table 8.2, entry 3) and high conversion of 3-fluoropyridine (Table 8.2, entry 5) was achieved in only 2-3.5 h. The reactivity of 2-fluoropyridine was compromised by more efficient nucleophilic aromatic substitution. 

The exact nature of the catalytically active Ni species in these reactions is yet to be conclusively established. Hydrodechlorination proves optimal with a NHC Ni ratio of 2 1 suggesting that 14-electron Ni(NHC)2 is involved, whereas the 1 1 NHC Ni ratio necessary for hydrodefluorination implies that it is the 12-electron mono-carbene adduct Ni(NHC) which is catalytically active [10]. Smdies by Matsubara et al. revealed that treatment of NKacac) with either one or two equivalents of IMes HCl 1 or SlMes HCl 2 in the presence of NaOHu formed the mono-NHC complex Ni(NHC)(acac)j which, upon reduction with NaH in the presence or absence of carbene, formed Ni(NHC)2 [11]. Density functional theory (DFT) calculations suggest that the strength of the Ni-NHC bond (ca. 50 kcal/mol) makes... 

Attempts to perform hydrodefluorination on other polyfluoroarenes using 9c met with mixed success (Table 8.4). Pentafluoropyridine proved to be highly active with a turnover number of 13.6, although the distribution of products revealed up to three hydrodefluorination reactions (Table 8.4, entry 4). Substrates with a lower fluorine content, such as CF.CH, and 1,2- or 1,4-CF,H were unreactive. 

A kinetic study of the hydrodefluorination of C F H in the presence of EtjSiH indicated a first-order dependence on both [fluoroarene] and [ruthenium precursor] and a zero-order dependence on the concentration of alkylsilane, implying that the rate-limiting step in the catalytic cycle involves activation of the fluoroarene. The regioselectivity for hydrodefluorination of partially fluorinated substrates such as CgFjH has been accounted for by an initial C-H bond activation as shown in the... 

Table 8.4 Catalytic hydrodefluorination of polyfluoroarenes by 9 c Entry Aryl fluoride Products (yield/%) ...

Several mechanisms are involved in the displacement of fluorine by hydrogen and these can be divided into two groups, namely radical-type and nucleophilic hydrodefluorinations. The most general is a radical mechanism involving reductive cleavage of the fluorine bond. Radical catalytic hydrogenolyses take place at the catalyst surface ... 

Generally, allylic and benzylic fluorides are more easily reduced than ordinary alkyl fluorides. The yields are also strongly dependent upon the method used, but some aliphatic structures give only low yields of hydrodefluorination products for several methods. In radical-type re-... 

Similarly to alkyl fluorides, fluorocyclohexane is resistant toward catalytic hydrogenolysis. Hydrides and metals appear to be more efficient in the hydrodefluorination of alicyclic fluorine-containing compounds. Butyllithium in refluxing hexane defluorinates fluorocyclohexane to cyclohexane.20 The complete defluorination of fluorocyclohexane (11) is accomplished by activated magnesium in propan-2-ol, but the reaction leads to the predominant formation of cyclohexene.21... 

Several methods are employed for the reductive defluorination of 2-fluoro-l-phenyl-ethanones. Electrolytic reduction at a mercury cathode selectively replaces fluorine in 2-fluoro-l -phenylethanone by hydrogen.94 The hydrodefluorination of fluoroacetophenones, e.g. 7, to dithioacetals of the corresponding defluorinated ketones with aluminum chloride and ethanethiol take place readily by stirring the mixture in dichloromethane at 0°C under nitro-... 

The reduction of perfluoronaphthalene-2-carboxylic acid by zinc in aqueous ammonia takes place as readily164 as the reduction of perfluorobenzoic acid to give the product of hydrodefluorination at position 6 in high yield (Table 3). The carboxylic group thus activates the same position for the reduction (i.e., 6) as the C2 hydrogen in 2//-heptafluoronaphthalenc159160... 

Tetrafluoro-3-oxo-4-phenylbutanoic acid is reduced at both the activated a,a -positions and the carbonyl group to give 4-phenylbutanoic acid by the Clemmensen method in quantitative yield.125 In contrast, only the highly activated C3-F bonds are selectively reduced in ethyl 2,2,4,4,4-pentafluoro-3-oxobutanoate by treatment with sodium in diethyl ether (Table 3).126 A more efficient zinc reduction of ethyl 4.4,4-trifluoro-3-oxobutanoate in refluxing acetic acid results in complete hydrodefluorination of the trifluoromethyl group to give 21.104... 

Fluoromethylbenzoic acids, metallation, 9, 26-27 Fluoro(phenyl) complexes, with platinum(II), 8, 482 Fluorosilanes, elimination in fluorinated alkene activation, 1, 732 in fluorinated aromatic activation, 1, 731 and hydrodefluorination, 1, 748 Fluorosilicate anions, hypercoordinated anions, 3, 484 Fluorotoluenes, metallation, 9, 21 Fluorous alkylstannanes, preparation, 3, 820 Fluorous biphasic system, as green solvent, 12, 844 Fluorous ligands, with supercritical carbon dioxide, 1, 82 Fluorous media... 

Treatment of fluorinated polykis(dialkylamino)naphthalenes with small excess of LiAII I4 in boiling THF results in exhaustive hydrodefluorination. This route, starting from 71, 73 and 75, provides high yields of tetrakis(dimethylamino)naphthalene 7962 and proton sponges 80 and 8164. 

Hydrodefluorination. A trifluoromethyl group of bis(trifluoromethyl)arenes is converted into the methyl group on heating with LAH (3 equiv.) and NhCls (5 mol%) in DME. By increasing the amount of LAH to 10 equivalents both trifluoromethyl groups are reduced. ... 

Oxidative addition. 5.2 Hydrodefluorination, M-F bond formation. 5.3 Nuoleophilio attaok. 5.4 Defluorination... 

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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