Nickel reaction with benzyl bromide

Cyclizations by formation of carbon—selenium bonds represent a modern method with a high synthetic potential in the chemistry of cyclophanes. Selenocyanates such as 16 are accessible usually in excellent yields through the reaction of bromides with KSeCN [27], The reaction with benzylic bromides under reductive conditions using the dilution principle results in good to excellent yields of [3.3]di-selenacyclophanes which can be deselenized photochemically, pyrolytically (without previous oxidation), or by reaction with arynes, Stevens rearrangement and subsequent reaction with Raney nickel. [2.2]Metacyclophane (18), for example, is accessible in 47% total yield by using this sequence of reactions starting with... 

The massive zinc (rod or plate) reacts spontaneously with activated bromides provided the preliminary electroreduction of a catalytic amount of zinc salt (ZnBr2 or ZnCl2) occurs. Reactions are carried out in nitrile solvents (CH3CN, PhCN,. ..) or their mixture with dichloromethane. An undivided cell fitted with a zinc anode and an indifferent cathode (gold, nickel, carbon, zinc,. ..) is used. As observed with benzylic bromides, the activation leads to an organozinc compound able to react with either the nitrile solvent or an electrophile reagent. The process is depicted in equation 12. 

The competing processes were sufficiently slower than the reaction of interest only in the case of the nickel complex, [Ni(NiL2)2]Cl2. Attempts to determine the rate of reaction of [Pd(NiL2)2]Cl2 with benzyl bromide revealed a very slow process occurring at a rate comparable to, but slightly slower than, the solvolysis of benzyl bromide. It is concluded that the rate of reaction of this complex with benzyl bromide is too slow for accurate rate study in methanol. 

This method is particularly useful if the Sn2 reaction with cyanide is favourable as with benzyl bromide 62. The reduction can be carried out with a variety of reagents here hydrogenation over Raney nickel gives a good result.7... 

The electrochemistry of cobalt-salen complexes in the presence of alkyl halides has been studied thoroughly.252,263-266 The reaction mechanism is similar to that for the nickel complexes, with the intermediate formation of an alkylcobalt(III) complex. Co -salen reacts with 1,8-diiodo-octane to afford an alkyl-bridged bis[Co" (salen)] complex.267 Electrosynthetic applications of the cobalt-salen catalyst are homo- and heterocoupling reactions with mixtures of alkylchlorides and bromides,268 conversion of benzal chloride to stilbene with the intermediate formation of l,2-dichloro-l,2-diphenylethane,269 reductive coupling of bromoalkanes with an activated alkenes,270 or carboxylation of benzylic and allylic chlorides by C02.271,272 Efficient electroreduc-tive dimerization of benzyl bromide to bibenzyl is catalyzed by the dicobalt complex (15).273 The proposed mechanism involves an intermediate bis[alkylcobalt(III)] complex. 

Benzyl-6-methylcyclohexanone has been prepared by the hydrogenation of 2-benzylidene-6-methylcyclohexanone over a platinum or nickel catalyst, and by the alkylation of the sodium enolate of 2-formyl-6-methylcyclohexanone with benzyl iodide followed by cleavage of the formyl group with aqueous base. The 2,6-isomer was also obtained as a minor product (about 10% of the monoalkylated product) along with the major product, 2-benzyl-2-methylcyclohexanone by successive treatment of 2-methylcyclohexanone with sodium amide and then with benzyl chloride or benzyl bromide. Reaction of the sodium enolate of 2-formyl-6-methylcyclohexanone with potassium amide in liquid ammonia formed the corresponding dianion which was first treated with 1 equiv. of benzyl chloride and then deformylated with aqueous base to form 2-benzyl-2-methylcyclohexanone.i ... 

The formation of arylzinc reagents can also be accomplished by using electrochemical methods. With a sacrificial zinc anode and in the presence of nickel 2,2-bipyridyl, polyfunctional zinc reagents of type 36 can be prepared in excellent yields (Scheme 14) . An electrochemical conversion of aryl halides to arylzinc compounds can also be achieved by a cobalt catalysis in DMF/pyridine mixture . The mechanism of this reaction has been carefully studied . This method can also be applied to heterocyclic compounds such as 2- or 3-chloropyridine and 2- or 3-bromothiophenes . Zinc can also be elec-trochemically activated and a mixture of zinc metal and small amounts of zinc formed by electroreduction of zinc halides are very reactive toward a-bromoesters and allylic or benzylic bromides . ... 

Reduction of the complex on Raney nickel yielded benzylamine, N-methyl-benzylamine, and N,N-dimethylbenzylamine but no / -phenylbenzylamine, a reduction product resulting under the same reaction conditions from benzyl cyanide. Hydrolysis with dilute sulfuric acid in acetic acid yielded benzylamine only, and oxidation of the complex with potassium permanganate gave 4.2 moles of benzoic acid per mole of complex. The bromide anion can be exchanged metathetically with various other anions such as perchlorate, iodide, and thiocyanate. When heated at 100° C. in vacuum, the complex lost one mole of benzyl bromide and yielded only one dicyanotetrakis(benzylisonitrile)iron(II) complex. 

In 1959, the coordinated mercaptide ion in the gold(III) complex (4) was found to undergo rapid alkylation with methyl iodide and ethyl bromide (e.g. equation 3).9 The reaction has since been used to great effect particularly in nickel(II) (3-mercaptoamine complexes.10,11 It has been demonstrated by kinetic studies that alkylation occurs without dissociation of the sulfur atom from nickel. The binuclear nickel complex (5) underwent stepwise alkylation with methyl iodide, benzyl bromide and substituted benzyl chlorides in second order reactions (equation 4). Bridging sulfur atoms were unreactive, as would be expected. Relative rate data were consistent with SN2 attack of sulfur at the saturated carbon atoms of the alkyl halide. The mononuclear complex (6) yielded octahedral complexes on alkylation (equation 5), but the reaction was complicated by the independent reversible formation of the trinuclear complex (7). Further reactions of this type have been used to form new chelate rings (see Section 7.4.3.1). 

When RX is easily reduced, as in the case of allyl iodides and benzyl bromides, the competing further reduction of the intermediate radical is suppressed and radical reactions such as dimerization, addition to double bonds and aromatic compounds or reaction with anions can be favored. The radical pathway can be also promoted by catalysis with reduced forms of vitamin Bn, cobaloximes or nickel complexes. These react with the alkyl halide by oxidative addition and release the alkyl radical by homolytic cleavage. 

In 1970 Hashimoto published a report on the reaction of potassium hexacy-anodinickelate with organic halides in aqueous solutions [295]. Benzyl bromides were transformed into dibenzyl ketones in the presence of CO in a water-acetone solution. If the reaction was carried out in a water-methanol solution, trans-fi-bromostyrene was transformed into methyl trani-cinnamat. Surprisingly, cinna-maldehyde was also formed in a 10 % yield (Scheme 2.47). The reaction of nickel carbonyl [Ni(CO)4l with organic halides was studied by Bauld in 1963 [296]. Aryl iodides were reacted with Ni(CO)4 in methanol and produced the corresponding methyl benzoate in good yields. If the reaction was carried out in THF, arils were formed. The reaction of allyl halides with Ni(CO)4 in the presence of MgO will produce but-3-enylsuccinic acid [297]. 

In contrast with the results obtained with simple allqfl halides, benzyl bromide leads to the formation of 77 and the ketone 78 in variable ratios (Scheme 26). A similar result has been reported in the reactions between the oxidative addition product of Ni(COD)bpy or Ni(COD)TMEDA with cw-4-cyclohexen-l,2-dicarboxylic anhydride and alkyl iodidesWith allyl bromide as the electrophile, ketone 79 is the only product isolated. However, when the reaction is performed with isolated nickelacycle 66 in the absence of Ni(CO)2Me2Phen, allylated alanine 80 is formed exclusively (60% yield) (Scheme 26). These results show that the carbonyl nickel complex is not inert because with certain reagents it transfers CO to the nickeMactone 66. Alternatively, the formation of ketones in these reactions could be explained by alkylation of the primary oxidative addition product or by carbonylation of allyl or benzyl bromide to give acyl bromides which react with 66 to give the observed products. However, this last reaction pathway seems unlikely because acetyl or benzoyl chloride do not react with in situ generated nickelacycle 66. 

Salt-activated Fe(TMP)2-2MgCl2-4LiCl was successfully used in THF at room temperature to convert activated 1,3- and 1,4-disubstituted arenes into the corresponding diaryliron(It) species. The latter were cross-coupled under nickel catalysis with alkyl iodides and bromides or even benzyl chloride. The reaction tolerates a large range of functional groups (Table 27.9) [22]. 

The reductive coupling reaction of benzyl chloride with benzoyl chloride proceeded even at room temperature however, improved results were obtained under refluxing glyme (at 85°C). The choice of nickel halide that was reduced was important. Metallic nickel prepared from nickel iodide, bromide, and chloride gave benzyl phenyl ketone in 73, 42, and 11% yields, respectively. Thus, the reaction of benzyl halides with acyl halides using metallic nickel derived from nickel iodide was carried out under refluxing glyme, and the results are summarized in Table 7.8. 

The reaction of benzyl chloride with metallic nickel in the presence of methyl acrylate was carried out at 85°C, and the expected addition product methyl 4-phenylbutanoate was formed in 17% yield (Equation 7.12). The reaction with acrylonitrile gave 4-phenylbutanenitrile in 14% yield together with cis- and tra 5-4-phenyl-2-butenenitriles, 4-cyano-6-phenylhexanenitrile, and 2-ben-zyl-4-phenylbutanenitrile (Equation 7.13). The results suggest the presence of a benzylnickel(II) chloride complex (1), which could have been formed by the oxidative addition of benzyl chloride to the metallic nickel (Scheme 7.7). The complex (I) would then be expected to add to the electron-deficient olefins, affording the addition product (111) via intermediate complex (IV). The formation of cis- and tra s-4-phenyl-2-butenenitrile (V) is reasonably explained by the reductive elimination of nickel hydride from intermediate (IV), which is analogous to the substitution reaction of olefins with alkylpalladium compound [158] and to the addition-elimination reaction of bis(triphenylphosphine) phenylnickel(II) bromide with methyl acrylate to yield methyl cinnamate [130]. Furthermore, intermediate (IV) seems to add another molecule of acrylonitrile to give the 1 2 adduct 4-cyano-6-phenylhexanenitrile (VI). 2-Benzyl-4-phenylbutanenitrile (VIII) would be formed by the metathesis of complex IV and the benzylnickel chloride (I). 

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