Benzylic nickel halides preparation

The development of the Grignard-type addition to carbonyl compounds mediated by transition metals would be of interest as the compatibility with a variety of functionality would be expected under the reaction conditions employed. One example has been reported on the addition of allyl halides to aldehydes in the presence of cobalt or nickel metal however, yields were low (up to 22%). Benzylic nickel halides prepared in situ by the oxidative addition of benzyl halides to metallic nickel were found to add to benzil and give the corresponding 3-hydroxyketones in high yields(46). The reaction appears to be quite general and will tolerate a wide range of functionality. 

In spite of the usefulness of these complexes, it is generally not possible to cause the satisfactory reaction with transition metals in the metallic state [86] under mild conditions due to their poor reactivity. We have reported that activated metallic nickel, prepared by the reduction of nickel halide with lithium, underwent oxidative addition of benzylic halides to give homocoupled products [45]. We reported that carbonylation of the oxidative adducts of benzylic halides to the nickel proceeded smoothly to afford symmetrical 1,3-diarylpro-pan-2-ones in moderate yields, in which the carbonyl groups of alkyl oxalyl chlorides served as a source of carbon monoxide [43] see Equation 7.5. 

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. 

Metallic nickel was easily prepared by stirring a mixture of nickel halide and lithium metal (2.3 equiv) with naphthalene (0.1 equiv) as an electron carrier at room temperature for 12 h in DME (glyme) (Equation 7.9). The resulting black powders which slowly setded in a colorless solution after stirring was stopped were used for the reductive homocoupling reaction of benzylic halides (Equation 7.10). 

The homo-coupling reaction of benzylic halides by metallic nickel proceeded at room temperature. 1,2-Diarylethanes having a variety of functional groups could be easily prepared by this method in good to high yields. 

Benzyl cyanide, prepared according to Org. Syn. Coll. Vol. 1, 1941, 107, should be distilled from Raney nickel. Minute traces of halide ha - a strong poisoning effect on the catalyst. If the reduction does not occur within an hour, the contents of the bomb should be removed and filtered. New catalyst is then added and the process is repeated. 

Cross coupling between an aryl halide and an activated alkyl halide, catalysed by the nickel system, is achieved by controlling the rate of addition of the alkyl halide to the reaction mixture. When the aryl halide is present in excess, it reacts preferentially with the Ni(o) intermediate whereas the Ni(l) intermediate reacts more rapidly with an activated alkyl halide. Thus continuous slow addition of the alkyl halide to the electrochemical cell already charged with the aryl halide ensures that the alkyl-aryl coupled compound becomes the major product. Activated alkyl halides include benzyl chloride, a-chloroketones, a-chloroesters and amides, a-chloro-nitriles and vinyl chlorides [202, 203, 204], Asymmetric induction during the coupling step occurs with over 90 % distereomeric excess from reactions with amides such as 62, derived from enantiomerically pure (-)-ephedrine, even when 62 is a mixture of diastereoisomcrs prepared from a racemic a-chloroacid. Metiha-nolysis of the amide product affords the chiral ester 63 and chiral ephedrine is recoverable [205]. 

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 . ... 

Apart from their behaviour as ligands in metal catalyst systems, studies of the reactivity of phosphites towards a wide variety of other substrates have attracted attention. New aspects and applications of the classical Michaelis-Arbuzov reaction and its variants continue to appear. Evidence of the thermal disproportionation of methyltriaryloxyphosphonium halides formed in the reactions of triarylphosphites with alkyl halides, together with the formation of P-O-P intermediates, has been reported. The Michaelis-Arbuzov reaction has been used in the synthesis of phosphonate-based styrene-divinylbenzene resins and polyphosphonated chelation therapy ligands.Treatment of electron-rich benzylic alcohols dissolved in triethylphosphite with one equivalent of iodine affords a low-temperature one-pot route to the related benzylic phosphonates, compounds which are otherwise difficult to prepare. Upper-rim chloromethylated thiacalix[4]arenes have also been shown to undergo phosphonation on treatment with a phosphite ester in chloroform at room temperature. The nickel(II)-catalysed reaction of aryl halides with phosphite esters in high boiling solvents, e.g., diphenyl ether, (the Tavs reaction), has also... 

Vanhoye and coworkers [402] synthesized aldehydes by using the electrogenerated radical anion of iron pentacarbonyl to reduce iodoethane and benzyl bromide in the presence of carbon monoxide. Esters can be prepared catalytically from alkyl halides and alcohols in the presence of iron pentacarbonyl [403]. Yoshida and coworkers reduced mixtures of organic halides and iron pentacarbonyl and then introduced an electrophile to obtain carbonyl compounds [404] and converted alkyl halides into aldehydes by using iron pentacarbonyl as a catalyst [405,406]. Finally, a review by Torii [407] provides references to additional papers that deal with catalytic processes involving complexes of nickel, cobalt, iron, palladium, rhodium, platinum, chromium, molybdenum, tungsten, manganese, rhenium, tin, lead, zinc, mercury, and titanium. 

Rieke and coworkers have found that a special type of activated metallic nickel, available through reduction of nickel(II) iodide with lithium metal, suffers oxidative addition of benzylic and allylic halides. The resulting nickel(Il) complexes readily undergo cross-coupling with acid chlorides to form ketones. Once again it was difficult to obtain, y-unsaturated ketones from this method. Moderate to good yields of simple ketones may be prepared by this method. 

Unsymmetrical biaryh and diarylmethanes. Negishi et al have used a nickel-(0) complex or a palladium(0) complex as catalyst for the cross-coupling of aryl-or benzylzinc halides with aryl halides at room temperature to form biaryls or diarylmethanes. The zinc derivatives are prepared by reaction of aryl- or benzyl-lithium with zinc chloride or bromide. 

Silyl and stannyl hydrides effect high yield reduction of aryl diazonium salts, and are compatible with a wider range of solvents than is HaP02. NaH prepared situ has been found to be much more active than the commercial product. Using the more active NaH, hydrogenolysis of benzylic halides is possible. Sodium borohydride has been reported to reduce nitriles to amines if Raney nickel is used as catalyst. 

Preparation of 3-Aryl-2-hydroxy-1 -propane by Nickel-Mediated Addition of Benzylic Halides to... 

We reported that smooth oxidative addition of organic halides such as aryl, benzyl, and allyl halides to metallic nickel proceeded to afford organonickel halides under mild conditions, which yielded homocoupled products [11, 41] or ketones by the reaction with acid chlorides [42] or alkyl oxalyl chlorides [43]. We describe here a new method for the preparation of 3-aryl-2-hydroxy-l-propanones (4) in good yield by the Grignard-type addition of benzyl halides to 1,2-diketones mediated by metallic nickel under neutral conditions [44]. 

Preparation of 3-Arylpropanenitriles by Nickel-Mediated Reaction of Benzylic Halides with Haloacetonitriles... 

Table 7.5 3-Arylpropanenitriles (3) prepared by the reaction of benzyl halides (1) with bromoacetonitrile (2 = nickel). ... 

Table 7.7 Preparation of symmetrical l,3-diarylpropan-2-ones by the reaction of benzylic halides with alkyl oxalyl chlorides in the presence of metallic nickel."... 

The results of the reaction of benzyl and substituted benzyl halides with metallic nickel powders are summarized in Table 7.13. Benzyl chloride reacted at room temperature with metallic nickel prepared from nickel chloride to give a mixture of the coupled product bibenzyl (40%) and the reduction product toluene (60%). However, the coupled product was found to be formed mainly when the reaction was run at 70°C and when the nickel powders used were prepared from nickel iodide. Under these conditions, a yield of 86% bibenzyl was attained. The fact that iodide ion present in the system facilitates the homocoupling reaction may be ascribed to the chlorine-iodine exchange during the reaction [148]. Higher reaction temperatures such as 70°C may also accelerate the exchange reaction. 

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