Benzyl and Aryl Halides

Dehalogenation of benzyl chloride over Raney Ni may result in the formation of either toluene or dibenzyl (1,2-diphenylethane).229 For example, heating 10 g of benzyl chloride with 20 g Raney Ni in 100 ml of boiling methanol for 4 h gave 0.6 g dibenzyl and 2.6 g toluene. When the amount of Raney Ni was reduced to 10 g, the amount of dibenzyl increased to 1.1 g, while with 40 g Ni the amount of toluene increased to 5 g (70%). Under the same conditions, but in the presence of 1 equiv of potassium hy- 

TABLE 13.9 Effects of Media on the Rate of Hydrogenolysis of Benzyl Chloride over Pd-C, Pt-C, and Rh-C Catalysts 6 

6Benzyl chloride (4.5 ml) was hydrogenated over 0.5 g of 5% metal-C in 100 ml solvent at room temperature and atmospheric pressure. 

Bromobenzene is hydrogenolyzed in a much greater rate than chlorobenzene over Pd-C in methanol. The rates are further increased by added potassium acetate for both bromo- and chlorobenzenes.196 In one patent, sodium phosphate was used as an effective base in the dechlorination of 4,6-dichloro-2-nitroresorcinol to 2-aminoresorcinol over Pd-C.234 

The halogens on aromatic rings may be activated by an electron-withdrawing group located at the ortho and para positions. / Fluorobenzoic acid, as its sodium salt in an aqueous solution, was hydrogenolyzed to give benzoic acid and then more slowly converted to cyclohexanecarboxylic acid over platinum catalyst.235 With Raney Ni or Raney Co alloy and alkali, it was also defluorinated.231 

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Organocadmium compounds can be prepared from Grignard reagents or organo-lithium compounds by reaction with Cd(II) salts.180 They can also be prepared directly from alkyl, benzyl, and aryl halides by reaction with highly reactive cadmium metal generated by reduction of Cd(II) salts.181... 

Hydroxycarbonylation and alkoxycarbonylation of alkenes catalyzed by metal catalyst have been studied for the synthesis of acids, esters, and related derivatives. Palladium systems in particular have been popular and their use in hydroxycarbonylation and alkoxycarbonylation reactions has been reviewed.625,626 The catalysts were mainly designed for the carbonylation of alkenes in the presence of alcohols in order to prepare carboxylic esters, but they also work well for synthesizing carboxylic acids or anhydrides.137 627 They have also been used as catalysts in many other carbonyl-based processes that are of interest to industry. The hydroxycarbonylation of butadiene, the dicarboxylation of alkenes, the carbonylation of alkenes, the carbonylation of benzyl- and aryl-halide compounds, and oxidative carbonylations have been reviewed.6 8 The Pd-catalyzed hydroxycarbonylation of alkenes has attracted considerable interest in recent years as a way of obtaining carboxylic acids. In general, in acidic media, palladium salts in the presence of mono- or bidentate phosphines afford a mixture of linear and branched acids (see Scheme 9). 

Recently, the electrocarboxylations of benzyl and aryl halides and perfluoroalkyl-halides [39] in supercritical mixture or in supercritical carbon dioxide (scC02) and of aryl and benzyl halides in microemulsion [40], were also investigated in order to exploit the possible effect of the use of these solvents on the selectivity of the... 

In 1979 the reaction of benzyl and aryl halides was reported with mechanistic discussions [8, 9]. The first palladium-catalyzed carbonylative coupling of organic halides with organotin compounds was reported by Tanaka in the same year (Scheme 4) [10,11]. 

Oxidative addition [1, 38] of 1-alkenyl, 1-alkynyl, allyl, benzyl, and aryl halides to a palladium(O) complex affords a stable trans-o-p al 1 adi u m( 11) complex (11). The reaction proceeds with complete retention of configuration for alkenyl halides and with inversion for allylic and benzylic halides. Alkyl halides having /5-hydrogens are rarely useful because the oxidative addition step is very slow and may compete with /5-hydride elimination from the <7-organopalladium(II) species. However, it has been recendy shown that iodoalkanes undergo the cross-coupling reaction with organoboron compounds (Section 2.4.5). 

The first discussed mechanism was for the reaction with benzylic and aryl halides in 1979 [8],[9] shown in other protocols, the three-step catalytic cycle is widely accepted, that is, oxidative addition, transmetallation, and reductive elimination (Scheme 5). 

This synthesis of carboxylic acids is applicable to primary, secondary, tertiary, allyl, benzyl, and aryl halides, provided they have no groups incompatible with a Grignard reaction (see Section 12.8B) ... 

Aryl, Alkenyl, Benzyl, and Alkynyl Halides, and Their Pseudo-Halides... 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Tnfluorometltylation of aryl, alkenyl, and alkyl halides can be accomplished by heating methyl fluorosulfonyldifluoroacetate and the appropriate halide precursor with copper(I) iodide at 60-80 °C in DMF [27 7] (equation 145). Similar trifluoromethylations of aryl, benzyl, and vinyl halides can be carried out with fluorosulfonyldifluoromethyl iodide and copper metal in DMF at 60-80 °C [2 75] (equation 146). 

Alkylation reactions are subject to the same constraints that affect all Sn2 reactions (Section 11.3). Thus, the leaving group X in the alkylating agent R—X can be chloride, bromide, iodide, or tosylate. The alkyl group R should be primary or methyl, and preferably should be allylic or benzylic. Secondary halides react poorly, and tertiary halides don t react at all because a competing E2 elimination of HX occurs instead. Vinylic and aryl halides are also unreactive because backside approach is sterically prevented. 

Alkenylboranes (R2C=CHBZ2 Z — various groups) couple in high yields with vinylic, alkynyl, aryl, benzylic, and allylic halides in the presence of tetra-kis(triphenylphosphine)palladium, Pd(PPh3)4, and a base to give R C CHR. 9-Alkyl-9-BBN compounds (p. 1013) also couple with vinylic and aryl halides " as well as with a-halo ketones, nitriles, and esters.Aryl halides couple with ArB(IR2 ) species with a palladium catalyst. ... 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

The method is quite useful for particularly active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, " and to activated alkenes such as acrylonitrile. The latter is a Michael type reaction (p. 976) with respect to the alkene. 

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