Halides reductive dehalogenation

An important synthetic application of this reaction is in dehalogenation of dichloro- and dibromocyclopropanes. The dihalocyclopropanes are accessible via carbene addition reactions (see Section 10.2.3). Reductive dehalogenation can also be used to introduce deuterium at a specific site. The mechanism of the reaction involves electron transfer to form a radical anion, which then fragments with loss of a halide ion. The resulting radical is reduced to a carbanion by a second electron transfer and subsequently protonated. 

An alternative route to sulphones utilizes the reaction of the appropriate activated halide with sodium dithionite or sodium hydroxymethanesulphinite [6], This procedure is limited to the preparation of symmetrical dialkyl sulphones and, although as a one-step reaction from the alkyl halide it is superior to the two-step oxidative route from the dialkyl sulphides, the overall yields tend to be moderately low (the best yield of 62% for dibenzyl sulphoxide using sodium dithionite is obtained after 20 hours at 120°C). The mechanism proposed for the reaction of sodium hydroxymethanesulphinite is shown in Scheme 4.20. The reaction is promoted by the addition of base and the best yield is obtained using Aliquat in the presence of potassium carbonate. It is noteworthy, however, that a comparable yield can be obtained in the absence of the catalyst. The reaction of phenacyl halides with sodium hydroxy-methane sulphinite leads to reductive dehalogenation [7]. 

In a similar type of reaction, polymer-supported hydridoiron tetracarbonyl anion reacts with simple non-benzylic aliphatic bromides and iodides to produce aldehydes (Table 8.15), presumably through the intermediate formation of RCOFeH(CO)3, which undergoes reductive extrusion of the aldehydes [3], In contrast, benzylic halides and a-halocarbonyl compounds are reductively dehalogenated by the HFe(CO)4 anion (see Chapter 11). 

The yields of ketones, isolated from the reductive debromination of a-bromo-ketones by dicobalt octacarbonyl under basic phase-transfer conditions are good (Table 11.13), but are improved (>95%) by the use of stoichiometric amounts of the quaternary ammonium catalyst. Somewhat unexpectedly, in the case of the reductive dehalogenation of secondary benzylic halides, the yields of the coupled alkanes are... 

In a manner analogous to the formation of the other hydridometal complexes, the tricarbonylhydridovanadate anion is easily produced from r)5-cyclopentadienyl-vanadiumtetracarbonyl under basic phase-transfer catalytic conditions and it has been used in the reduction of nitro compounds and the reductive dehalogenation of a wide range of halides [ 12]. 

The cathodic substitution of halides has been applied in the synthesis of antiinflammatory agents. Arylpropionic acids are formed by reductive dehalogenation of the corresponding benzylic halides in the presence of carbon dioxide as electrophile [22] ... 

Lithium triethylborohydride (Super-Hydride) is a much more powerful reducing agent than lithium aluminium hydride. It is useful for the reductive dehalogenation of alkyl halides, but unlike lithium aluminium hydride does not affect aryl halides. It is available as solution in tetrahydrofuran in sealed containers under nitrogen. The solutions are flammable and moisture sensitive and should be handled with the same precautions as are taken with other organometallic reagents (see Section 4.2.47, p. 442). 

Photolysis of 2-bromo-4,4-dimethyl-2-cyclohexenone only affords reduction, even in a nucleophilic medium343,344. Apparently, this substrate is structurally not suitable to form a vinyl cation. Formation of vinyl radical-derived products is also the main process for all vinylic halides, if their irradiation is performed in an apolar medium. Such photochemical reductive dehalogenation and especially dechlorination reactions have been extensively studied in the past, not in the least because of their importance as abiotic transformation of persistent polychlorinated environmental pollutants. Examples are the cyclodiene insecticides aldrin and dieldrin, which contain a vicinal dichloroethene chromophore. In recent... 

Magdesieva, T.V., Graczyk, M., Vallat, A., Nikitin, O.M., Demyanov, P.I., Butin, K.P. and Vorotyntsev, M.A. (2006) Electrochemically reduced titanocene dichloride as a catalyst of reductive dehalogenation of organic halides. Electrochim. Acta 52, 1265-1280. 

Decarboxylation of benzoates in the presence of an aryl halide (20, 33, 211) affords the biphenyl substitution products in yields of up to 50% if the medium is an iV-heteroaromatic solvent. The solvent must be dry to avoid reductive dehalogenation (54). If the solvent is dry diglyme or xylene, an ester can be isolated in high yield (54). 

Red-Al [sodium bis(2-methoxyethoxy)aluminium hydride] reduces aliphatic halides and aromatic halides to hydrocarbons. Reductive dehalogenation of alkyl halides is most commonly carried out with super hydride. Epoxide ring can also be opened by super hydride. 

The reduction of saturated alkyl halides to alkanes, as represented in equation (1), is the most fundamental reaction of reductive dehalogenations of organic halides. The importance of these reductions has stimulated considerable investigation, and a number of successful approaches have been reported hitherto. Numerous reducing agents or reagent systems are available and many of them have been applied to practical organic synthesis with notable success. 

In 1980, Finder presented an excellent review dealing with the hydrogenolysis of organic halides. Many other reviews are also available, although they are not devoted to reductive dehalogenation but deal with it as part of the broader topic of reduction. 

The order of ease of reductive dehalogenation of organic halides in the same type of structural environment is I > Br > Cl F. This order is parallel with the dissociation energy of carbon-halogen bonds (HsC—I 234 kJ mol- H3C—Br 293 kJ mol" H3C—Cl 351 kJ mol- H3C—F 452 kJ moL ) and is generally observed in the reduction of alkyl halides. Consequently, selective reduction of di- or polyhalides containing different halogen atoms is possible. Fluorides are often removed only with difficulty and examples of such reductions are comparatively limited. 

A classical method using Na- or Li-liquid ammonia (Birch reduction conditions) is effective for reductive dehalogenations of aryl and vinylic halides, but it is not always successfully applied to alkyl halides, although cyclopropyl halides and bridgehead halogens are exceptions.Under such conditions, the reactions are often accompanied by side reactions, such as elimination, the Wurtz coupling reaction, cyclization and reduction of carbonyl compounds. An example, a synthesis of pentaprismane (1), is shown in Scheme 4. ... 

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