Radical debromination

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

One-electron reduction of organic halides is convenient for generating radicals. gem-Dibromocyclopropancs are reduced by such a system [77]. Using an excess of MoH2Cp2, stereoselective debromination is successful, possibly because of... 

Viologen salts act as one-electron phase-transfer agents and, in conjunction with sodium dithionite which regenerates the bipyridinium radical cation, they have been used for the debromination of 1,2-dibromoalkanes to yield alkenes in variable yields [13-15]. Nitroarenes are reduced to anilines in high yield (>90%) under similar conditions [16], whereas conjugated nitroalkenes are converted into the oximes of the saturated ketones [17] saturated aliphatic nitro compounds are not reduced by this process. 

A good diastereocontrol is obtained for the debromination of Reaction (4.14) and it is attributed to the bulky reducing agent, which approaches the radical intermediate from the less hindered face anti to the two vicinal substituents [35]. 

Pinson and Saveant 1978, Swartz and Stenzel 1984). On electrochemical initiation (Hg cathode), 4-bromobenzophenone gives rise to 4-(phenylthio)benzophenone in the 80% yield, whereas bromoben-zene yields diphenyldisulfide with the yield of only 10% and unsubstituted benzene with the yield of more than 95%. In the bromobenzene case, this means that the substitution is a minor reaction, whereas the main ronte is ordinary debromination. According to Swartz and Stenzel (1984), the substrate anion-radicals are initially formed in the preelectrode space. Stability of these anion-radicals are different. The less stable anion-radicals of bromobenzene do not have enough time to go into the catholyte pool. They give rise to the phenyl radicals in the vicinity of the cathode. The phenyl radicals are instantly reduced into the phenyl anions. They tear protons from the solvent and yield benzene. 

Swartz and Stenzel (1984) proposed an approach to widen the applicability of the cathode initiation of the nucleophilic substitution, by using a catalyst to facilitate one-electron transfer. Thus, in the presence of PhCN, the cathode-initiated reaction between PhBr and Bu4NSPh leads to diphe-nydisulfide in such a manner that the yield increases from 10 to 70%. Benzonitrile captures an electron and diffuses into the pool where it meets bromobenzene. The latter is converted into the anion-radical. The next reaction consists of the generation of the phenyl radical, with the elimination of the bromide ion. Since generation of the phenyl radical takes place far from the electrode, this radical is attacked with the anion of thiophenol faster than it is reduced to the phenyl anion. As a result, instead of debromination, substitution develops in its chain variant. In other words, the problem is to choose a catalyst such that it would be reduced more easily than a substrate. Of course, the catalyst anion-radical should not decay spontaneously in a solution. 

The photochemistry of Eosin under both reductive and oxidative conditions has been studied by several groups [145-151], Photoreduction by amines such as tribenzylamine (R = CH2, R" = ) produces two leuco analogues, the dihydro derivative, and the cross-coupled product formed from the amine radical and the dye radical anion (2) [152], In addition, debromination of Eosin is reported during photobleaching with amines and phenols. The reader however is referred to the extensive studies of Rose Bengal dehalogenation by Paczkowski and Neckers [153]. Radiolysis of Eosin in methanol shows that debromination is a consequence of the photochemical decomposition of semireduced Eosin [154],... 

The lifetimes of some of these carbanions may be limited by their dissociation to a phenyl radical and a stable anion. This pattern of reaction has been demonstrated in the -induced quantitative deiodina-tion of the iodobenzoic acids, as well as in the debromination of p-bromo-phenol (Anbar et al., 1967). 

Fused tetracyclic biaryl-2-azetidinones have been prepared by the radical cyclization of aryl /3-lactam-tethered haloarenes. Azetidin-2-one 504, having an extra radical acceptor on C-3, underwent radical cyclization with tributyltin hydride to give the biaryl-2-azetidinone 505 in a low yield, with debrominated 3-phcnoxyA-phcnyl-l -(/ -methoxy-phenyl)-2-azetidinone as the main product (60% yield) (Equation 82). But when the azetidinones 506 (Rz = R6 = H) bearing an extra link (O) on the radical precursor at C-3 or N-l of the /3-lactam ring were treated with tributyltin hydride, the expected cyclization products 507 were obtained. If azetidinones 506 (Rz = OMe, or Me R6 = H, OMe, or Me) were treated in the same way then the tetracyclic azetidinones 508 were produced (Equation 83) <2005T7894>. 

Stereoselective synthesis of (+ )-botryodiplodin was carried out by a radical cyclization of dibromoacetal (203) containing an allene group, with Bu3SnH initiated by Et3B, through the 5-exo-trig cyclization, and the subsequent debromination with bulky... 

Selective radical bromination of the p-methyl group by elemental bromine is performed in solution either thermally, photolytically, or in the presence of radical initiators. The reaction does not lead to any change in molar mass or distribution, and the only potential side reaction, which has to be controlled by adjusting the reaction conditions, is debromination between two p-bromobenzyl moieties. Under similar conditions radical chlorination leads to substitution on the benzylic site as well as on the methylene and methyl groups of isobutene units, with changes in molar mass. 

Aryl-substituted vic-dibromides undergo debromination to produce the corresponding E-alkenes when treated with indium metal in MeOH. Since debromination occurs by the usual trans-elimination, meso/erythro- and d,Z-/f/zreo-vic-dibromides would give trans- or cis-alkenes, respectively, as shown in Scheme 4.6. It is thus suggested that in this case the reaction occurs via a common relatively stable radical or anion intermediate, which directly collapses to -alkene. 

Indium is reported to be an efficient catalyst for the debromination processes of vic-dibromides. An illustration of the utility of this method is in the debromination of aryl-substituted vic-dibromides to produce the corresponding (E)-alkenes with indium metal in MeOH. In general, the reaction proceeds via a common, relatively stable radical intermediate, collapse of which leads directly to the (E)-alkenes, and methanol is found to be the best solvent for this reaction. ... 

In the electrochemical reduction of 5-bromo-l-methyl-4-nitroimidazole some cleavage of the C—Br bond is evident giving rise to the debrominated product (79JGU1877). Imidazole itself is not reducible cathodically in aqueous media, but electrons have been attached to imidazole and histidine in aqueous solution the rate of oxidation depends on pH. Protonated or quaternized imidazoles form the neutral conjugate acids of the true anion radical, and a number of anion radicals have been made from nitroimidazoles under various radiolytic conditions (79AHC(25)205). The electrochemical reduction of 2-cyanobenzimidazole 3-oxide gives sequentially 2-cyanobenzimidazole and 2-aminomethylbenzimidazole (80ZC263). 

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