Bromide-mediated oxidations

The beauty of bromide-mediated oxidations is that they combine mechanistic complexity with practical simplicity and, hence, utility. They involve an intricate array of electron transfer steps in which bromine atoms function as go-betweens in transfering the oxidizing power of peroxidic intermediates, via redox metal ions, to the substrate. Because the finer mechanistic details of these elegant processes have often not been fully appreciated we feel that their full synthetic potential has not yet been realized. Hence, we envision further practical applications in the future. 

The process was shown to be more efficient when performed in the presence of some bromide salts whose oxidation allows lowering of the working potential and favors the S—S bond scission. Bromide mediated oxidation of bis(2-cyclopent-l-enylethane) and bis (2 -cyclohex-1 -enylethane) disulfide in AN/Et4NCl04/Et4NBr [130] undergoes the S—S bond cleavage followed by an intramolecular attack of the sulfenium cation on the double bond to give [3.3.0] and [4.4.0] bicyclic products. The anion Br also serves in the process as an... 

It is shown [79] that compounds VIII-X are oxidized much more easily in the presence of trace amounts of bromide ions when compared with their corresponding exo isomers, with X = COJ, CH2OH, CMe20H, Y = H. Controlled-potential electrolyses of VIII-X yield mixtures of diastereomeric sulfoxides (for VIII) or of diastereomeric alkoxysulfonium salts (for IX and X). These results are explained in terms of a neighboring carboxylate or alcohol participation in the bromide mediated oxidation of the thioethers. 

Transformation of 4-methylpyrazoles into 4-carboxylic acids takes place readily by cobalt-manganese bromide mediated oxidation <91CL585>. Begtrup <92JCS(P1)2555> has developed a method to activate methyl groups at positions 3 and 5 using 2-alkoxy-pyrazohum derivatives (181) in this way pyrazoles (182) were prepared (X = D, I, OMe). 

A one-pot three-component synthesis of a-iminonitriles 866 via an IBX/tetrabutylammonium bromide-mediated oxidative Strecker reaction has been developed (Scheme 3.346) [1183]. This methodology was employed in a two-step synthesis of indolizidines via a microwave-assisted intramolecular cycloaddition of a-iminonitriles. 

Using this reaction, 1-cystine was converted to 1-cysteic acid the process gives better yields when mediated by bromide ion oxidation [118]. 

In the improved synthesis of Ifetroban described above, environmental concerns due to special handling of copper bromide waste and hazards associated with hexa-methylene tetramine (HMT) on manufacturing scale led to further perfection of the synthesis. Mechanistic considerations suggested that an oxidized form of aminoamide B (Scheme 4) would eliminate the necessity for a late-stage copper-mediated oxidation. This was indeed accomplished. The cyclization-elimination sequence was initiated by a Lewis acid and completed by base-mediated elimination to afford the Ifetroban penultimate. In addition to eliminating the need for copper bromide and HMT, this modification helped to reduce the cost of the product by an additional 15%. 

A scant look at the facts might suggest that the selective oxidation of primary alcohols in TEMPO-mediated oxidations can be explained solely on steric grounds. Things are not so simple, as it was found8 that the primary oxidants, that is oxoammonium salts, when used stoichiometrically, react quicker with primary alcohols when present as oxoammonium chlorides, while the reverse selectivity, that is selective oxidation of secondary alcohols, is observed when oxoammonium bromides are employed. 

P. L. Bragd, A. C. Besemer, and H. van Bekkum, Bromide-free TEMPO-mediated oxidation of primary alcohol groups in starch and methyl a-D-glucopyranoside, Carbohydr. Res., 328 (2000) 355-363. 

In the presence of bromide the oxidation is thought to be mediated by the very reactive bromine atoms, without any direct interaction between cobalt(III) and the methylbenzene (Equations 3 X is a generic anionic ligand) ... 

One of the earliest synthetic reactions in which the halide anion was used as a mediator is the anodic methoxylation of fiiran in the presence of 0.05 equiv. of amnoonium bromide, though the reaction has not been termed a mediated oxidation (equation 64)7 ... 

Attempts to obtain 1-cysteic acid by direct electrochemical oxidation of 1-cystine led to low material yields and mixtures of products [52], but bromide-mediated electrolyses in a divided cell afford the expected product in high yield, as in Eq. (22). 

A convenient desulfanylation of Michael adducts of ethanethiol with a, j6-unsatu-rated esters, ketones, and nitriles occurs under neutral conditions by a bromide ion-mediated oxidation, as in Eq. (63) [118]. If MeS, r-BuS, and PhS are substituted for EtS, the effect on the yield is relatively small. 

In TEMPO-mediated oxidations, bromide ions are key to the efficient catalytic cycle (Figure 9.10) [29, 30]. Rychnovsky found thatTEMPO-catalyzed oxidation of alcohols using m-CPBA was also dependent on bromide ions for rapid reaction [31]. Any compounds that sequester bromide ions in these catalyzed reactions should be avoided. 

As described at the end of the last section, we came upon the study of metal oxide nanoparticles in aqueous solution accidentally. Our only earlier experience with this class of nanoparticles, although in organic solvents such as THF, was the investigation of the controlled 02-mediated oxidation of tetraalkylammonium bromide stabilized cobalt colloids prepared size-selectively by the electrochemical method (Fig. 8.5) [53]. 

The sodium periodate-mediated oxidation of alkali halides is a useful method to accomplish the halogenation of aromatic compounds. Accordingly, NaCl is successfully employed as a chlorine source for the chlorination of various aromatic compounds, although mixtures of regioisomers are sometimes obtained on the other hand, the related sodium periodate-mediated bromina-tion reaction, which uses lithium bromide or sodium bromide as halogen source, affords the expected brominated products in a regioselective fashion (eq 33). ... 

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