Sulfoxide Oxidations

Benzenediamine (129) gave 2-phenylquinoxaline (132) [BzCH2SOMe or BzCH(SOMe)2, PhH, AcOH, reflux, 2 h 35% after separation from another product aerial or sulfoxide oxidation required with the first reagent). 

The aldehyde 38 was obtained from 35, by way of 36 and 37, by the carbodiimide—dimethyl sulfoxide oxidation procedure52 in the presence of 3-(3-dimethylaminopropyl)-l-ethylcarbodiimide hydrochloride (EDAC)53 and dichloroacetic acid. It was isolated in the form of its crystalline 1,3-diphenylimidazolidine derivative (39) by trapping the freshly prepared aldehyde 38 with N,N -diphen-ylethylenediamine. (This reagent was developed by Wanzlick and Lochel54 for the selective derivatization of aldehydes, and has been exploited for the isolation of nucleoside 5 -aldehydes55 and other aldehydo derivatives of carbohydrates by Moffatt and coworkers.52(b))... 

Sulfides Sulfoxides Oxidizing agent Experimental conditions Isolated yield (%) Reference... 

Chlorpromazine can be oxidized by aqueous bromine solutions, and after removal of any unconsumed bromine by sparging the solution with nitrogen, the sulfoxide oxidation product is determined by polarography... 

The mechanism of these dimethyl sulfoxide oxidations is probably as follows 331... 

Dimethyl sulfoxide oxidations W. W. Epstein, F. W. Sweat, Chemical Reviews 1967, 67, 247 An improved reagent, based on the general idea associated with DMSO-based oxidations has been reported ... 

Substituent Group Effect During Sulfide —> Sulfoxide Oxidation... 

Crystalline l,2-0-isopropylidene-a-D-g/Mco-hexodialdo-l,4 6,3-difuranose (179) has been prepared381 via dimethyl sulfoxide oxidation of 178, and by chromic acid oxidation of 1,2-O-isopropylidene-a-D-glucofuranose.382... 

D. M. Mackie and A. S. Perlin, Synthesis of u,/i-unsaturated, carbonyl sugar derivatives by methyl sulfoxide oxidation and elimination, Carbohydr. Res., 24 (1972) 67-85. 

Federsel, H.-J., Larsson, M. An Innovative Asymmetric Sulfoxide Oxidation The Process Development History behind the Antiulcer Agent Esomeprazole. In Asymmetric Catalysis on Industrial Scale, Blaser, H.-U., Schmidt, E Eds., Wiley-VCH Weinheim, 2004, p. 413. 

Sulfur-lithium exchange is easier and has much greater potential (much of it still unrealised) when the sulfur is at the sulfoxide oxidation level. It has long been known that organolithiums, like Grignard reagents, will attack a sulfoxide, displacing with inversion at sulfur the substituent best able to support an anion. The reaction has been commonly used to form sulfoxides with defined stereochemistry 152157... 

The hydridorhodium(III) species HRh(NH3)52+ and HRh(CN)4-(H20)2 are known to react with 02 to give hydroperoxide species, Rh—OOH (102, 103, 104) the sulfoxide oxidation via such an intermediate could be accommodated by several mechanisms akin to those discussed already for olefinic substrates (cf. Reactions 17 and 18). The oxidation also could occur via liberated hydrogen peroxide, which oxidizes sulfoxide to sulfone and can be formed by treatment of Rh—OOH species with acid (104). Such a mechanism would amount to a novel catalytic conversion of H2/02 mixtures to in situ H202. The part of the enzymatic cycle of P 450 that utilizes 02 and two electrons (from a hydride source) can be bypassed by using hydrogen peroxide (16, 18). 

Providing the two groups attached to sulfur are different, a sulfoxide is chiral at the sulfur atom. There are two important ways of making sulfoxides as single enantiomers, both asymmetric versions of reactions otherwise used to make racemic sulfoxides oxidation and nucleophilic substitution at sulfur. 

Dehydrogenation A-Demethylation Hydroxylation Epoxidation Sulfoxidation Oxidations Acetaminophen, benzidine, DES, epinephrine Dimethylaniline, benzphetamine, aminocarb Benzo[a]pyrene, 2-aminofluorene, phenylbutazone 7,8-Dihydrobenzo[a]pyrene Methylphenylsulfide FANFT, ANFT, bilirubin Esterases and Amidases Paraoxon, dimethoate, phenyl acetate Epoxide Hydrolase Benzo(a)pyrene epoxide, styrene oxide DDT-Dehydrochlorinase p,p- DDT Glutathione Reductase Disulfiram... 

The advantage of using peracids is their ability to oxidize sulfoxides selectively over sulfides at high pH using the nucleophilic anion (Figure 3.95) since sulfoxide oxidation is nucleophilic, whereas sulfide oxidation is electrophilic. This behaviour is due to the formation of peroxidic intermediates by the addition of peroxy anion to the sulfoxide.378... 

Figure 11.5 Structure and synthesis of the polyoxometalate (POMs) library L4 and POM-catalyzed sulfide-sulfoxide oxidation of 11.4.

The sulfur trioxide- dine activated dimethyl sulfoxide oxidation was also a key step in an excellent synthesis of die Prelog- jerassi lactonic acid, being highly recommended as the best method to avoid epimeiization of the C-2 center in the aldehyde (33). ... 

One class of compounds that does not react particularly well in activated dimethyl sulfoxide oxidations, however, b the alkynic alcdiols, and only a few successful examples are known. e.g. (36) and... 

Activattd dimethyl sulfoxide oxidations have been fairly well used in the synthesis of monoterpenes, as seen in the oxidation to an aldehyde of the alcohols (40), en route to loganin aglycone, and (41), a precursor in a synthesis of specionin (equation 16). ... 

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