Dimethyl sulfoxide, oxidation

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))... 

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 ... 

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... 

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). ... 

The above discussion highlights the great synthetic utility of activated dimethyl sulfoxide oxidations in organic chemistry. The enormous amount of effort put into developing these procedures has resulted in a clear picture of their relative value, so enabling one to easily assess the method of chmce for a particular oxidation. The pc ularity of the Swem oxidation reflects the very real advantages that it offers in terms of the mild conditiotts arid hi yields. However, there are many instances where alternative activators of dimethyl sulfoxide are better and it is wise to assess these in any synthetic scheme. 

Thus activated dimethyl sulfoxide oxidations are now well established as standard synthetic methods and ate familiar to all organic chemists, and will continue into the future as new variations are developed. 

To appreciate this important reaction requires a mechanistic understanding of how dimethyl sulfoxide can be activated for use as an oxidant The following discussion therefore begins with the general mechanism of the reaction, followed by a description of the use of the more important activation methods, many of which are complementary. A description of the process from the viewpoint of the substrate then follows, emphasizing the advantages of using the activate dimethyl sulfoxide oxidation method. Earlier... 

On warming above -30 C the mixture clears and a Pummerer rearrangement occurs to form (methyl-thio)methyl trifluoracetate (13). However the extent of this by-product formation is minimized at Ae lower temperature, and the reaction with alcohols gives high yields of carbonyl products over short reaction times. This makes trifluoroacetic anhydride one of the better activators for dimethyl sulfoxide oxidations. 

Very few reports of competitive reactions of alcohols have appeared in activated dimethyl sulfoxide oxidations, but the results obtained from these limited studies are interesting. It is known that dimethyl sulfoxide-trifluoroacetic anhydride oxidation is selective for primary or secondary alcohols in the presence of benzylic or allylic alcohols, due to the latter alcohols being preferentially converted to trifiu-oroacetates. Additionally, secondary alcohols are known to be more reactive than primary alcohols in these oxidations, although the measured rate differences are not very high and selectivity cannot be guaranteed. 

Acetone, cyclohexanone, benzophenone, cinnamaldehyde, and other carbonyl compounds are hydrogen acceptors in the Oppenauer oxidation of alcohols to carbonyl compounds. The reaction is catalyzed by Raney nickel [961], aluminum alkoxides [962], tris(isopropoxide), or tris(tert-bu-toxide) as bases soluble in organic solvents [963, 964]. These dehydrogenations of alcohols to aldehydes and ketones require refluxing or distillations and have given way to dimethyl sulfoxide oxidations, which take place at room temperature. 

Dimethyl sulfoxide oxidizes primary allylic alcohols in preference to cyclic secondary alcohols [1018] and is suitable for oxidations of sterically hindered alcohols in high yields [1009, 1139] (equation 263). 

Before the discovery of the applications of selenium dioxide and dimethyl sulfoxide, oxidations of methylene groups in 3-diketones or p-keto esters were achieved with nitroso compounds. Thus acetylacetone boiled with p-nitrosodimethylaniline in alcoholic sodium hydroxide gives trike-topentane in 55% yield [986],... 

Epstein, W. W., Ollinger, J. Silver ion assisted dimethyl sulfoxide oxidations of organic halides. J. Chem. Soc., Chem. Common. 1970, 1338-1339. 

Ganem, B., Boeckman, R. K., Jr. Silver-assisted dimethyl sulfoxide oxidations. Improved synthesis of aldehydes and ketones. Tetrahedron Lett. 1974, 917-920. 

Dimethyl sulfoxide oxidizes certain thlo ethers to the sulfoxides in reasonable yield. The ether is heated with a 50% molar excess of DMSO at 160-175° for several hours and the dimethyl sulfide is removed by distillation as formed. The suifoxides were isolated in high purity by distillation and there was no evidence of sulfone formation. Di-n-butyl sulfoxide and tetraethylene sulfoxide were obtained in similar yield, but several sulfides did not react to an appreciable extent. DMSO is a superior reagent for the oxidation of thiols to disulfides. A solution of the thiol in NHj MHj... 

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