Sulfoxide, dimethyl activated

Dimethyl sulfide is toxic and possesses a very bad odour. Particularly, in reactions with activated DMSO on a very big scale, it may be advisable to destroy the dimethyl sulfide, generated during the reaction, by purging the reaction mixture with a nitrogen flow, and scrubbing the resulting gaseous mixture with aqueous NaOCl.5 

The activated DMSO 9 can also suffer an elimination, resulting in the highly reactive H2C=S(+)-CH3 species that can react with the alcohol, yielding a methylthiomethyl ether 13 as a side compound. Fortunately, this elimination demands a higher temperature than the normal temperature of oxidation, and a proper control of the temperature minimizes the formation of the methylthiomethyl ether side compound. 

Using solvents of low polarity also minimizes the fonnation of methylthiomethyl ethers.6 That is why, oxidations with activated DMSO are normally carried out in CH2CI2, a solvent of low polarity possessing good solubilizing power. 

The H-NMR spectra of methylthiomethyl ethers (R-OCH2-SCH3) shows the methyl group as a singlet at ca. 2.1-2.3 ppm, and the methylene group as a singlet or as an AB quartet at ca. 4.6-4.8 ppm. 

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The S >ern oxidation is a preparatively important reaction which allows for the oxidation of primary and secondary alcohols 1 to aldehydes and ketones 2, respectively, under mild conditions, using activated dimethyl sulfoxide (DMSO) as the oxidizing agent. 

The ionic species 5, as well as 6, represent the so-called activated dimethyl sulfoxide. Variants using reagents other than oxalyl chloride for the activation of DMSO are known. In the reaction with an alcohol 1, species 5, as well as 6, leads to the formation of a sulfonium salt 7 ... 

Derived reagents. Mancuso and Swern2 have reviewed activated dimethyl sulfoxide reagents (100 references). Activation of DMSO with cither trifhioroacelic anhydride (7, 136) or oxalyl chloride (8, 200) provides the most generally useful... 

Oxidations of Alcohols with Activated Dimethyl Sulfoxide... 

A. J. Mancuso, D. Swem, Activated Dimethyl Sulfoxide Useful Reagents for Synthesis, Synthesis 1981, 165. 

T. T. Tidwell, Oxidation of alcohols by activated dimethyl sulfoxide and related reactions an update, Synthesis 1990, 857-870. 

Alternatively it is possible to oxidize a primary alcohol no further than to give the aldehyde. This is the domain of the Collins reagent, PCC, PDC, or activated dimethyl sulfoxide. The oxidation of primary alcohols with K2Cr207 in aqueous solution to nothing but the aldehyde, (i.e., without further oxidation to the carboxylic acid) is possible only if a volatile aldehyde results and is distilled off as it is formed. This is the only way to prevent the further oxidation of the aldehyde in the (aqueous) reaction mixture. Selective oxidations of primary alcohols to aldehydes with the Jones reagent succeed only for allylic and benzylic alcohols. Otherwise, the Jones reagent directly converts alcohols into carboxylic acids (see above). 

Activation temperatures of about -60 C are typically used to fcxm the activated dimethyl sulfoxide in-temiediate (19), which arises by spontaneous loss of carbon dioxide and carbon monoxide from an initially foimed salt (Scheme 6). 

The unsaturated branched chain sugar (22 equation 11) was successfully converted to an enone under the Swem conditions and the allylic alcohol (23), containing an a,p-unsaturated amide, was smoothly oxidized by this activated dimethyl sulfoxide reaction. ... 

As with trifluoroacetic anhydride, activation of dimethyl sulfoxide with thionyl chloride must be carried out at low temperatures as the reaction is highly exothenmic. Besides the higher yields, a further advantage of thionyl chloride to activate dimethyl sulfoxide over anhydrides is the lack of Pummerer rearrangement products or of esters formed as by-products (as long as Ae reactions are carried out below -60 C). This is amply demonstrated by the oxidation of (-)-bomeol which proceeds in an excellent 99% yield (equation 12). ... 

Attempted use of chlorosuccinimide or A(-bromosucciiiiinide to activate dimethyl sulfoxide is limited, owing to the preferential foimation of methylene acetals in good yields, as illustrated in the preparation of die acetal (28 equation 13). 

A large number of other materials have been used to activate dimethyl sulfoxide for the oxidation of primary and secondary alcohols and new methods are still being introduced. The vast majority of these reactions proceed via an alkoxysulfonium salt and consequently are variants of the original Pfitzner-Moffatt procedure. Very few of tiiese methods have been exhaustively tested and their advantages are often not apparent. 

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... 

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. 

The range of substrates which have been oxidized by activated dimethyl sulfoxide covers a wide range of tolerant functional groups, and there are many reports of how these oxidations proved superior to others that were investigated. 

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... 

The key to successfully using dimethyl sulfoxide as an oxidant for alcohols is to activate the sulfur atom prior to reaction with a nucleophilic alcohol function. This activation involves electrophilic attarlr upon the sulfinyl oxygen by a varied of electrophiles. The initial product formed when an alcohol does attack the activated dimethyl sulfoxide is known to be the sulfonium salt (1 Scheme 1). 

Activated 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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