Dimethyl sulfoxide activators

Ube Industries LtdinYamaguchi, Japan, and Kyoto University investigated the Swern oxidation for pharmaceutical intermediates [57,58]. In this reaction, alcohols are oxidized to carbonyl compounds using dimethyl sulfoxide. The reaction variant using dimethyl sulfoxide activated by trifluoroacetic anhydride (shown below) has found industrial application, but is limited to low-temperature operation (—50 °C or below) to avoid decomposition of an intermediate. 

The relatively mild conditions of this dimethyl sulfoxide activation method have been used to good effect to oxidize many sensitive substrates. For instance the alcohol (20 equation 10) was smoothly converted to the aldehyde without any racemization occurring, which can be a problem with other oxidizing systems. Similar advantages were noted in the oxidation of the alcohol (21), thus demonstrating the compatibili of some sensitive protecting groups to the reaction conditions. ... 

The above discussion has concentrated upon the reagents used, but it is equally of value to comment on the substrate, particularly in reactions for which other oxidation methods have been reported to fail. A good example is the oxidation of the iron-carbonyl complex (31) to the ketone (32 equation 14). The use of dimethyl sulfoxide activated with sulfur trioxide-pyridine complex gave a 70% yield of the product, in contrast to the use of the Pfitzner-Moffatt procedure (dimethyl sulfoxide-DCC) or the chromium... 

Despite this, some useful oxidations have been achieved using the method, such as that of yohimbine to yohimbinone in 85% yield, which compares well with that achieved by using dimethyl sulfoxide activated with dicylohexylcarbodiimide. The method has also been successfully applied to the oxidation of carbohydrates, as shown by the formation of (11 equation 6), and aromatic a-diketones can be efficiently prepared using this method by oxidation of the corresponding acyloin products. Unfortunately this methodology cannot be extended to the more useful aliphatic diketones. ... 

An area of recent intense synthetic endeavor has been in the syntiiesis of the avermectins and milbe-mycins, which contain a range of highly reactive functionalities such as the spiroacetal group, double bonds, and epimerizable centers. However, dimethyl sulfoxide activated oxidations, most notably the Swem variation, have teen useful in this area of chemistry. For example, the sensitive spiroacetal (34) gave 92% of the derived aldehyde using dimetiiyl sulfoxide-oxalyl chloride-triethylamine at -SO C (equation 15). ... 

The oxidation of diols having alcoholic groups of the same nature, for example, both alcoholic groups are primary, secondary, allylic, or benzylic, is usually carried out at both groups to yield dialdehydes [832] or diketones [552], Such reactions are achieved by chromium trioxide [582], barium manganate [832], dimethyl sulfoxide activated with acetic anhydride [1013], and others (equations 284 and 285). 

Roa-Gutierrez, F., Liu, H.-J. Use of silyl chlorides as dimethyl sulfoxide activators for the oxidation of alcohols. Bulletin of the Institute of... 

Oxidations using dimethyl sulfoxide activated by various reagents began with discoveries by Komblum and co-workers that primary tosylates and certain a-bromo ketones could be converted into aldehydes and glycoxals, respectively, by treatment with dimethyl sulfoxide as the oxidising agent. This was followed by the discovery several years later by Pfitzner and Moffatt that alcohols could be oxidised to carbonyl compounds with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC) and phosphoric acid at room temperature.2 Eventually the method developed by Swern and co-workers, involving activation of dimethyl sulfoxide with oxalyl chloride, came to be the most synthetically useful and widely applied of these mild oxidation procedures.3-6... 

Mancuso A, Huang SL, Swem D (1987) Oxidation of Long-chain and Related Alcohols to Carbonyls by Dimethyl Sulfoxide "Activated" by Oxalyl Chloride. J Org Chem 43 2480... 

Mancuso, A. J. Swern, D. Activated Dimethyl Sulfoxide Useful Reagents for Synthesis Synthesis 1981,165-185. Mancuso, A. J. Brownfain, D. S. Swern, D. Structure of the Dimethyl Sulfoxide-Oxalyl Chloride Reaction Product. Oxidation of Heteroaromatic and Diverse Alcohols to Carbonyl Compounds /. Org. Chem. 1979, 44, 4148-4150. Mancuso, A. J. Huang, S-L. Swern, E. Oxidation of Long-Chain and Related Alcohols to Carbonyls by Dimethyl Sulfoxide Activated by Oxalyl Chloride J. Org. Chem. 1978, 45, 2480-2482. Omura, K. Swern, D. Oxidation of Alcohols by Activated Dimethyl Sulfoxide. A Preparative Steric and Mechanistic Study Tetrahedron 1978, 54, 1651-1660. 

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