Swem reagent

Formation of the dimethylchlorosulfonium species 8 and its reaction with alcohols and also the conversion of the ylide 10 to the product are both rapid at -78 °C. Additionally, formation of (methylthio)methyl ethers, a common side reaction in these procedures, is minimised. The reactive reagent 8 can also be formed directly by the reaction of dimethyl sulfide with chlorine9 " 1 however, the high yields and convenient procedure using the Swem reagents makes it particularly advantageous. 

Many examples exist wherein a silyl enol ether is deprotected and oxidised in a one-pot procedure using Swem conditions. Godfroid and co-workers report the selective oxidation of primary TMS or TES protected 1,2-diols, 1,3-triols, and polyhydroxy compounds to the corresponding silyloxy aldehydes even when using excess Swem reagents.36... 

The versatility and efficiency of the Swem conditions means that they can also be applied to various functional groups to effect different transformations other than just oxidations of alcohols. For example, primary amides have been converted to nitriles using the Swem reagents as dehydrating agents.42 Although different activators of DMSO were tested, for example, the S03-pyridine complex and TFAA, oxalyl chloride was found to be the best based on the yield of the final product. 

The present section reviews the recent apphcations in the activation of dimethyl sulfoxide, with the aim of identifying alternative milder and more practical methods for the oxidation of hydroxylic compounds. Thereafter, we focus on oxalyl dichloride, the classical Swem reagent, on diphosgene and triphosgene, as well as on alternative non-chlorine activation methods. 

Chlorodimethylsulfonium chloride (Swem reagent) represents another metal-free alternative for hydrazone oxidation [54]. The strategy was discovered by chance during research on a new conversion of free hydrazones to alkyl chlorides [159]. When benzophenone hydrazone was exposed to Swern reagent in the absence of an amine base, Brewer and laved observed localized yet transient red coloration of the reaction mixture. Diligent experimentation then led to the... 

The widely used Moifatt-Pfltzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g. DCC, AcjO, SO], P4O10, CCXTl] (K.E, Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffatt, 1971 D. Martin, 1971) or oxalyl dichloride (Swem oxidation M. Nakatsuka, 1990). A classical procedure is the Oppenauer oxidation with ketones and aluminum alkoxide catalysts (C. Djerassi, 1951 H. Lehmann, 1975). All of these reagents also oxidize secondary alcohols to ketones but do not attack C = C double bonds or activated C —H bonds. 

For a review of activated Me2SO reagents and their use in this reaction, see Mancuso, A.J. Swem, D. Synthesis, 1981, 165. 

Stilbenes, photocyclization of, 30, 1 StiUe reaction, 50, 1 Stobbe condensation, 6, 1 Substitution reactions using organocopper reagents, 22, 2 41, 2 Sugars, synthesis by glycosylation with sulfoxides and sulfinates, 64, 2 Sulfide reduction of nitroarenes, 20, 4 Sulfonation of aromatic hydrocarbons and aryl halides, 3, 4 Swem oxidation, 39, 3 53, 1... 

Oxalyl chloride (98%) was purchased from Aldrich Chemical Company, Inc., and used without further purification. Amounts of reagents for the Swem oxidation have been optimized as reported. Alternative amounts reduce both yield and % ee. 

Sulfur trioxide is one of many reagents [e.g.. DCC Ac20, (COC1) TPAA with which DMSO can be activated as an oxidizing reagent lor alcohols. Oxalyl chloride has found the widest application in the reaction named after Swem.Xi Structure 43 represents the activated species in the above oxidation. 

The oxidation of this alcohol can be carried out employing Fetizon s reagent under simple experimental conditions with quantitative yield. Alternatively, a Swem oxidation can be used resulting in 92% yield. 

Oxidation of 1,4-diols. The 1,4-diol 1 is transformed directly into the 1,4-dialdehyde polygodial (2) by oxidation with Swem s reagent.2... 

In the second step the alcohol is transformed to an aldehyde by means of the Swem oxidation. Other reagents to oxidize alcohols to aldehydes are e. g. Dess-Martin-periodinane and chromium reagents like PCC or PDC. 

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

Reduction of the olefinic bond in 12 and Swem oxidation of the free carbinol function provided ketone 53, onto which installation of the methyl group was performed by reaction with methylmagnesium chloride in THF. After protection of the resulting tertiary alcohol as a TBS-ether, fully protected triol 54 was obtained with a useful 80% diastereomeric excess. Acetonide deblocking and oxidative fission of the diol formed led to aldehyde 55, ready for the planned cyclization step. Exposure of aldehyde 55 to TBSOTTDIPEA reagent system smoothly resulted in formation of the desired bicyclic adducts 56 and 57 which were isolated in a 82% combined yield (60 40 ratio). 

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