Swem method

A recent paper reports the oxidation of benzylic a-hydroxyphosphonates to aroylphos-phonates in good yields, by refluxing them with 10 equiv. of Mn02 in toluene The same paper reports that other oxidizing agents, including pyridinum chlorochromate and dichlorodicyanobenzoquinone (DDQ),or the Swem method are also applicable for the oxidation of benzylic a-hydroxyphosphonates to benzoylphosphonates. This approach to acylphosphonates was found, however, to be limited to tert-huty esters. ... 

Activated sulfoxides are well-known for use as electrophiles (Swem method). The polymerization of the sulfoxide compound is initiated via the sulfonium cation as an active species by the protonation on the oxygen of the sulfoxide bond. The active species electrophilically substitutes on the benzene ring to eliminate water. 

There are several methods reported in the literature for transforming vicinal diols into ct-diketones while avoiding the risk of C-C bond cleavage.26 Examples include the standard Swem conditions (dimethyl sulfoxide and oxalyl chloride followed by triethylamine), or the use of DMSO activated by acetic anhydride, pyridine-sulfur trioxide complex, or dicyclohexylcarbodiimide (Mq/J-att oxidation). Diones are also obtained by treatment with benzalacetone as a hydride acceptor in the presence of catalytic amounts of tris(triphenylphosphine)ruthenium dichlonde [(PPh RuCFl.27 Recent developments include the use of w-iodoxyben/.oic acid28 or the oxoammonium salt of 4-acctamidoletramethylpipcridine-1-oxyl and y -toluencNulfonic acid.29... 

Finally, chiral 2//-azirine-2-carboxylic esters 128 can be prepared from the corresponding aziridines 127 under mild Swem oxidation conditions. This method, which is effective for both cis and trans substrates, introduces the double bond regioselectively at the "non-conjugated" site [95TL4665]. 

A new synthesis of reserpine (Scheme 19)60 makes use of a very neat synthesis of cw-hydroisoquinoline derivatives, e.g. (Ill), by means of a Diels- Alder /Cope rearrangement sequence. Manipulation of (111) by unexceptional methods then gives (112), which possesses the required stereochemistry in ring E. Oxidative cyclization of (112) affords 3-isoreserpinediol (113) but, unfortunately, some inside isomer, originating from the cyclization of C-2 with C-21, is also obtained. The synthesis also loses some elegance in the multi-stage conversion of 3-isoreserpinediol into 3-isoreserpine (114), since, in the Swem oxidation of the C-16 aldehyde cyanhydrin by means of DMSO with oxalyl chloride as activator, the over-oxidized products (115) and (116) were obtained. However, reduction of (115) gave 3-isoreserpine (114), which has previously been converted into reserpine by four different methods. 

Newer methods of alcohol oxidation (Swem, Dess-Martin) are introduced as environmentally preferable to the older chromium methods, including a description of a general, unifying mechanism of alcohol oxidation to aldehydes and ketones. TEMPO is shown as an oxidation catalyst to enhance hypochlorite oxidation. 

We shall leave detailed discussion of one more method till much later, in Chapter 46, since the mechanism involves some sulfur chemistry you will meet there. But we introduce it here because of its synthetic importance. Known as the Swem oxidation, it uses a sulfoxide [S(IV)1 as the oxidizing agent. The sulfoxide is reduced to a sulfide, while the alcohol is oxidized to an aldehyde. 

Undoubtedly the most popular variation of these oxidations is the use of oxalyl chloride to activate the dimethyl sulfoxide, which is commonly referred to as the Swem oxidation. The advantages of the method are the mild conditions the ease of work-up, due to two of the main by-products being carbon monoxide and carbon dioxide the low yields, if any, of Pummerer rearrangement products and the fact... 

Amongst the more sensitive substrates which can be tolerated during the Swem oxidation is the formation of the aldehyde (24), which noimally undergoes very rapid epimerization in the presence of a trace of acid. Another example which serves to demcmstrate the advantages of the Swem oxidation over other methods is the fonnation of the lactol (25), which is prepared in the presence of a sensitive vinylsilane group"... 

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. 

Swem, D Org React 1953, 7, 378-433, Hamson, I T, Harrison, S. "Compendium of Organic Synthetic Methods , Wiley-Interscience New York, 1971, Vol 1, pp 325-326, Hamson, I T, Harrison, S Compendium of Organic Synthetic Methods , Wiley-Interscience New York, 1974, Vol 2, pp 134-135... 

Aldehydes are one of the most impotent synthons in organic chemistry. Many methods of preparation of formyl carboranes have been discussed previously (E. I. Rosemund method,14 Sonn-Miller reaction,14 reaction of dodecaborane with diacylal of propargyl aldehyde,14 Swem Oxidation15). Since oxazolines are rather good reagents for the preparation of aldehydes and nitriles, we developed a method of preparation of carboranyl oxazolines (Scheme 9). 

Trifluoroacetic anhydride (TFAA) is also a very potent activator for DMSO and concomitant trifluoroacetylation of the starting alcohol is usually not observed [27]. Both the Swem and the TFAA procedure are carried out at low temperature to prevent undesired side reactions, particularly formation of the methylthiomethyl ether. Before these two methods became developed, acetic anhydride was often used for DMSO activation. Flowever, the oxidation under these conditions is slower and the methylthiomethyl ether byproduct is often observed [27]. 

The method described is essentially that of Swem, Billen, Findley, and Scanlan. /mM5-l,2-Cyclohexanediol also has been prepared by hydrolysis of cyclohexene oxide. j-l,2-Cydo-hexanediol has been prepared by the reaction of cyclohexene with hydrogen peroxide in tertiary butyl alcohol with osmium tetroxide as a catalyst. Hydrogenation of catechol over Raney nickel catalyst at 150° gives a mixture (m.p. 73-77°) of cis- and trans-1,2-cyclohexanediols. ... 

Peradds. Swem s group found this acid to be superior to sulfuric acid as the solvent and catalyst for the conversion of carboxylic acids into peroxy acids. It can be used even with some acids containing acid-labile groups. It has good solvent power for carboxylic acids, but the peroxy acid usually precipitates from the medium as it is formed. Peracids are obtained in 75-98% yield from /-butyl-, o- and p-nitro-, and p-cyanobenzoic acid, terephthalic acid, lauric acid, palmitic acid, stearic acid, 12-hydroxystearic acid, and a-bromostearic acid. The method failed with m- and p-methoxybenzoic acid. 

Purification. Brown et aV cite references to four methods of purification of oleic acid. Swern s group describe a procedure involving low-temperature crystallization, distillation, and distillation of the ester. However, in a procedure for the preparation of rhreo-9,10-dihydroxystearic acid by performic acid hydroxylation of oleic acid, Swem et al. state that their method of purifying oleic acid is lengthier and less convenient than purification of the dihydroxy acid. 

Linstead and Whalley showed that urea complexes can be used for effective separation of straight- and branched-chain carboxylic esters. Swem s group used the method to advantage in working up autoxidized methyl oleate for isolation of long-chain hydroperoxides. These peroxides behave like branched-chain compounds because of the bulky peroxide group and remain in solution when nonperoxidic components of the mixture are precipitated as urea complexes. 

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