Swern method

General Procedure (Procedure A) for Oxidation of Alcohols with Omura-Sharma-Swern Method... 

Functional Group Compatibility. The neutral conditions of these oxidations have been utilized to provide improved yields with acid sensitive substrates compared to the well established Swern method (eqs 9-10). ... 

The challenge of constructing the three chiral centres at the left-hand end of the molecule can be solved by taking just one of them from a natural source—in this case the amino acid L-serine. The amino group of serine was protected as the Boc derivative, and the hydroxyl and amino groups condensed with the dimethoxyacetal of acetone to form a five-membered ring. Now the free ester could be reduced with LiBH4 and oxidized to the aldehyde by the Swern method (Chapter 27). 

Table 4.52 compares the results obtained for the oxidation of alcohols with the triphosgene/DMSO reagent with those obtained using the traditional Swern method (oxalyl chloride/DMSO) [1363]. 

Precursors of imidazoquinoxalines-compounds 109a, b and 112-have been synthesized from chloroquinoxalines 128 and corresponding amines in the presence of EtsN. To oxidize aminoalcohols 112 to ketones 114, different oxidative systems have been used a complex of trimethylamine and sulfuric anhydride in DMSO, chromium(VI) oxide in pyridine (Sarett method) (Luzzio 1998 Caamano et al. 2000), and dichloroxalate in DMSO (Swern method) (Scheme 4.58) (Ohmori et al. 1997 Parra et al. 2001 Deleuze-Masqudfa et al. 2004). 

N-Methyllauramide, N-methyhnyristamide, and N-methyl-pelargonamide can be prepared in 95-98% yield by adaptation of the method used by Roe, Scanlan, and Swern for the preparation of amides of oleic and 9,10-dihydroxystearic acids. 

Epoxidation of olefins with meta-chloroperbenzoic acid, (MCPBA) remains to this day among the most widely used methods for research-scale applications [16], Discovered by Nikolai Prilezahev in 1909 [17], it became popular only decades later, mostly through the works of Daniel Swern in the 1940s [18]. Despite its simplicity, and not unlike most epoxidation methods in use today, it suffers from undesired epoxide opening caused by the slight acidity of the reaction milieu. Although acid-catalyzed side reactions can sometimes be minimized by use of buffered systems... 

Preparatively useful procedures based on acetic anhydride,25 trifluoroacetic anhydride,26 and oxalyl chloride27 have been developed. The last method, known as the Swern oxidation, is currently the most popular. 

Acyl nitroso compounds (3, Scheme 7.2) contain a nitroso group (-N=0) directly attached to a carbonyl carbon. Oxidation of an N-acyl hydroxylamine derivative provides the most direct method for the preparation of acyl C-nitroso compounds [10]. Treatment of hydroxamic acids, N-hydroxy carbamates or N-hydroxyureas with sodium periodate or tetra-alkyl ammonium periodate salts results in the formation of the corresponding acyl nitroso species (Scheme 7.2) [11-14]. Other oxidants including the Dess-Martin periodinane and both ruthenium (II) and iridium (I) based species efficiently convert N-acyl hydroxylamines to the corresponding acyl nitroso compounds [15-18]. The Swern oxidation also provides a useful alternative procedure for the oxidative preparation of acyl nitroso species [19]. Horseradish peroxidase (HRP) catalyzed oxidation of N-hydroxyurea with hydrogen peroxide forms an acyl nitroso species, which can be trapped with 1, 3-cyclohexanone, giving evidence of the formation of these species with enzymatic oxidants [20]. 

X = CH(OH)R] to butadienals [166-168] and allenyl ketones [137, 169-171], respectively. Using particularly the Swern or Dess-Martin oxidation methods, very high yields can be achieved [166, 172,173],... 

Oxidation of the quinine C-9 hydroxy substituent to the ketone is best accomplished using the Woodward3 benzophenone/potassium t-butoxide method, now using toluene. The other oxidation methods investigated (Swern, Jones, ROCI variations) were less effective or limited because of the poor solubility of the substrate. Thermodynamic equilibration of these ketones has also been reported.3... 

A fluorous analogue of DMSO has been used to perform Swern reactions [24], This widely used method of oxidizing an alcohol to an aldehyde falls down seriously from the environmental point of view due to its production of a stoichiometric amount of dimethyl sulfide. Here, a fluorous sulfoxide is prepared and used in the oxidation of several alcohols in dichloromethane, as shown in Scheme 9.12. After reaction, the sulfide is extracted into perfluorohexane and the system recycled. Unfortunately, extraction from dichloromethane was found to be difficult, but replacing the dichloromethane with toluene leads to a more efficient recovery. 

Preparatively useful procedures based on acetic anhydride,20 trifluoroacetic anhydride,21 and oxalyl chloride22 have been developed. The latter method, known as Swern oxidation, is currently the most popular and is frequently preferred to Cr(VI) oxidation. Scheme 12.3 gives some representative examples of these methods. Entry 4 is an example of the use of a water-soluble carbodiimide as the activating reagent. The modified carbodiimide facilitates product purification by providing for easy removal of the urea by-product. 

Further oxidation of an aldehyde prodnct to the corresponding carboxylic acid does not take place. Moreover, the Swern oxidation reaction does not reqnire the nse of toxic and pollntant chromium reagents. The activated DMSO species, however, are stable only at low temperatnre, which might in some cases be a drawback of this method. 

The present method offers a more efficient and convenient two-step route to the parent a,B-unsaturated acylsilane derivative. The first step in the procedure involves the conversion of allyl alcohol to allyl trimethylsilyl ether, followed by metalation (in the same flask) with tert-butyllithiura at -75°C. Protonation of the resulting mixture of interconverting lithium derivatives (2 and 3) with aqueous ammonium chloride solution furnishes (1-hydroxy-2-propenyl)trimethylsilane (4), which is smoothly transformed to (1-oxo-2-propenyl)trimethylsilane by Swern oxidation. The acylsilane is obtained in 53-68% overall yield from allyl alcohol in this fashion. 

The dimethyl sulfoxide (Me2SO)-dicyclohexyl carbodiimide (DCC) method described by Pfitzner and Moffatt24 opened a route to keto derivatives of aldopentosylpyrimidines,2,25 as well as to many keto derivatives of hexosyl-purines3,7,26-31 and -pyrimidines.30,32,33 An alternative proposed by Swern and coworkers,34 requiring the presence of oxalyl chloride as an activating agent, has been used to prepare 4-keto-lyxo-hexose C-nucleosides.13... 

Few oxidation methods have enjoyed the almost immediate success of the Swern procedure for the oxidation of alcohols. Since the publication of three foundational papers161 in 1978-79, Swern has become the de facto oxidation method by default whenever activated DMSO is desired. It offers the advantage of quite consistent good yields in many substrates, with an operation performed under very low temperature and mild conditions. Swern s procedure consists of the oxidation of an alcohol using DMSO, activated by reaction with oxalyl chloride. According to Swern, oxalyl chloride is the most effective activator of DMSO examined by his group.162 It must be mentioned that Swern s research team is probably the one that has tried the highest number of DMSO activators for the oxidation of alcohols. 

A very reactive ketone, obtained by Swern oxidation, is condensed in one-pot with MeMgBr. Other oxidation methods lead to the isolation of the ketone hydrate, which fails to react efficiently with Grignard reagents. 

The activation of DMSO by electrophilic reagents such as oxallyl chloride or trifluoroacetic anhydride (TFAA) (among many others) produces an oxidant capable of oxidizing primary alcohols to aldehydes in high yields. This oxidation is called the Swern oxidation and yields the aldehyde (oxidized product) by reductive elimination of dimethylsulfide (reduced product) and proceeds under mild, slightly basic conditions. It is a second widely used and effective oxidative method for the production of aldehydes from primary alcohols. 

NaBH4 provides a method to reduce the ester 54 to alcohol 55. The additive LiCl is used to enhance the reactivity of NaBH4 towards esters.10 Alcohol 55 is then oxidized to aldehyde 11 using Swern conditions with (COCl)2 and DMSO (see Chapter 2). 

Catalytic oxidation of alcohols with molecular oxygen has attracted much attention as an alternative to traditional oxidation methods such as Dess-Martin [195], Jones [196] or Swern [197] oxidations, which require the use of stoichiometric toxic reagents and/or low temperatures. Significant advances have been made in Pd-catalyzed aerobic alcohol oxidations in the last few years [198-200] Sigman and co-workers have shown the broad scope of two IPr-Pd(II) complexes with low catalyst loadings and mild temperatures [201,202]. Some representative examples are summarized in Table 7. 

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