DMSO, activated oxidations with

Oxidation. DMSO activated by P205 (1 equiv.) and in combination with triethylamine is useful for oxidation of alcohols to ketones and aldehydes, particularly in cases where the Swern reagent results in chlorinated byproducts. Yields are typically 80-85%. 

Air oxidation of synthetic fully reduced co-conotoxin GVIA (9) (Scheme 4), a 27-residue peptide, 64 generated a main product that possessed the identical biological activities as the natural product whose cystine framework was determined with the synthetic compound. 65 The choice of buffer system and peptide concentration can, however, dramatically affect the folding efficiency when the DMSO-mediated oxidation method was applied. 661... 

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... 

R OTf 35 R Me acts with the Hu nig base to produce an ammonium fluoride salt. Because of poor ion-pair formation by the ethyldiisopropylammo-nium cation, fluoride ions are present in the free state in solution and can thus act as nucleophiles. The final Swem oxidation with TFAA as activating agent for DMSO (see Chapter l) leads to compound 10.13... 

An interesting consequence of the fast formation of the chromic ester is that, sometimes, chromium-based oxidants counter-intuitively are able to oxidize quicker alcohols possessing a greater steric hindrance, as the initially fonned chromic ester releases greater tension on evolving to a carbonyl. Thus, axial alcohols are oxidized quicker than equatorial ones with chromic acid.6 The reverse—a somehow expected behavior—is observed, for example in oxidations with activated DMSO.7... 

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. 

Very rarely, some quantity of methylthiomethyl ether is formed.93 It must be mentioned that the formation of methylthiomethyl ethers in oxidation with activated DMSO can be minimized by the use of low polarity solvents.117... 

Additionally, it must be mentioned that the formation of methylthio-methyl ethers in oxidations with activated DMSO is minimized by the use of solvents of low polarity.123 Hence, the routine use of CH2CI2—which possesses a good balance of solubilizing power versus low polarity—is practiced in Omura-Sharma-Swern and MofTatt oxidations. The formation of side compounds—both trifluoroacetates and methylthiomethyl ethers—is decreased by using more diluted reaction conditions under Procedure C, while concentration has little effect on the yield in oxidations performed under Procedure A.124... 

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. 

This diol possesses a high tendency to suffer a selective oxidation of the secondary alcohol, which can be performed with 84% using DMSO activated with TFAA or with a lower yield with PDC. According to the authors, who intended to make a selective oxidation of the primary alcohol, however, all attempts to selectively oxidize the primary hydroxy function in the presence of the secondary hydroxy group failed. ... 

A variety of methods have been described to solve the task in solution.16 Common oxidative agents for this transformation include various heavy-metal reagents such as chromium-or ruthenium-based oxides, pyri-dine-S03, and dimethylsulfoxide (DMSO) in combination with acetic anhydride, carbodiimide, or oxalyl chloride for activation. One of the most prominent methods for the reliable conversion of sensitive compounds is the Dess-Martin reagent or its nonacetylated equivalent, 1-hydroxy-(17/)-benzo-l,2-iodoxol-3-one-l-oxide (2-iodoxybenzoic acid, IBX). 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

Oxidation. DMSO in combination with catalytic amounts of iodine and a strong acid oxidizes methylene groups activated by an adjacent benzoyl group in good yield. The method is only suitable for preparation of diaryl di- and triketones. Examples ... 

Protection of aldoses at the non-anomeric positions makes it possible to use many of the common procedures in organic chemistry for oxidizing lactols as shown with mannofura-nose 1 and glucopyranose 3 (O Table 1). The reactions can be divided into three main categories oxidations mediated by activated dimethyl sulfoxide (DMSO), oxidations with chromi-um(VI) oxides, and oxidations catalyzed by ruthenium oxides. The DMSO-mediated oxidations of alcohols can be promoted by several activators [27]. With the partially protected aldoses the activation has mainly been achieved with acetic anhydride and oxalyl chloride. Competing /3-elimination does usually not occur unless the eliminating group is an ester, e. g., an acetate or a benzoate [27]. 

A commonly used, protected carbohydrate containing a secondary hydroxy group is diiso-propylideneglucofuranose 23. Oxidation to the corresponding ketone 24 illustrates some of the most widely applied methods for oxidation of secondary alcohols (O Table 4). Again, the reactions can be divided into three main categories oxidations mediated by activated DMSO, oxidations with chromium(VI) oxides, and oxidations catalyzed by mthenium oxides. For oxidations with activated DMSO the Swern procedure is the most widely used [27]. 

A quite similar method is employed in the one-carbon chain extension of a 5 -phosphonate isostere of pyridoxal 5 -phosphate (Scheme 5.50) The a , 3-O-isopropylideneisopyridoxal is converted into an oc,P-unsaturated phosphonate in yields up to 65% by condensation with sodium tetraethyl methylenediphosphonate. Selective hydrolysis with 10% HCOjH at reflux gives the key diethyl 2-(3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridyl)vinylphosphonate intermediate in 98% yield. After catalytic hydrogenation of the double bond using 5% Pd/C in EtOH, a comparison of methods for the oxidation of the alcohol has been made, including use of MnOi in water, CrO, Py, and DMSO-DCC. Finally, oxidation with activated MnO2 in CHCl, was found to proceed smoothly to give the diethyl 2-(4-formyl-3-hydroxy-2-methyl-5-pyridyl)cthylphosphonate. ... 

Oxidation of alcohols to aldehydes or ketone by DMSO activated with DCC (Pfitzner-Moffat), Ac2Q, (COCI)2, TFA, (Swem), P205l or pyridine-S03 (see 1sted). 

C.iii. Other DMSO Oxidations. Albright and Goldman developed a reagent using DMSO and acetic anhydride that formed an active sulfoxonium complex. 12 jj (jje initial work, yohimbine was oxidized to the ketone (yohimbinone) in 85% yield, at ambient temperatures in 24 h. 2 As with DCC, DMSO initially reacts with acetic anhydride to form sulfoxonium salt 66, which then reacts with the alcohol. Acetate is the leaving... 

TBS-protected lactaldehyde 689 is readily prepared with high enantiomeric purity by a mild oxidation of the propanol 688 under Swem-type conditions using bis(trichloromethyl)car-bonate (triphosgene)-DMSO [203]. Triphosgene is a white crystalline solid that is easily handled, and it is a safe alternative for such other DMSO activators as phosgene or diphosgene dimer. 

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