Oxalyl chloride, DMSO activator

Oxidation of alcohols.1 This phosphate is apparently as efficient as oxalyl chloride for activation of DMSO for oxidation, and the derived reagent is less prone to give chlorine-containing byproducts. The reactions are rapid at 20° or below, and yields are generally 75-95%. 

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). 

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. 

The use of triphosgene as a DM SO activator has several advantages over oxalyl chloride. It is a solid that can be weighed accurately and is less susceptible to hydrolysis. Furthermore, the oxidation of yS-phenylethanols with triphosgene/DMSO gave better yields compared to oxidation with oxalyl chloride/DMSO or TFAA/ DMSO [1363]. 

The ionic species 5, as well as 6, represent the so-called activated dimethyl sulfoxide. Variants using reagents other than oxalyl chloride for the activation of DMSO are known. In the reaction with an alcohol 1, species 5, as well as 6, leads to the formation of a sulfonium salt 7 ... 

Derived reagents. Mancuso and Swern2 have reviewed activated dimethyl sulfoxide reagents (100 references). Activation of DMSO with cither trifhioroacelic anhydride (7, 136) or oxalyl chloride (8, 200) provides the most generally useful... 

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... 

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. 

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. 

The primary product (29) of the reaction of DMSO and oxalyl chloride decomposes very quickly to 30 even at — 140°C.163 However, the activated DMSO molecule 30 remains stable bellow —20°C, but decomposes above this temperature to chloromethyl methyl sulfide (31), via the reactive species H2C=S(+)-Me. 

Interestingly, oxalyl chloride reacts quicker with DMSO than alcohols. Therefore, although not common,164 it is possible to generate an activated alcohol by the addition of oxalyl chloride over a mixture of alcohol and DMSO. 

Protecting groups that are cleaved by an oxidant, like p-methoxyben-zyl201 and dimethoxybenzyl202 ethers or p-methoxybenzylidene203 and dimethoxybenzylidene204 acetals, resist the action of oxalyl chloride-activated DMSO. 

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... 

In a typical example, 10 mmol of an alcohol, 11 mmol of oxalyl chloride, and 24 mmol of DMSO in 40 mL of dichloromethane react at -60 °C. The mixture is then made alkaline with 50 mmol of triethylamine [1023] (equation 262). In other instances, the molar ratios of the alcohol to DMSO and to the activator (benzoic anhydride) were 1 47 and 1 17, respectively with phosphorus pentoxide as the activator, the respective molar ratios were 1 47 and 1 1 [1009], and with pyridine-sulfur trioxide, they were 1 70 and 1 3 [1018]. Dichloromethane and toluene [1012] are the best solvents. 

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]. 

In the widely used Swern oxidation4 of primary and secondary alcohols to carbonyl compounds via alkoxysulfonium ylides, the DMSO is activated by oxalyl chloride (23) (Scheme 14). 

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. 

Swern also found that oxalyl chloride activates DMSO for the oxidation of alcohols. ... 

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