Oxidations Moffatt

With DMSO Based Reagents. An alcohol is treated with DMSO, DCC, anhydrous phosphoric acid in what is called Moffatt oxidation. In this way, a primary alcohol can be converted to the aldehyde with no carboxylic acid being produced. 

Direct hydrogenation of key intermediate 248 over the Adams catalyst and subsequent lithium aluminum hydride reduction yielded the two stereoisomeric alcohols 256 and 257, which were separately transformed to ( )-corynantheal (258) and ( )-3-epicorynantheal (259), respectively, by Moffatt oxidation, followed by Wittig reaction with methyltriphenylphosphonium bromide and, finally, by demasking the aldehyde function (151, 152). 

Oxidation of alcohols using DCC and DMSO, also known as Pfitzner-Moffatt oxidation . 

All of the usual chromium-based oxidation reagents that have been used for the oxidation of cyclobutanols to cyclobutanones, for example, chromium(VI) oxide (Jones reagent),302 pyri-dinium chlorochromate,304 pyridinium dichromate,307 and chromium(YI) oxide/pyridine (Collins),303 are reported to do so without any serious problems. Alternatively, tetrapropylam-monium perruthenate in the presence of A-methylmorpholine A -oxide. oxalyl chloride in the presence of triethylamine in dimethyl sulfoxide (Swern),158,309,310 or phenyl dichlorophos-phate in the presence of triethylamine and dimethyl sulfoxide in dichloromethane (Pfitzner-Moffatt),308 can be used. The Pfitzner-Moffatt oxidation procedure is found to be more convenient than the Swern oxidation procedure, especially with respect to the strict temperature control that is necessary to achieve good yields in the latter, e.g. oxidation of 1 to give 2.308... 

With DMSO. provides a mild oxidizing agent (Pfitzner-Moffatt Oxidation). The reagent has been useful in forming the peptide linkage from amino acids. 

Pfitzner-Moffatt oxidation or Dess-Martin periodinane 70-72%... 

Pfitzner-Moffatt Oxidation (Carbodiimide-Mediated Moffatt Oxidation)... 

In variance with other oxidants, such as the chromium-based ones, no carbon-carbon bond breakage is observed in the Pfitzner-Moffatt oxidation of this 1,2-diol. 

The Pfitzner Moffatt oxidation is performed in the presence of a carbo-diimide that is transformed into a form of activated DMSO . As both the carbodiimide and the activated DMSO are strong electrophiles, it would seem reasonable to expect that nucleophilic sites in a molecule would interfere with the oxidation. Nevertheless, Pfitzner-Moffatt oxidations very often can be carried out in the presence of thiols,14b amines40 and amides.23c,d... 

Carboxylic acids react under Pfitzner-Moffatt conditions, resulting in the formation of methylthiomethyl esters and /V-acylureas.41 Nevertheless, although the authors are not aware of any report involving the selective oxidation of alcohols in the presence of a carboxylic acid, such outcome would be likely with carboxylic acids with little nucleophilicity, as standard Pfitzner-Moffatt oxidations are performed in the presence of trifluoroacetate that is known for not to interfere. 

Quite puzzingly, thiols are reported14b to be unreactive under Pfitzner-Moffatt conditions, while this being one of the few oxidation methods for alcohols compatible with this functionality. Sulfides also resist the action of Pfitzner-Moffatt oxidations.42,43... 

In fact, the interference of amines in Pfitzner-Moffatt oxidations very often results from the trivial fact that basic sites in a molecule can quench the acidic catalyst. In such cases, the oxidations must be carried out by adding an excess of one equivalent of acidic catalyst. 

Oxidation-sensitive functionalities other than alcohols are remarkably resistant to the action of the TFAA-mediated Moffatt oxidation. Functional groups resistant to this oxidation include p-methoxybenzyl ethers133 and esters,143 sulfides,143a 144 thioacetals,145 nitrogen heterocycles146 and most peculiarly even selenides,147 and p-hydroquinones.148... 

It is interesting to note that stabilized phosphoranes143a,b and phos-phonate155 anions can resist TFAA-mediated Moffatt oxidations. 

In an enantioselective synthesis of a key intermediate for the preparation of poisons from the skin of tropical frogs, a key oxidation was performed under Swern conditions with 77% yield, while PCC provided a 28% yield and Pfitzner-Moffatt oxidation 73% yield. 

In most Moffatt oxidations, activated DMSO is prepared by the activation of DMSO in a reaction with an electrophile. On the other hand, in a Corey-Kim oxidation, no DMSO is used in the preparation of activated DMSO , which is obtained by oxidation of dimethyl sulfide. 

As in other Moffatt oxidations, a Corey-Kim oxidation may produce minor amounts of methylthiomethyl ethers. These can be minimized by using a solvent of low polarity, like toluene.248a Nonetheless, very often dichloromethane is used, because of its better solubilizing power. Almost always triethylamine is used as base. 

Similar to other Moffatt oxidations, the Corey-Kim method results sometimes in the generation of methylthiomethyl ethers by reaction of alcohols with H2C=S(+)-Me, resulting from decomposition of activated DMSO.259... 

Almost any electrophile, able to react with DMSO, can generate an active DMSO species that can be used for the oxidation of alcohols. Dozens of such activators have been described in the literature as shown in Table 2.2. Many of these activators have been the subject of very superficial analyses and, therefore, their potential for Moffatt oxidation of alcohols is not known in detail. Some of these activators particularly... 

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