Parikh- Doering oxidation

The mechanism of the Parikh-Doering oxidation involves formation of O-di-methylsulfoxonium sulfate from the reaction of DMSO with S03. Displacement on the sulfur by the alcohol gives the alkoxysulfonium salt intermediate, which undergoes base-catalyzed elimination to afford the dimethyl sulfide and the aldehyde. This reaction must be carried out so the hydrogen sulfate of the alcohol is not formed first, otherwise no oxidation would occur. 1143 44 ... 

Parikh-Doering Oxidation (Sulfur Trioxide-Mediated Moffatt Oxidation)... 

These results suggest that the Parikh-Doering oxidation should be routinely tried at 0-10°C, rather than at room temperature, as described in the original paper. 

The Parikh-Doering oxidation is conveniently carried out at room temperature or moderately cool temperature. The activator—SO3 Py— generates side compounds that are very easily removed during the workup. In variance with other oxidations involving activating DMSO, the Parikh-Doering oxidation rarely delivers substantial amounts of methylthiomethyl ether side compounds.93 Unlike the Swern oxidation, no chlorinated side compounds are possible. 

After considerable experimentation, it was found that the Parikh-Doering oxidation provides a good and reproducible yield. Under Swern conditions, yields are erratic with substantial quantities of a product, arising from opening of the epoxide by attack of a chloride ion being formed. PCC did not afford a good yield of alcohol. 

While the Parikh-Doering oxidation succeeds, a Swern oxidation produces chlorination at the activated 3-position of the indole. ... 

During the oxidation, an acid-catalyzed cyclization of the product by attack of the nitrogen atoms on the ketone, leading to three different aminals, must be avoided. A Parikh-Doering oxidation gives a good yield of the desired ketone, while PCC, Dess-Martin reagent and Jones oxidation deliver diverse amounts of aminals. 

Functional Group and Protecting Group Sensitivity to Parikh-Doering Oxidation... 

There is a published instance, in which the Parikh-Doering oxidation is made with no interference from a secondary amine.100... 

The Parikh-Doering oxidation provides a very high regioselectivity for the oxidation of alcohols. Oxidation-sensitive functionalities, like indoles,99a,c sulfides,109 and selenides 110 as well as oxidation-sensitive protecting groups, like dithioacetals,111 PMB104 and dimethoxybenzyl ethers109b, do not react. 

It must be mentioned that sensitive compounds, like alkyl silanes,112 alkyl stannanes113 and vinyl stannanes,114 are not affected under the conditions of the Parikh-Doering oxidation. 

In a properly performed Parikh-Doering oxidation, the complex SO3 Py must not interfere, because it must be completely consumed by reaction with DMSO before the substrate is added. In practice, it can be difficult to avoid the presence of minor amounts of S03 Py, that can react with nucleophilic sites in the molecule, including alcohols. 

For an example of isolation of a methylthiomethyl ether in a Parikh-Doering oxidation see Takano, S. Sato, N. Akiyama, M. Ogasawaia, K. Heterocycles 1985,23, 2859. 

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