The Parikh-Doering oxidation is an oxidation reaction that transforms primary and secondary alcohols into aldehydes and ketones, respectively.[1] The procedure uses DMSO as the oxidant, activated by sulfur trioxide-pyridine complex in the presence of triethylamine base:
The procedure can be run at temperatures close to ambient (usually 0°C) without formation of significant amounts of methylthiomethyl ether side product.[2]
The following example from the total synthesis of (–)-kumausallene by P.A. Evans and coworkers illustrates typical reaction conditions: [3]
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The first step of the Parikh-Doering oxidation is the reaction of dimethyl sulfoxide (DMSO), 1a & 1b, with sulfur trioxide, 2 at 0 oC or room temperature. Then, the intermediate 3 receives a nucleophilic addition from the alcohol to give the key alkoxysulfonium ion intermediate, 6, where the counterweight of positive charge is sulfate coordinated by pyridine.
After that, the addition of at least 2 equivalents of base — typically triethylamine — will deprotonate the alkoxysulfonium ion to give the sulfur ylide 7. The base also helps the charge counterweight to leave. In the last step, through a five-membered ring transition state, the sulfur ylide 7 decomposes to give the desired ketone or aldehyde 8.
Parikh-Doering oxidation is widely applied in organic synthesis. Here is an example of Parikh-Doering oxidation's application in Nicolaou cortistatin total synthesis[4] where the reaction transforms the hydroxyl function group into a aldehyde group. This process leads to Ohira-Bestmann homologation which is critical in following 1,4 addition/aldol condensation/dehydration cascade constructing the cortistatins' seven-membered ring. The synthetic route is shown as below: