Parikh–Doering oxidation
The Parikh–Doering oxidation is an oxidation reaction that transforms primary and secondary alcohols into aldehydes and ketones, respectively.[1] The procedure uses dimethyl sulfoxide (DMSO) as the oxidant, activated by the sulfur trioxide pyridine complex in the presence of triethylamine base.
![](../I/m/Parikh-doeringscheme.png)
Parikh–Doering oxidation | |
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Named after | Jekishan R. Parikh William von Eggers Doering |
Reaction type | Organic redox reaction |
The reaction can be run at mild temperatures, often between 0 °C and room temperature, without formation of significant amounts of methyl thiomethylether side products.[2] The following example from the total synthesis of (–)-kumausallene by P.A. Evans and coworkers illustrates typical reaction conditions:[3]
![](../I/m/Parikh-doeringexample.png)
Mechanism
The first step of the Parikh–Doering oxidation is the reaction of dimethyl sulfoxide (DMSO), which exists as a hybrid of the resonance structures 1a and 1b, with sulfur trioxide (2), giving intermediate 3. Nucleophilic attack by alcohol 4 and deprotonation by pyridine (5) gives intermediate 6, an alkoxysulfonium ion associated with the anionic pyridinium sulfate complex.
![](../I/m/Mechanism_of_the_Parikh-Doering_Oxidation_-_Part_1.png)
The addition of at least two equivalents of base deprotonates the alkoxysulfonium ion to give sulfur ylide 7 and removes the pyridinium sulfate counterion. In the last step, the ylide goes through a five-membered ring transition state to give the desired ketone or aldehyde 8, as well as an equivalent of dimethyl sulfide.
![](../I/m/Mechanism_of_the_Parikh-Doering_Oxidation_(Part_2).png)
Application
Parikh–Doering oxidation is widely applied in organic synthesis. Here is an example of the Parikh–Doering oxidation's application in the Nicolaou cortistatin total synthesis,[4] where the reaction transforms the hydroxyl functional group into an aldehyde. This process leads to Ohira-Bestmann homologation, which is critical in the following 1,4 addition/aldol condensation/dehydration cascade that forms cortistatins' seven-membered ring. The synthetic route is shown below:
![](../I/m/Parikh-Doering's_strategic_application_on_cortistatin2.png)
References
- Tidwell, Thomas T. (1990). "Oxidation of Alcohols to Carbonyl Compounds via Alkoxysulfonium Ylides: The Moffatt, Swern, and Related Oxidations". Organic Reactions. 39: 297. doi:10.1002/0471264180.or039.03.
- Parikh, J. R.; Doering, W. v. E. (1967). "Sulfur Trioxide in the Oxidation of Alcohols by Dimethyl Sulfoxide". Journal of the American Chemical Society. 89: 5505–5507. doi:10.1021/ja00997a067.
- Evans, P. A.; Murthy, V. S.; Roseman, J. D.; Rheingold, A. L. (1999). "Enantioselective Total Synthesis of the Nonisoprenoid Sesquiterpene (-)-Kumausallene". Angewandte Chemie International Edition. 38: 3175–3177. doi:10.1002/(SICI)1521-3773(19991102)38:21<3175::AID-ANIE3175>3.0.CO;2-M.
- Nicolaou, K. C.; Peng, Xiao-Shui; Sun, Ya-Ping; Polet, Damien; Zou, Bin; Lim, Chek Shik; Chen, David Y.-K. (2009). "Total Synthesis and Biological Evaluation of Cortistatins A and J and Analogues Thereof". Journal of the American Chemical Society. 131 (30): 10587–10597. doi:10.1021/ja902939t. PMID 19722632.