The Parikh–

Doering Doering is a surname. Notable people with the surname include: *Aaron Doering (born 1971), American professor *Bernd von Doering (1903–1944), German general *Charles R. Doering (born 1956), American professor *Chris Doering (born 1973), American ...

oxidation is an

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

reaction that transforms primary and secondary alcohols into

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl group ...

s and

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...

s, respectively. The procedure uses

dimethyl sulfoxide Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds ...

(DMSO) as the oxidant and the solvent, activated by the sulfur trioxide pyridine complex (SO₃•C₅H₅N) in the presence of

triethylamine Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine or tetraethylammonium, for which TEA ...

diisopropylethylamine ''N'',''N''-Diisopropylethylamine, or Hünig's base, is an organic compound and an amine. It is named after the German chemist Siegfried Hünig. It is used in organic chemistry as a base. It is commonly abbreviated as DIPEA, DIEA, or ''i''-Pr2N ...

as base. Dichloromethane is frequently used as a cosolvent for the reaction. Compared to other activated DMSO oxidations, the Parikh–Doering oxidation is operationally simple: the reaction can be run at non-cryogenic temperatures, often between 0 °C and room temperature, without formation of significant amounts of methyl thiomethylether side products. However, the Parikh–Doering oxidation sometimes requires a large excess of DMSO, SO₃•C₅H₅N and/or base as well as prolonged reaction times for high conversions and yields to be obtained. The following example from the total synthesis of (–)-kumausallene by P.A. Evans and coworkers illustrates typical reaction conditions:

Mechanism

The first step of the Parikh–Doering oxidation is the reaction of

(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 Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakl ...

(5) gives intermediate 6, an alkoxysulfonium ion associated with the anionic

pyridinium Pyridinium refers to the cation . It is the conjugate acid of pyridine. Many related cations are known involving substituted pyridines, e.g. picolines, lutidines, collidines. They are prepared by treating pyridine with acids. As pyridine is oft ...

sulfate complex. The addition of at least two equivalents of base deprotonates the alkoxysulfonium ion to give sulfur

ylide An ylide or ylid () is a neutral dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), and in which both ato ...

7 and removes the pyridinium sulfate counterion. In the last step, the ylide goes through a five-membered ring

transition state In chemistry, the transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked ...

to give the desired ketone or aldehyde 8, as well as an equivalent of

dimethyl sulfide Dimethyl sulfide (DMS) or methylthiomethane is an organosulfur compound with the formula (CH3)2S. Dimethyl sulfide is a flammable liquid that boils at and has a characteristic disagreeable odor. It is a component of the smell produced from co ...

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, 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:

References

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Mechanism

Application

References

See also