The Parikh–
Doering 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 grou ...
s and
ketones, respectively. The procedure uses
dimethyl sulfoxide (DMSO) as the oxidant and the solvent, activated by the
sulfur trioxide pyridine complex (SO
3•C
5H
5N) 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 ...
or
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, SO
3•C
5H
5N 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
dimethyl sulfoxide (DMSO), which exists as a hybrid of the
resonance structures
In chemistry, resonance, also called mesomerism, is a way of describing bonding in certain molecules or polyatomic ions by the combination of several contributing structures (or ''forms'', also variously known as ''resonance structures'' or '' ...
1a and 1b, with
sulfur trioxide (2), giving intermediate 3. Nucleophilic attack by alcohol 4 and deprotonation by
pyridine
Pyridine is a basic 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, weakly alkaline, water-miscible liquid with a ...
(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 ...
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 atoms ...
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.
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
{{reflist
See also
*
Swern oxidation
The Swern oxidation, named after Daniel Swern, is a chemical reaction whereby a primary or secondary alcohol is oxidized to an aldehyde or ketone using oxalyl chloride, dimethyl sulfoxide (DMSO) and an organic base, such as triethylamine. It is one ...
*
Pfitzner–Moffatt oxidation
*
Corey–Kim oxidation
Organic oxidation reactions
Name reactions