Baeyer–Villiger oxidation
Baeyer-Villiger oxidation | |||||||||
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Named after | Adolf von Baeyer Victor Villiger | ||||||||
Reaction type | Organic redox reaction | ||||||||
Reaction | |||||||||
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Identifiers | |||||||||
Organic Chemistry Portal | baeyer-villiger-oxidation | ||||||||
RSC ontology ID | RXNO:0000031 | ||||||||
The Baeyer–Villiger oxidation is an
![Baeyer-Villiger oxidation](http://upload.wikimedia.org/wikipedia/commons/thumb/b/b3/Baeyer-Villiger_oxidation.svg/450px-Baeyer-Villiger_oxidation.svg.png)
Reaction mechanism
In the first step of the
![Reaction mechanism of the Baeyer-Villiger oxidation.](http://upload.wikimedia.org/wikipedia/commons/thumb/7/7e/Baeyer-Villiger_oxidation_reaction_mechanism.svg/600px-Baeyer-Villiger_oxidation_reaction_mechanism.svg.png)
The products of the Baeyer–Villiger oxidation are believed to be controlled through both primary and secondary
![Stereoelectronic effects](http://upload.wikimedia.org/wikipedia/commons/thumb/0/08/Baeyer-Villiger_oxidation_stereoelectronic_effects.svg/400px-Baeyer-Villiger_oxidation_stereoelectronic_effects.svg.png)
The migratory ability is ranked tertiary > secondary > aryl > primary.
![Resonance structures of the Criegee intermediate](http://upload.wikimedia.org/wikipedia/commons/thumb/f/fa/Criegee_intermediate_resonance_structures.svg/350px-Criegee_intermediate_resonance_structures.svg.png)
Another explanation uses stereoelectronic effects and steric arguments.
![Steric bulk influencing migration](http://upload.wikimedia.org/wikipedia/commons/thumb/0/06/Criegee_intermediate_stereoelectronics.svg/400px-Criegee_intermediate_stereoelectronics.svg.png)
The migrating group in acyclic ketones, usually, is not 1° alkyl group. However, they may be persuaded to migrate in preference to the 2° or 3° groups by using CF3CO3H or BF3 + H2O2 as reagents.[12]
Historical background
In 1899, Adolf Baeyer and Victor Villiger first published a demonstration of the reaction that we now know as the Baeyer–Villiger oxidation.[13][14] They used peroxymonosulfuric acid to make the corresponding lactones from camphor, menthone, and tetrahydrocarvone.[14][15]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/1/1b/Original_Baeyer-Villiger_oxidation_reactions.png/400px-Original_Baeyer-Villiger_oxidation_reactions.png)
There were three suggested
![](http://upload.wikimedia.org/wikipedia/commons/thumb/c/cb/Proposed_Baeyer_Villiger_Intermediates.png/600px-Proposed_Baeyer_Villiger_Intermediates.png)
In 1953, William von Eggers Doering and Edwin Dorfman elucidated the correct pathway for the reaction mechanism of the Baeyer–Villiger oxidation by using oxygen-18-labelling of benzophenone.[16] The three different mechanisms would each lead to a different distribution of labelled products. The Criegee intermediate would lead to a product only labelled on the carbonyl oxygen.[16] The product of the Wittig and Pieper intermediate is only labeled on the alkoxy group of the ester.[16] The Baeyer and Villiger intermediate leads to a 1:1 distribution of both of the above products.[16] The outcome of the labelling experiment supported the Criegee intermediate,[16] which is now the generally accepted pathway.[1]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/d/d3/Dorfman_and_Doering%27s_Labelling_Experiment.png/600px-Dorfman_and_Doering%27s_Labelling_Experiment.png)
Stereochemistry
The migration does not change the stereochemistry of the group that transfers, i.e.: it is stereoretentive.[18][19]
Reagents
Although many different peroxyacids are used for the Baeyer–Villiger oxidation, some of the more common
Limitations
The use of
![](http://upload.wikimedia.org/wikipedia/commons/thumb/0/09/Reagent_Dependent_Oxidation.png/400px-Reagent_Dependent_Oxidation.png)
Modifications
Catalytic Baeyer-Villiger oxidation
The use of hydrogen peroxide as an
Asymmetric Baeyer-Villiger oxidation
There have been attempts to use
Baeyer-Villiger monooxygenases
![](http://upload.wikimedia.org/wikipedia/commons/thumb/3/36/BVMO_reaction_mechanism.png/490px-BVMO_reaction_mechanism.png)
In nature,
BVMOs are closely related to the flavin-containing monooxygenases (FMOs),[32] enzymes that also occur in the human body, functioning within the frontline metabolic detoxification system of the liver along the cytochrome P450 monooxygenases.[33] Human FMO5 was in fact shown to be able to catalyse Baeyer-Villiger reactions, indicating that the reaction may occur in the human body as well.[34]
BVMOs have been widely studied due to their potential as biocatalysts, that is, for an application in organic synthesis.[35] Considering the environmental concerns for most of the chemical catalysts, the use of enzymes is considered a greener alternative.[29] BVMOs in particular are interesting for application because they fulfil a range of criteria typically sought for in biocatalysis: besides their ability to catalyse a synthetically useful reaction, some natural homologs were found to have a very large substrate scope (i.e. their reactivity was not restricted to a single compound, as often assumed in enzyme catalysis),[36] they can be easily produced on a large scale, and because the three-dimensional structure of many BVMOs has been determined, enzyme engineering could be applied to produce variants with improved thermostability and/or reactivity.[37][38] Another advantage of using enzymes for the reaction is their frequently observed regio- and enantioselectivity, owed to the steric control of substrate orientation during catalysis within the enzyme's active site.[29][35]
Applications
Zoapatanol
Zoapatanol is a biologically active molecule that occurs naturally in the zeopatle plant, which has been used in Mexico to make a tea that can induce menstruation and labor.[39] In 1981, Vinayak Kane and Donald Doyle reported a synthesis of zoapatanol.[40][41] They used the Baeyer–Villiger oxidation to make a lactone that served as a crucial building block that ultimately led to the synthesis of zoapatanol.[40][41]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/6/6d/Synthesis_of_Zoapatanol.png/600px-Synthesis_of_Zoapatanol.png)
Steroids
In 2013, Alina Świzdor reported the transformation of the steroid dehydroepiandrosterone to anticancer agent testololactone by use of a Baeyer–Villiger oxidation induced by fungus that produces Baeyer-Villiger monooxygenases.[42]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/b/b4/Dehydroepiandrosterone_to_testololactone.png/700px-Dehydroepiandrosterone_to_testololactone.png)
See also
- Dakin reaction
References
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