- Baeyer-Villiger oxidation
The Baeyer-Villiger oxidation is an
organic reaction in which aketone is oxidized to anester by treatment withperoxy acid s orhydrogen peroxide .cite journal | authorlink = Adolf von Baeyer | last = Baeyer | first = A. | coauthors = Villiger, V. | title = Einwirkung des Caro'schen Reagens auf Ketone | journal = Ber. | date = 1899 | volume = 32 | issue = 3 | pages = 3625–3633 | doi = 10.1002/cber.189903203151 | url = http://www3.interscience.wiley.com/cgi-bin/abstract/112379267/ABSTRACT | format = abstract ] cite journal | authorlink = Adolf von Baeyer | last = Baeyer | first = A. | coauthors = Villiger, V. | title = Ueber die Einwirkung des Caro'schen Reagens auf Ketone | journal = Ber. | date = 1900 | volume = 33 | issue = 1 | pages = 858–864 | doi = 10.1002/cber.190003301153 | url = http://www3.interscience.wiley.com/cgi-bin/abstract/112334541/ABSTRACT | format = abstract ] Key features of the Baeyer-Villiger oxidation are its stereospecificity and predictableregiochemistry .cite journal | author = Crudden, C. M.; Chen, A. C.; Calhoun, L. A. | title = A Demonstration of the Primary Stereoelectronic Effect in the Baeyer-Villiger Oxidation of α-Fluorocyclohexanones | journal = Angew. Chem. Int. Ed. | date = 2000 | volume = 39 | issue = 16 | pages = 2851–2855 | doi = 10.1002/1521-3773(20000818)39:16<2851::AID-ANIE2851>3.0.CO;2-Y] It is named after the German chemistJohann Friedrich Wilhelm Adolf von Baeyer (1835-1917) and the Swiss chemistVictor Villiger (1868-1934).Reagents typically used to carry out this rearrangement are "meta"-chloroperoxybenzoic acid (mCPBA),
peroxyacetic acid , orperoxytrifluoroacetic acid .cite journal | author = Burton, J.W.; Clark, J.S.; Derrer, S.; Stork, T.C.; Bendall, J.G.; Holmes, A.B. | title = Synthesis of Medium Ring Ethers. 5. The Synthesis of (+)-Laurencin | journal = J. Am. Chem. Soc. | date = 1997 | volume = 119 | issue = 32 | pages = 7483–7498 | doi = 10.1021/ja9709132 | url = http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/1997/119/i32/abs/ja9709132.html | format = Abstract ] Reactive or strained ketones (cyclobutanones, norbornanones) react withhydrogen peroxide orhydroperoxide s to form lactones. The original reagent in the 1899 publication isCaro's acid discovered just a year earlier. [cite journal
author = Michael Renz, Bernard Meunier
title = 100 Years of Baeyer-Villiger Oxidations
journal = European Journal of Organic Chemistry
volume = 1999
issue = 4
pages = 737–750
year = 1999
doi = 10.1002/(SICI)1099-0690(199904)1999:4<737::AID-EJOC737>3.0.CO;2-B]Disodium phosphate orsodium bicarbonate is often added as abuffering agent to preventtransesterification or hydrolysis.Mechanism
The
reaction mechanism of this oxidative cleavage involves first addition of the peroxy acid to the carbonyl forming a tetrahedral intermediate also called theCriegee intermediate for its similarity with rearrangement of that name. The transition state for this step is envisioned as a hydrogen relay involving three peroxy acid molecules with linear O-H-O interactions."The Role of Hydrogen Bonds in Baeyer-Villiger Reactions" Shinichi Yamabe and Shoko YamazakiJ. Org. Chem. ; 2007; 72(8) pp 3031 - 3041; (Article) DOI|10.1021/jo0626562] Next is a concerted migration of one of the adjacent carbons to oxygen with loss of acarboxylic acid . If the migrating carbon is chiral, the stereochemistry is retained.:Migratory aptitude: H > tertiary alkyl > cyclohexyl > secondary alkyl, aryl > primary alkyl > methyl
In the
transition state for this migration step the R-C-O-Odihedral angle should be 180° in order to maximise the interaction between the filled R-Csigma bond and theantibonding O-O sigma bond. This step is also (at leastin silico ) assisted by two or three peroxyacid units enabling the hydroxyl proton to shuttle to its new position.For unsymmetrical ketones, the migrating group is usually the one that can best stabilize positive charge. Thus, cyclic ketones produce
lactone s and aldehydes usually producecarboxylic acid s, althoughformate s can also be formed if the migrating group is tertiary or an electron rich vinyl group or aromatic ring (Dakin reaction ). Sometimes thealcohol is formed when the formate is hydrolytically unstable.Biocatalytic BV oxidation
The Baeyer-Villiger oxidation can also be performed by
biocatalysis with a so-called Baeyer-Villiger monooxygenase or BVMO. Though largely an experimental technique it shows the promise ofenantioselectivity andgreen chemistry for this reaction type. Current stumbling blocks are confinement to water as the reaction medium, substrate specificity, dependence on the stoichiometric use and costs of cofactors such asNADPH and the costs associated with BVMO's themselves because lengthy purification steps are required.In vivo oxidations with metabolically active microbial cells introduce complications on their own.In one study [cite journal | title = Towards practical biocatalytic Baeyer-Villiger reactions: applying a thermostable enzyme in the gram-scale synthesis of optically active lactones in a two-liquid-phase system | author = Frank Schulz; François Leca; Frank Hollmann; Manfred T Reetz | journal =
Beilstein Journal of Organic Chemistry | date = 2005 | volume = 1 | issue = 10 | url = http://bjoc.beilstein-journals.org/content/pdf/1860-5397-1-10.pdf | format = PDF | doi = 10.1186/1860-5397-1-10 | pages = 10 | pmid = 16542025] the enzyme purification issue is addressed and a special thermally stable monooxygenase is isolated from a specificE-coli strain. Thisenzyme convertsracemic 2-phenylcyclohexanone with oxygen to the corresponding (R)-lactone with 50%chemical yield and 94%enantiomeric excess with in a biphasic system of water andhexane . The NADPH cofactor is regenerated in eachcatalytic cycle by action of a seconddehydrogenase enzyme which consumesisopropanol as asacrificial catalyst . The solubility of the organic reactant and product is low in the aqueous phase thus averting inhibition. On the other hand thecatalytic turnover number for this reaction is much larger than can be obtained with classical organicasymmetric catalyst s.References
See also
*
Dakin reaction
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