The Baeyer-Villiger oxidation (also called Baeyer-Villiger rearrangement) is an organic reaction that forms an ester from a ketone or a lactone from a cyclic ketone. Peroxyacids or peroxides are used as the oxidant. The reaction is named after Adolf Baeyer and Victor Villiger who first reported the reaction in 1899.
- 1 Reaction mechanism
- 2 Historical background
- 3 Stereochemistry
- 4 Reagents
- 5 Limitations
- 6 Modifications
- 7 Applications
- 8 See also
- 9 References
- 10 External links
In the first step of the reaction mechanism, the peroxyacid protonates the oxygen of the carbonyl group. This makes the carbonyl group more susceptible to attack by the peroxyacid. In the next step of the reaction mechanism, the peroxyacid attacks the carbon of the carbonyl group forming what is known as the Criegee intermediate. Through a concerted mechanism, one of the substituents on the ketone migrates to the oxygen of the peroxide group while a carboxylic acid leaves. This migration step is thought to be the rate determining step. Finally, deprotonation of the oxygen of the carbonyl group produces the ester.
The products of the Baeyer-Villiger oxidation are believed to be controlled through both primary and secondary stereoelectronic effects. The primary stereoelectronic effect in the Baeyer-Villiger oxidation refers to the necessity of the oxygen-oxygen bond in the peroxide group to be antiperiplanar to the group that migrates. This orientation facilitates optimum overlap of the 𝛔 orbital of the migrating group to the 𝛔* orbital of the peroxide group. The secondary stereoelectronic effect refers to the necessity of the lone pair on the oxygen of the hydroxyl group to be antiperiplanar to the migrating group. This allows for optimum overlap of the oxygen nonbonding orbital with the 𝛔* orbital of the migrating group. This migration step is also (at least in silico) assisted by two or three peroxyacid units enabling the hydroxyl proton to shuttle to its new position.
The migratory ability is ranked tertiary ≻ secondary ≻ phenyl ≻ primary. Allylic groups also migrate better than primary groups but not as good as secondary groups. If there is an electron withdrawing group on the substituent, then it decreases the rate of migration. There are two explanations for this trend in migration ability. One explanation relies on the carbocation resonance structure of the Criegee intermediate. Keeping this structure in mind, it makes sense that the substituent that can maintain positive charge the best would be most likely to migrate. Tertiary groups are more stable carbocations than secondary groups, and secondary groups are more stable than primary. Therefore, the tertiary ≻ secondary ≻ primary trend is observed.
Another explanation uses stereoelectronic effects and steric bulk to explain the trend. As mentioned, the substituent that is antiperiplanar to the peroxide group in the transition state will be the group that migrates. This transition state has a gauche interaction between the peroxyacid and the non-migrating substituent. If the bulkier group is placed antiperiplanar to the peroxide group, the gauche interaction between the substituent on the forming ester and the carbonyl group of the peroxyacid will be reduced. Thus, it is the bulkier group that ends up antiperiplanar to the peroxide group making it the group that migrates. This explains the trend of tertiary ≻ secondary ≻ primary because tertiary groups are generally bulkier than secondary and primary groups.
In 1899, Adolf Baeyer and Victor Villiger first published a demonstration of the reaction that we now know as the Baeyer-Villiger oxidation. They used peroxymonosulfuric acid to make the corresponding lactones from camphor, menthone, and tetrahydrocarvone.
There were three suggested reaction mechanisms of the Baeyer-Villiger oxidation that seemed to fit with observed reaction outcomes. These three reaction mechanisms can really be split into two pathways of peroxyacid attack. The first pathway has the peroxyacid attack the oxygen of the carbonyl group. The second pathway has the peroxyacid attack the carbon of the carbonyl group. The first pathway could lead to two possible intermediates: Baeyer and Villiger suggested a dioxirane intermediate, while Georg Wittig and Gustav Pieper suggested a peroxide intermediate with no dioxirane formation. A second pathway was suggested by Rudolf Criegee. In this pathway, the peracid attacks the carbonyl carbon producing what is now known as the Criegee intermediate.
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 to label benzophenone. The three different mechanisms each lead to a different distribution of labelled products. The Criegee intermediate leads to a product that is only labelled on the oxygen of the carbonyl group. The product of the Wittig and Pieper intermediate is only labeled on the oxygen of the ester. The Baeyer and Villiger intermediate leads to a 1:1 distribution of both of the above products. The outcome of the labelling experiment supported the Criegee intermediate. It is now believed that the mechanism follows the Criegee intermediate.
Although many different peroxyacids are used for the Baeyer-Villiger oxidation, some of the more common oxidants include meta-chloroperbenzoic acid (mCPBA) and trifluoroperacetic acid (TFPAA). The reactivity differs depending on the choice of the peroxyacid. The general trend of reactivity correlates to the strength of the corresponding acid (or alcohol in the case of the peroxides). The stronger the acid, the more reactive will the corresponding peroxyacid be in performing the Baeyer-Villiger oxidation. The trend of reactivity of some reagents is TFPAA ≻ 4-nitroperbenzoic acid ≻ mCPBA and performic acid ≻ peracetic acid ≻ hydrogen peroxide ≻ tert-butyl hydroperoxide. The peroxides are much less reactive than the peroxyacids. In fact, hydrogen peroxide requires a catalyst in order to be used as an oxidant in the Baeyer-Villiger oxidation.
The use of peroxyacids and peroxides when performing the Baeyer-Villiger oxidation can cause the undesirable oxidation of other functional groups. Alkenes and amines are a few of the groups that can be oxidized. However, methods have been developed that will allow for the tolerance of these functional groups. For instance, if there is an alkene present in the ketone, the alkene could potentially undergo oxidation to the epoxide. In general, electron-poor alkenes will prefer the Baeyer-Villiger oxidation, while electron-rich will prefer the epoxidation. However, it may depend on the reagents that are used. For example, there are methods that will selectively choose the formation of the epoxide or the ester. In 1962, G. B. Payne reported that the use of hydrogen peroxide in the presence of a selenium catalyst will produce the epoxide, while use of peroxyacetic acid will form the ester.
Catalytic Baeyer-Villiger oxidation
There has been interest in making the Baeyer-Villiger oxidation work with hydrogen peroxide as an oxidant in the presence of a catalyst. Using hydrogen peroxide as an oxidant makes the reaction more environmentally friendly as the waste produced would just be water. The use of benzeneseleninic acid derivatives as a catalyst has been reported to give high selectivity with hydrogen peroxide as the oxidant.
Another way to create a catalytic Baeyer-Villiger oxidation is by using enzymes as the catalyst. Baeyer-Villiger monooxygenases (BVMOs) use dioxygen to perform the Baeyer-Villiger oxidation. These enzymes are capable of enantioselective oxidations of prochiral substrates.
Asymmetric Baeyer-Villiger oxidation
There have been attempts to use organometallic catalysts to perform an enatioselective Baeyer-Villiger oxidation.  The first reported instance of an asymmetric Baeyer-Villiger oxidation on a prochiral ketone used dioxygen as the oxidant and a copper catalyst. Other catalysts followed such as platinum and aluminum catalysts.
Zoapatanol is a biologically active molecule that occurs naturally in the zeopatle plant. The zeopatle plant has been used in Mexico to make a tea that can induce menstruation and labor. In 1981, Vinayak Kane and Donald Doyle reported a synthesis of zoapatanol. 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.
Steroids are an important class of molecules for use in therapeutics. For instance, testololactone has been identified as an anticancer agent. In 2013, Alina Świzdor reported the transformation of dehydroepiandrosterone to testololactone by use of a fungus that produces Baeyer-Villiger monooxygenases. The fungus formed testololactone from dehydroepiandrosterone via a Baeyer-Villiger oxidation.
- Kürti, László; Czakó, Barbara (2005). Strategic Applications of Named Reactions in Organic Synthesis. Burlington; San Diego; London: Elsevier Academic Press. p. 28. ISBN 978-0-12-369483-6.
- Krow, Grant R. (1993). "The Baeyer-Villiger Oxidation of Ketones and Aldehydes". Organic Reactions 43 (3): 251–798. doi:10.1002/0471264180.or043.03.
- Crudden, Cathleen M.; Chen, Austin C.; Calhoun, Larry A. (2000). "A Demonstration of the Primary Stereoelectronic Effect in the Baeyer-Villiger Oxidation of α-Fluorocyclohexanones". Angew. Chem. Int. Ed. 39 (16): 2851–2855. doi:10.1002/1521-3773(20000818)39:16<2851::aid-anie2851>3.0.co;2-y.
- Myers, Andrew G. "Chemistry 115 Handouts: Oxidation" (PDF).
- The Role of Hydrogen Bonds in Baeyer-Villiger Reactions Shinichi Yamabe and Shoko Yamazaki J. Org. Chem.; 2007; 72(8) pp 3031–41; (Article) doi:10.1021/jo0626562
- ten Brink, G.-J.; Arends, W. C. E.; Sheldon, R. A. (2004). "The Baeyer-Villiger Reaction: New Developments toward Greener Procedures". Chem. Rev. 104 (9): 4105–4123. doi:10.1021/cr030011l.
- Li, Jie Jack; Corey, E. J., eds. (2007). Name Reactions of Functional Group Transformations. Hoboken, NJ: Wiley-Interscience.
- Hawthorne, M. Frederick; Emmons, William D.; McCallum, K. S. (1958). "A Re-examination of the Peroxyacid Cleavage of Ketones. I. Relative Migratory Aptitudes". J. Am. Chem. Soc. 80 (23): 6393–6398. doi:10.1021/ja01556a057.
- Jones, Jr., Maitland; Fleming, Steven A. (2010). Organic Chemistry (4th ed.). Canada: W. W. Norton & Company. p. 293. ISBN 978-0-393-93149-5.
- Evans, D. A. "Stereoelectronic Effects-2" (PDF). Chemistry 206 (Fall 2006-2007).
- Baeyer, Adolf; Villiger, Victor (1899). "Einwirkung des Caro'schen Reagens auf Ketone". Ber. Dtsch. Chem. Ges. 32 (3): 3625–3633. doi:10.1002/cber.189903203151.
- Hassall, C. H. (1957). "The Baeyer-Villiger Oxidation of Aldehydes and Ketones". Organic Reactions 9 (3): 73–106. doi:10.1002/0471264180.or009.03.
- Renz, Michael; Meunier, Bernard (1999). "100 Years of Baeyer-Villiger Oxidations". Eur. J. Org. Chem. 1999 (4): 737–750. doi:10.1002/(SICI)1099-0690(199904)1999:4<737::AID-EJOC737>3.0.CO;2-B.
- Doering, W. von E.; Dorfman, Edwin (1953). "Mechanism of the Peracid Ketone-Ester Conversion. Analysis of Organic Compounds for Oxygen-18". J. Am. Chem. Soc. 75 (22): 5595–5598. doi:10.1021/ja01118a035.
- Doering, W. von E.; Speers, Louise (1950). "The Peracetic Acid Cleavage of Unsymmetrical Ketones" 72 (12). pp. 5515–5518. doi:10.1021/ja01168a041.
- Turner, Richard B. (1950). "Stereochemistry of the Peracid Oxidation of Ketones". J. Am. Chem. Soc. 72 (2): 878–882. doi:10.1021/ja01158a061.
- Gallagher, T. F.; Kritchevsky, Theodore H. (1950). "Perbenzoic Acid Oxidation of 20-Ketosteroids and the Stereochemistry of C-17". J. Am. Chem. Soc. 72 (2): 882–885. doi:10.1021/ja01158a062.
- Cavarzan, Alessandra; Scarso, Alessandro; Sgarbossa, Paolo; Michelin, Rino A.; Strukul, Giorgio (2010). "Green Catalytic Baeyer–Villiger Oxidation with Hydrogen Peroxide in Water Mediated by Pt(II) Catalysts". ChemCatChem 2 (10): 1296–1302. doi:10.1002/cctc.201000088.
- Grant R. Krow (1991). Trost, Barry M.; Fleming, Ian, eds. Comprehensive Organic Synthesis - Selectivity, Strategy and Efficiency in Modern Organic Chemistry, Volumes 1 - 9. Elsevier. pp. 671–688. ISBN 978-0-08-035930-4.
- Seymour, Craig. "Page 1 The Asymmetric Baeyer-Villiger Oxidation". http://www.scs.illinois.edu/denmark/presentations/2013/gm-2013-7-16.pdf.
- Payne, G. B. (1962). "A Simplified Procedure for Epoxidation by Benzonitrile-Hydrogen Peroxide. Selective Oxidation of 2-Allylcyclohexanone". Tetrahedron 18 (6): 763–765. doi:10.1016/S0040-4020(01)92726-7.
- ten Brink, Gerd-Jan; Vis, Jan-Martijn; Arends, Isabel W. C. E.; Sheldon, Roger A. (2001). "Selenium-Catalyzed Oxidations with Aqueous Hydrogen Peroxide. 2. Baeyer−Villiger Reactions in Homogeneous Solution". J. Org. Chem. 66 (7): 2429–2433. doi:10.1021/jo0057710.
- Levine, Seymour D.; Adams, Richard E.; Chen, Robert; Cotter, Mary Lou; Hirsch, Allen F.; Kane, Vinayak V.; Kanojia, Ramesh M.; Shaw, Charles; Wachter, Michael P.; Chin, Eva; Huettemann, Richard; Ostrowski, Paul (1979). "Zoapatanol and Montanol, Novel Oxepane Diterpenoids, from the Mexican Plant Zoapatle (Montanoa tomentosa)". J. Am. Chem. Soc. 101 (12): 3405–3407. doi:10.1021/ja00506a057.
- Kane, Vinayak V.; Doyle, Donald L. (1981). "Total Synthesis of (±) Zoapatanol: A Stereospecific Synthesis of a Key Intermediate". Tetrahedron Lett. 22 (32): 3027–3030. doi:10.1016/S0040-4039(01)81818-9.
- Kane, Vinayak V.; Doyle, Donald L. (1981). "Total Synthesis of (±) Zoapatanol". Tetrahedron Lett. 22 (32): 3031–3034. doi:10.1016/S0040-4039(01)81819-0.
- Świzdor, Alina (2013). "Baeyer-Villiger Oxidation of Some C19 Steroids by Penicillium lanosocoeruleum". Molecules 18 (11): 13812–13822. doi:10.3390/molecules181113812.
Lua error in Module:Authority_control at line 346: attempt to index field 'wikibase' (a nil value).