Baeyer–Villiger oxidation

Last updated

Contents

Baeyer-Villiger oxidation
Named after Adolf von Baeyer
Victor Villiger
Reaction type Organic redox reaction
Reaction
Ketone
+
RCO3H or mCPBA
↓
Ester or Lactone
Identifiers
Organic Chemistry Portal baeyer-villiger-oxidation
RSC ontology ID RXNO:0000031

The Baeyer–Villiger oxidation is an organic reaction that forms an ester from a ketone or a lactone from a cyclic ketone, using peroxyacids or peroxides as the oxidant. [1] The reaction is named after Adolf von Baeyer and Victor Villiger who first reported the reaction in 1899. [1]

Baeyer-Villiger oxidation Baeyer-Villiger oxidation.svg
Baeyer-Villiger oxidation

Reaction mechanism

In the first step of the reaction mechanism, the peroxyacid protonates the oxygen of the carbonyl group. [1] This makes the carbonyl group more susceptible to be attacked by the peroxyacid. [1] Next, the peroxyacid attacks the carbon of the carbonyl group forming what is known as the Criegee intermediate. [1] Through a concerted mechanism, one of the substituents on the ketone group migrates to the oxygen of the peroxide group while a carboxylic acid leaves. [1] This migration step is thought to be the rate determining step. [2] [3] Finally, deprotonation of the oxocarbenium ion produces the ester. [1]

Reaction mechanism of the Baeyer-Villiger oxidation. Baeyer-Villiger oxidation reaction mechanism.svg
Reaction mechanism of the Baeyer-Villiger oxidation.

The products of the Baeyer–Villiger oxidation are believed to be controlled through both primary and secondary stereoelectronic effects. [4] 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. [4] [3] This orientation facilitates optimum overlap of the 𝛔 orbital of the migrating group to the 𝛔* orbital of the peroxide group. [1] 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. [4] This allows for optimum overlap of the oxygen nonbonding orbital with the 𝛔* orbital of the migrating group. [5] 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. [6]

Stereoelectronic effects Baeyer-Villiger oxidation stereoelectronic effects.svg
Stereoelectronic effects

The migratory ability is ranked tertiary > secondary > aryl > primary. [7] Allylic groups are more apt to migrate than primary alkyl groups but less so than secondary alkyl groups. [5] Electron-withdrawing groups on the substituent decrease the rate of migration. [8] There are two explanations for this trend in migration ability. [9] One explanation relies on the buildup of positive charge in the transition state for breakdown of the Criegee intermediate (illustrated by the carbocation resonance structure of the Criegee intermediate). [9] Keeping this structure in mind, it makes sense that the substituent that can maintain positive charge the best would be most likely to migrate. [9] The higher the degree of substitution, the more stable a carbocation generally is. [10] Therefore, the tertiary > secondary > primary trend is observed.

Resonance structures of the Criegee intermediate Criegee intermediate resonance structures.svg
Resonance structures of the Criegee intermediate

Another explanation uses stereoelectronic effects and steric arguments. [11] As mentioned, the substituent that is antiperiplanar to the peroxide group in the transition state will migrate. [4] This transition state has a gauche interaction between the peroxyacid and the non-migrating substituent. [11] 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. [11] Thus, it is the bulkier group that will prefer to be antiperiplanar to the peroxide group, enhancing its aptitude for migration. [11]

Steric bulk influencing migration Criegee intermediate stereoelectronics.svg
Steric bulk influencing migration

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]

The migration does not change the stereochemistry of the group that transfers, i.e.: it is stereoretentive. [13] [14]

History

Oxidation of camphor as reported by Baeyer and Villiger. Original Baeyer-Villiger oxidation reactions (cropped).png
Oxidation of camphor as reported by Baeyer and Villiger.

In 1899, Adolf Baeyer and Victor Villiger demonstrated the reaction now known as the Baeyer–Villiger oxidation. [15] [16] They used peroxymonosulfuric acid to make the corresponding lactones from camphor, menthone, and tetrahydrocarvone. [16] [17]

Three reaction mechanisms were suggested. [18] These three reaction mechanisms can really be split into two pathways of peroxyacid attack – on either the oxygen or the carbon of the carbonyl group. [19] Attack on oxygen could lead to two possible intermediates: Baeyer and Villiger suggested a dioxirane intermediate, while Georg Wittig and Gustav Pieper suggested a peroxide with no dioxirane formation. [19] Carbon attack was suggested by Rudolf Criegee. [19] In this pathway, the peracid attacks the carbonyl carbon, producing what is now known as the Criegee intermediate. [19]

Proposed Baeyer-Villiger oxidation intermediates Proposed Baeyer Villiger Intermediates (cropped).png
Proposed Baeyer-Villiger oxidation intermediates

In 1953, William von Eggers Doering and Edwin Dorfman identified the mechanism by using oxygen-18-labelling of benzophenone. [18] The three previously suggested 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. [18] The product of the Wittig and Pieper intermediate is only labeled on the alkoxy group of the ester. [18] The Baeyer and Villiger intermediate leads to a 1:1 distribution of both of the above products. [18] The outcome of the labelling experiment supported the Criegee intermediate, [18] which is now the generally accepted pathway. [1]

The different possible outcomes of Dorfman and Doering's labelling experiment Dorfman and Doering's Labelling Experiment.png
The different possible outcomes of Dorfman and Doering's labelling experiment

Reagents

Among the many peroxyacids used for the Baeyer–Villiger oxidation, common oxidants include meta-chloroperbenzoic acid (mCPBA) and trifluoroperacetic acid (TFPAA). [2] The general trend is that higher reactivity is correlated with lower pKa (i.e.: stronger acidity) of the corresponding carboxylic acid (or alcohol in the case of the peroxides). [7] Therefore, the reactivity trend shows TFPAA > 4-nitroperbenzoic acid > mCPBA and performic acid > peracetic acid > hydrogen peroxide > tert-butyl hydroperoxide. [5] Hydroperoxides are much less reactive than the peroxyacids. [2] The use of hydrogen peroxide even requires a catalyst. [7] [20] In addition, using organic peroxides and hydrogen peroxide often promotes side-reactions. [21] Oxygen can be used to convert cyclohexanol to caprolactone, but the process generates hydrogen peroxide in situ: [7]

C6H11OH + O2 → C6H10O + H2O2
C6H10O + H2O2 → C6H10O2 + H2O

Limitations

Two outcomes for peroxide oxidation Reagent Dependent Oxidation.png
Two outcomes for peroxide oxidation

The use of peroxyacids and peroxides when performing the Baeyer–Villiger oxidation can oxidize other functional groups. [23] For instance, electron-rich alkenes may oxidize to epoxides. [23]

Modifications

Catalytic Baeyer-Villiger oxidation

The use of hydrogen peroxide as an oxidant would make the reaction more environmentally friendly. [7] Benzeneseleninic acid derivatives as catalysts have been reported to give high selectivity with hydrogen peroxide as the oxidant. [7] Another promising class of catalysts are solid Lewis acid catalysts such as stannosilicates. [24]

Asymmetric Baeyer-Villiger oxidation

There have been attempts to use organometallic catalysts to perform enantioselective Baeyer–Villiger oxidations. [7] The first reported instance of one such oxidation of a prochiral ketone used dioxygen as the oxidant with a copper catalyst. [25] Other catalysts, including platinum and aluminum compounds, followed. [25]

Baeyer-Villiger monooxygenases

Reaction mechanism of the flavin cofactor to catalyse the Baeyer-Villiger reaction in Baeyer-Villiger monooxygenase enzymes. BVMO reaction mechanism.png
Reaction mechanism of the flavin cofactor to catalyse the Baeyer-Villiger reaction in Baeyer-Villiger monooxygenase enzymes.

In nature, enzymes called Baeyer-Villiger monooxygenases (BVMOs) perform the oxidation analogously to the chemical reaction. [26] To facilitate this chemistry, BVMOs contain a flavin adenine dinucleotide (FAD) cofactor. [27] In the catalytic cycle (see figure on the right), the cellular redox equivalent NADPH first reduces the cofactor, which allows it subsequently to react with molecular oxygen. The resulting peroxyflavin is the catalytic entity oxygenating the substrate, and theoretical studies suggest that the reaction proceeds through the same Criegee intermediate as observed in the chemical reaction. [28] After the rearrangement step forming the ester product, a hydroxyflavin remains, which spontaneously eliminates water to form oxidized flavin, thereby closing the catalytic cycle.

BVMOs are closely related to the flavin-containing monooxygenases (FMOs), [29] enzymes that also occur in the human body, functioning within the frontline metabolic detoxification system of the liver along the cytochrome P450 monooxygenases. [30] 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. [31]

BVMOs have been widely studied due to their potential as biocatalysts, that is, for an application in organic synthesis. [32] Considering the environmental concerns for most of the chemical catalysts, the use of enzymes is considered a greener alternative. [26] 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), [33] 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. [34] [35] 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. [26] [32]

Illustrations

Use of Baeyer-Villiger oxidation en route to zoapatanol. Synthesis of Zoapatanol (cropped).png
Use of Baeyer-Villiger oxidation en route to zoapatanol.

Zoapatanol (from the zeopatle plant, has been prepared by the Baeyer–Villiger oxidation to make a lactone. [36] [37]

The steroid dehydroepiandrosterone converts to the anticancer agent testololactone induced by fungus that produces Baeyer-Villiger monooxygenases. [38]

Swizdor reported that a Baeyer-Villiger monooxygenase could change dehydroepiandrosterone into testololactone Dehydroepiandrosterone to testololactone.png
Świzdor reported that a Baeyer-Villiger monooxygenase could change dehydroepiandrosterone into testololactone

See also

References

  1. 1 2 3 4 5 6 7 8 9 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.
  2. 1 2 3 Krow, Grant R. (1993). "The Baeyer-Villiger Oxidation of Ketones and Aldehydes". Organic Reactions. 43 (3): 251–798. doi:10.1002/0471264180.or043.03. ISBN   0471264180.
  3. 1 2 Carey, Francis A.; Sundberg, Richard J. (2007). Advanced Organic Chemistry: Part B: Reactions and Synthesis (5th ed.). New York: Springer. p. 1135. ISBN   978-0387683546.
  4. 1 2 3 4 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. PMID   11027987.
  5. 1 2 3 Myers, Andrew G. "Chemistry 115 Handouts: Oxidation" (PDF). Harvard University.
  6. ↑ Yamabe, Shinichi (2007). "The Role of Hydrogen Bonds in Baeyer−Villiger Reactions". The Journal of Organic Chemistry. 72 (8): 3031–3041. doi:10.1021/jo0626562. PMID   17367197.
  7. 1 2 3 4 5 6 7 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. PMID   15352787.
  8. ↑ Li, Jie Jack; Corey, E. J., eds. (2007). Name Reactions of Functional Group Transformations. Hoboken, NJ: Wiley-Interscience.
  9. 1 2 3 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.
  10. ↑ Jones, Jr., Maitland; Fleming, Steven A. (2010). Organic Chemistry (4th ed.). Canada: W. W. Norton & Company. p.  293. ISBN   978-0-393-93149-5.
  11. 1 2 3 4 Evans, D. A. "Stereoelectronic Effects-2". Chemistry 206 (Fall 2006-2007).
  12. ↑ Sanyal, S.N. (2003). Reactions, Rearrangements and Reagents (4 ed.). p. 90. ISBN   978-81-7709-605-7.
  13. ↑ Turner, Richard B. (1950). "Stereochemistry of the Peracid Oxidation of Ketones". J. Am. Chem. Soc. 72 (2): 878–882. doi:10.1021/ja01158a061.
  14. ↑ 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.
  15. ↑ 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.
  16. 1 2 Hassall, C. H. (1957). "The Baeyer-Villiger Oxidation of Aldehydes and Ketones". Organic Reactions. 9 (3): 73–106. doi:10.1002/0471264180.or009.03. ISBN   0471264180.
  17. ↑ 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.
  18. 1 2 3 4 5 6 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.
  19. 1 2 3 4 Doering, W. von E.; Speers, Louise (1950). "The Peracetic Acid Cleavage of Unsymmetrical Ketones". Journal of the American Chemical Society. 72 (12): 5515–5518. doi:10.1021/ja01168a041.
  20. ↑ 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. S2CID   98508888.
  21. ↑ Schweitzer-Chaput, Bertrand; Kurtén, Theo; Klussmann, Martin (2015). "Acid-Mediated Formation of Radicals or Baeyer-Villiger Oxidation from Criegee Adducts". Angewandte Chemie International Edition. 54 (40): 11848–11851. doi:10.1002/anie.201505648. PMID   26267787.
  22. ↑ 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.
  23. 1 2 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.
  24. ↑ Ferrini, Paola; Dijkmans, Jan; Clercq, Rik De; Vyver, Stijn Van de; Dusselier, Michiel; Jacobs, Pierre A.; Sels, Bert F. (2017). "Lewis acid catalysis on single site Sn centers incorporated into silica hosts". Coordination Chemistry Reviews. 343: 220–255. doi:10.1016/j.ccr.2017.05.010.
  25. 1 2 Seymour, Craig. "Page 1 The Asymmetric Baeyer-Villiger Oxidation" (PDF). scs.illinois.edu.
  26. 1 2 3 Leisch, Hannes; Morley, Krista; Lau, Peter C. K. (13 July 2011). "Baeyer−Villiger Monooxygenases: More Than Just Green Chemistry". Chemical Reviews. 111 (7): 4165–4222. doi:10.1021/cr1003437. ISSN   0009-2665. PMID   21542563.
  27. ↑ Sheng, Dawei; Ballou, David P.; Massey, Vincent (1 September 2001). "Mechanistic Studies of Cyclohexanone Monooxygenase: Chemical Properties of Intermediates Involved in Catalysis". Biochemistry. 40 (37): 11156–11167. doi:10.1021/bi011153h. ISSN   0006-2960. PMID   11551214.
  28. ↑ Polyak, Iakov; Reetz, Manfred T.; Thiel, Walter (8 February 2012). "Quantum Mechanical/Molecular Mechanical Study on the Mechanism of the Enzymatic Baeyer–Villiger Reaction". Journal of the American Chemical Society. 134 (5): 2732–2741. doi:10.1021/ja2103839. ISSN   0002-7863. PMID   22239272.
  29. ↑ van Berkel, W. J. H.; Kamerbeek, N. M.; Fraaije, M. W. (5 August 2006). "Flavoprotein monooxygenases, a diverse class of oxidative biocatalysts". Journal of Biotechnology. 124 (4): 670–689. doi:10.1016/j.jbiotec.2006.03.044. hdl: 11370/99a1ac5c-d4a4-4612-90a3-4fe1d4d03a11 . ISSN   0168-1656. PMID   16712999.
  30. ↑ Iyanagi, Takashi (1 January 2007). "Molecular Mechanism of Phase I and Phase II Drug-Metabolizing Enzymes: Implications for Detoxification". International Review of Cytology. 260. Academic Press: 35–112. doi:10.1016/S0074-7696(06)60002-8. ISBN   9780123741141. PMID   17482904.
  31. ↑ Fiorentini, Filippo; Geier, Martina; Binda, Claudia; Winkler, Margit; Faber, Kurt; Hall, Mélanie; Mattevi, Andrea (15 April 2016). "Biocatalytic Characterization of Human FMO5: Unearthing Baeyer–Villiger Reactions in Humans". ACS Chemical Biology. 11 (4): 1039–1048. doi:10.1021/acschembio.5b01016. ISSN   1554-8929. PMID   26771671.
  32. 1 2 Fürst, Maximilian J. L. J.; Gran-Scheuch, Alejandro; Aalbers, Friso S.; Fraaije, Marco W. (6 December 2019). "Baeyer–Villiger Monooxygenases: Tunable Oxidative Biocatalysts". ACS Catalysis. 9 (12): 11207–11241. doi: 10.1021/acscatal.9b03396 .
  33. ↑ Fürst, Maximilian J. L. J.; Romero, Elvira; Gómez Castellanos, J. Rúben; Fraaije, Marco W.; Mattevi, Andrea (7 December 2018). "Side-Chain Pruning Has Limited Impact on Substrate Preference in a Promiscuous Enzyme". ACS Catalysis. 8 (12): 11648–11656. doi: 10.1021/acscatal.8b03793 . PMC   6345240 . PMID   30687578.
  34. ↑ Fürst, Maximilian J. L. J.; Boonstra, Marjon; Bandstra, Selle; Fraaije, Marco W. (2019). "Stabilization of cyclohexanone monooxygenase by computational and experimental library design". Biotechnology and Bioengineering. 116 (9): 2167–2177. doi: 10.1002/bit.27022 . ISSN   1097-0290. PMC   6836875 . PMID   31124128.
  35. ↑ Li, Guangyue; Garcia-Borràs, Marc; Fürst, Maximilian J. L. J.; Ilie, Adriana; Fraaije, Marco W.; Houk, K. N.; Reetz, Manfred T. (22 August 2018). "Overriding Traditional Electronic Effects in Biocatalytic Baeyer–Villiger Reactions by Directed Evolution". Journal of the American Chemical Society. 140 (33): 10464–10472. doi:10.1021/jacs.8b04742. ISSN   0002-7863. PMC   6314816 . PMID   30044629.
  36. ↑ 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.
  37. ↑ 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.
  38. ↑ Świzdor, Alina (2013). "Baeyer-Villiger Oxidation of Some C19 Steroids by Penicillium lanosocoeruleum". Molecules. 18 (11): 13812–13822. doi: 10.3390/molecules181113812 . PMC   6270215 . PMID   24213656.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.