Baeyer-Villiger Oxidation Reaction

The Baeyer–Villiger reaction involves the oxidation of ketones to esters by C-C bond cleavage of the carbonyl group and the introduction of an oxygen atom adjacent to it.¹ This reaction can be accomplished using hydrogen peroxide, 3-chloroperbenzoic acid (m-chloroperoxybenzoic acid), peroxyacetic acid, or peroxytrifluoroacetic acid as the oxidizing agent. This reaction is also useful in the synthesis of lactones (cyclic esters) from cyclic ketones.

Section Overview

• Precautions
• Applications
• Recent Research and Trends
• References

Stereospecificity and predictable regiochemistry are important features of the Baeyer–Villiger oxidation reaction. The reaction is regiospecific in nature and depends on the relative migration ability of the substituents attached to the carbonyl group. This reaction was described by Adolf von Baeyer and Victor Villiger in 1899.

An example for Baeyer–Villiger oxidation reaction:

Precautions

Please consult the Safety Data Sheet for information regarding hazards and safe handling practices.

Applications

The Baeyer–Villiger oxidation reaction is useful for the following studies:

• Synthesis of lactones from mesomeric cyclohexanones.²
• Synthesis of 3-hydroxyindole-2-carboxylates.³
• Conversion of non-activated [¹⁸F]fluorobenzaldehydes to [¹⁸F]fluorophenols with high radiochemical yield.⁴
• Synthesis of dibenzo-18-crown-6, dibenzo-21-crown-7, and dihydroxydibenzo-18-crown-6.⁵
• One-pot chemoenzymatic synthesis of g-butyrolactones.⁶
• Metal-free synthesis of vinyl acetates.⁷

Recent Research and Trends

• The Baeyer–Villiger oxidation of cyclic ketones using aqueous hydrogen peroxide as an oxidant over transition metal oxides yields the corresponding lactones.⁸
• Silica-supported tricobalt tetraoxide (Co₃O₄/SiO₂) catalysts have been employed for the Baeyer–Villiger oxidation of cyclohexanone under Mukaiyama conditions.⁹
• Submicrometer-sized tin-containing MCM-41 particles with a size of several hundred nanometers were reported as selective catalysts for the Baeyer–Villiger oxidation of adamantanone with aqueous H₂O₂.¹⁰
• Chemoenzymatic Baeyer–Villiger oxidation of cyclic ketones catalyzed by Candida antarctica lipase B or Novozyme-435 suspended in an ionic liquid has been studied.¹¹
• Kinetic resolution of racemic 2-substituted cyclopentanones has been achieved via highly regio- and enantioselective Baeyer–Villiger oxidation.¹²

Limitations of Baeyer-Villiger Oxidation:

The Baeyer-Villiger reaction, while useful, has several limitations:

• The reaction is generally limited to ketones; some ketones may not react efficiently or at all, particularly sterically hindered ones.
• Although the reaction can exhibit regioselectivity, predicting the predominant product can be challenging, especially with complex substrates, leading to unwanted by-products.
• The reaction conditions, such as temperature and solvent, can significantly affect the outcome, requiring careful optimization for each substrate.
• The use of peracids (such as peracetic acid) can lead to decomposition or side reactions, complicating the reaction and affecting yields.
• The reaction may produce undesirable by-products, requiring additional purification steps to isolate the desired ester or lactone.

References

1. Yachnin BJ, Sprules T, McEvoy MB, Lau PCK, Berghuis AM. 2012. The Substrate-Bound Crystal Structure of a Baeyer?Villiger Monooxygenase Exhibits a Criegee-like Conformation. J. Am. Chem. Soc.. 134(18):7788-7795. https://doi.org/10.1021/ja211876p

2. Taschner MJ, Black DJ. 1988. The enzymatic Baeyer-Villiger oxidation: enantioselective synthesis of lactones from mesomeric cyclohexanones. J. Am. Chem. Soc.. 110(20):6892-6893. https://doi.org/10.1021/ja00228a053

3. Hickman ZL, Sturino CF, Lachance N. 2000. A concise synthesis of 3-hydroxyindole-2-carboxylates by a modified Baeyer?Villiger oxidation. Tetrahedron Letters. 41(43):8217-8220. https://doi.org/10.1016/s0040-4039(00)01456-8

4. Castillo Meleán J, Ermert J, Coenen H. 2014. [18F]Fluorophenols from non-activated [18F]fluorobenzaldehydes by Baeyer-Villiger oxidation. J Nucl Med. 55(1):155.

5. Utekar DR, Saman SD. 2014. Application of Bayer-Villiger Reaction to the Synthesis of Dibenzo-18-crown-6, Dibenzo-21-crown-7 and Dihydroxydibenzo-18-crown-6. Journal of the Korean Chemical Society. 58(2):193-197. https://doi.org/10.5012/jkcs.2014.58.2.193

6. González-Martínez D, Rodríguez-Mata M, Méndez-Sánchez D, Gotor V, Gotor-Fernández V. 2015. Lactonization reactions through hydrolase-catalyzed peracid formation. Use of lipases for chemoenzymatic Baeyer?Villiger oxidations of cyclobutanones. Journal of Molecular Catalysis B: Enzymatic. 11431-36. https://doi.org/10.1016/j.molcatb.2014.09.002

7. Poladura B, Martínez-Castañeda Á, Rodríguez-Solla H, Llavona R, Concellón C, del Amo V. 2013. General Metal-Free Baeyer?Villiger-Type Synthesis of Vinyl Acetates. Org. Lett.. 15(11):2810-2813. https://doi.org/10.1021/ol401143q

8. Ma Q, Xing W, Xu J, Peng X. 2014. Baeyer?Villiger oxidation of cyclic ketones with aqueous hydrogen peroxide catalyzed by transition metal oxides. Catalysis Communications. 535-8. https://doi.org/10.1016/j.catcom.2014.04.017

9. Zang J, Ding Y, Pei Y, Liu J, Lin R, Yan L, Liu T, Lu Y. 2014. Efficient Co3O4/SiO2 catalyst for the Baeyer?Villiger oxidation of cyclohexanone. Reac Kinet Mech Cat. 112(1):159-171. https://doi.org/10.1007/s11144-014-0687-1

10. Chen N, Jiang Y, Cheng W, Lin K, Xu X. 2015. Synthesis of submicrometer-sized Sn-MCM-41 particles and their catalytic performance in Baeyer-Villiger oxidation. Chem. Res. Chin. Univ.. 31(1):138-143. https://doi.org/10.1007/s40242-014-4204-x

11. Drod A, Erfurt K, Bielas R, Chrobok A. Chemo-enzymatic Baeyer-Villiger oxidation in the presence of Candida antarctica lipase B and ionic liquids. New J. Chem.. 39(2):1315-1321. https://doi.org/10.1039/c4nj01976h

12. Zhou L, Liu X, Ji J, Zhang Y, Wu W, Liu Y, Lin L, Feng X. 2014. Regio- and Enantioselective Baeyer?Villiger Oxidation: Kinetic Resolution of Racemic 2-Substituted Cyclopentanones. Org. Lett.. 16(15):3938-3941. https://doi.org/10.1021/ol501737a