Organoselenium‐Catalyzed Baeyer–Villiger Oxidation of α,β‐Unsaturated Ketones by Hydrogen Peroxide to Access Vinyl Esters

By carefully screening the organoselenium pre‐catalysts and optimizing the reaction conditions, simple dibenzyl diselenide was found to be the best pre‐catalyst for Baeyer–Villiger oxidation of (E)‐α,β‐unsaturated ketones with the green oxidant hydrogen peroxide at room temperature. The organoselenium catalyst used in this reaction could be recycled and reused several times. This new method was suitable not only for methyl unsaturated ketones, but also for alkyl and aryl unsaturated ketones. Therefore, it provided a direct, mild, practical, highly functional group‐tolerant process for the chemoselective preparation of the versatile (E)‐vinyl esters from the readily available (E)‐α,β‐unsaturated ketones. A possible mechanism was also proposed to rationalize the activity of the organoselenium catalyst in the presence of hydrogen peroxide in this Baeyer–Villiger oxidation reaction.

     

A flavoprotein monooxygenase that catalyses a Baeyer-Villiger reaction and thioether oxidation using NADH as the nicotinamide cofactor

A gene from the marine bacterium Stenotrophomonas maltophilia encodes a 38.6 kDa FAD‐containing flavoprotein (Uniprot B2FLR2) named S. maltophilia flavin‐containing monooxygenase (SMFMO), which catalyses the oxidation of thioethers and also the regioselective Baeyer–Villiger oxidation of the model substrate bicyclo[3.2.0]hept‐2‐en‐6‐one. The enzyme was unusual in its ability to employ either NADH or NADPH as nicotinamide cofactor. The K_M and k_cat values for NADH were 23.7±9.1 μM and 0.029 s^?1 and 27.3±5.3 μM and 0.022 s^?1 for NADPH. However, k_cat/K_M value for the ketone substrate in the presence of 100 μM cofactor was 17 times greater for NADH than for NADPH. SMFMO catalysed the quantitative conversion of 5 mM ketone in the presence of substoichiometric concentrations of NADH with the formate dehydrogenase cofactor recycling system, to give the 2‐oxa and 3‐oxa lactone products of Baeyer–Villiger reaction in a ratio of 5:1, albeit with poor enantioselectivity. The conversion with NADPH was 15 %. SMFMO also catalysed the NADH‐dependent transformation of prochiral aromatic thioethers, giving in the best case, 80 % ee for the transformation of p‐chlorophenyl methyl sulfide to its R enantiomer. The structure of SMFMO reveals that the relaxation in cofactor specificity appears to be accomplished by the substitution of an arginine residue, responsible for recognition of the 2′‐phosphate on the NADPH ribose in related NADPH‐dependent FMOs, with a glutamine residue in SMFMO. SMFMO is thus representative of a separate class of single‐component, flavoprotein monooxygenases that catalyse NADH‐dependent oxidations from which possible sequences and strategies for developing NADH‐dependent biocatalysts for asymmetric oxygenation reactions might be identified.     

Aureobasidium subglaciale F134 is a bifunctional whole-cell biocatalyst for Baeyer–Villiger oxidation or selective carbonyl reduction controllable by temperature

The microbial production of either ester/lactones or enantio-enriched alcohols through Baeyer–Villiger oxidation or stereoselective reduction of ketones, respectively, is possible by using whole cells of A. subglaciale F134 as a bifunctional biocatalyst. The chemoselective pattern of acetophenone biotransformation catalyzed by these cells can be regulated through reaction temperature, directing the reaction either towards oxidation or reduction products. The Baeyer–Villiger oxidation activity of A. subglaciale F134 whole cells is particularly dependent on reaction temperature. Acetophenone was transformed efficiently to phenol via the primary Baeyer–Villiger product phenyl acetate at 20 °C after 48 h with 100% conversion. In contrast, at 35 °C, enantio-enriched (S)-1-phenylethanol was obtained as the sole product with 64% conversion and 89% ee. In addition, A. subglaciale F134 cells also catalyze the selective reduction of various structurally different aldehydes and ketones to alcohols with 40% to 100% yield, indicating broad substrate spectrum and good enantioselectivity in relevant cases. Our study provides a bifunctional biocatalyst system that can be used in Baeyer–Villiger oxidation as well as in asymmetric carbonyl reduction, setting the stage for future work concerning the identification and isolation of the respective enzymes.     

Supported Sulfonic Acid as Green and Efficient Catalyst for Baeyer–Villiger Oxidation with 30% Aqueous Hydrogen Peroxide

Silica‐supported propylsulfonic acid is a very good heterogeneous catalyst for the Baeyer–Villiger oxidation of cyclic ketones to lactones with stoichiometric 30% aqueous hydrogen peroxide in 1,1,1,3,3,3‐hexafluoro‐2‐propanol as solvent.     

C3‐Symmetric Titanium(IV) Triphenolate Amino Complexes for a Fast and Effective Oxidation of Secondary Amines to Nitrones with Hydrogen Peroxide

The efficient catalytic oxidation of secondary amines to nitrones using hydrogen peroxide as primary oxidant is described. The titanium(IV) complex 2 bearing a C₃‐symmetrical triphenolate amino ligand has proved to be an air‐ and water‐tolerant complex that efficiently catalyzes secondary amine oxidations at 60 °C without previous activation [catalyst loading as low as 0.01%, yields up to 99%, turnover numbers (TONs) up to 8000 and turnover frequencies (TOFs) up to 11000 h⁻¹).     

Pyrazinium Salts as Efficient Organocatalysts of Mild Oxidations with Hydrogen Peroxide

A series of 3‐substituted pyrazinium tetrafluoroborates was prepared as simple analogues of flavinium salts which are efficient organocatalysts for oxidations with hydrogen peroxide. It was shown that pyrazinium derivatives with an electron‐withdrawing substituent catalyze mild oxidations of sulfides to sulfoxides and Baeyer–Villiger oxidations in a similar way to flavinium catalysts. The most reactive catalyst, 3‐cyanopyrazinium tetrafluoroborate, was efficiently employed in preparative sulfoxidations of aromatic and aliphatic sulfides as well as in Baeyer–Villiger oxidations of cyclobutanones. A proposed mechanism for the catalysis is based on the formation of pyrazine hydroperoxide which is the agent oxidizing the substrate.     

A New Type of Stereoselectivity in Baeyer–Villiger Reactions: Access to E‐ and Z‐Olefins

A new concept for accessing configurationally defined trisubstituted olefins has been developed. Starting from a common ketone precursor of the type 4‐ethylidenecyclohexanone, Baeyer–Villiger monooxygenases are employed as catalysts in diastereoselective Baeyer–Villiger reactions leading to the corresponding E‐ or Z‐configurated lactones. Wild‐type cyclohexanone monooxygenase (CHMO) as catalyst delivers the E‐isomers and a directed evolution mutant the opposite Z‐isomers. Subsequent transition metal‐catalyzed chemical transformations of a key product containing a vinyl bromide moiety provide a variety of different trisubstituted E‐ or Z‐olefins. A model based on QM/MM sheds light on the origin of this unusual type of diastereoselectivity. In contrast to this biocatalytic approach, traditional Baeyer–Villiger reagents such as m‐CPBA fail to show any selectivity, 1:1 mixtures of E‐ and Z‐olefins being formed.     

Clean Baeyer–Villiger Oxidation Using Hydrogen Peroxide as Oxidant Catalyzed by Aluminium Trichloride in Ethanol

Baeyer–Villiger oxidation of ketones was carried out using AlCl₃ as catalyst, H₂O₂ (30%) as oxidant in innocuity and environmentally friendly ethanol conditions. Cyclic ketones and acyclic ketones were transformed into the corresponding lactones or esters in 5–24 h at 40–70 °C with very high conversion and selectivity. A possible reaction mechanism was also given.     

Direct Access to Medium‐Chain α,ω‐Dicarboxylic Acids by Using a Baeyer–Villiger Monooxygenase of Abnormal Regioselectivity

Baeyer–Villiger monooxygenases (BVMOs) are versatile biocatalysts in organic synthesis that can generate esters or lactones by inserting a single oxygen atom adjacent to a carbonyl moiety. The regioselectivity of BVMOs is essential in determining the ratio of two regioisomers for converting asymmetric ketones. Herein, we report a novel BVMO from Pseudomonas aeruginosa (PaBVMO); this has been exploited for the direct synthesis of medium‐chain α,ω‐dicarboxylic acids through a Baeyer–Villiger oxidation–hydrolysis cascade. PaBVMO displayed the highest abnormal regioselectivity toward a variety of long‐chain aliphatic keto acids (C₁₆–C₂₀) to date, affording dicarboxylic monoesters with a ratio of up to 95 %. Upon chemical hydrolysis, α,ω‐dicarboxylic acids and fatty alcohols are readily obtained without further treatment; this significantly reduces the synthetic steps of α,ω‐dicarboxylic acids from renewable oils and fats.     

Effective Baeyer–Villiger oxidation of ketones over germanosilicates

Germanosilicates with various topologies (UTL, BEC, UWY, IWR) serve as efficient heterogeneous catalysts for the Baeyer–Villiger oxidation of ketones. The tetrahedrally coordinated Ge ions in germanosilicates exhibited Lewis acidity, and acted as the active sites for converting ketones to corresponding lactones effectively.     

Combined biological and chemical oxidation of ferrous sulfate using immobilised Thiobacillus ferrooxidans

Thiobacillus ferrooxidans immobilised in biomass support particles with activated carbon coating were used in a packed‐bed bioreactor to study the combined effects of chemical and biological catalysis on the oxidation of ferrous iron. The effect of ferrous iron concentration (in the range 5–30 kg m⁻³) and of its volumetric loading on the kinetics of reaction were investigated. With low concentrations of ferrous iron, 5–10 kg m⁻³, the combined catalysis did not offer a significant advantage to oxidation of ferrous iron and the kinetics of reaction were slightly faster than those achieved with just the biological catalyst. With ferrous iron at a concentration of 20 kg m⁻³, the combination of chemical and biological catalysis resulted in a remarkable enhancement of the reaction rate. The maximum oxidation rate of ferrous iron in the presence of combined catalysts, 21.9 kg m⁻³ h⁻¹, was twice as high as that achieved with just the biological catalyst. © 1999 Society of Chemical Industry     

Highly active InOx/TUD-1 catalyst towards Baeyer–Villiger oxidation of cyclohexanone using molecular oxygen and benzaldehyde

InOx/TUD-1 is prepared by sol–gel method and characterized by different techniques. On the basis of different characterization results it is found that spongy porous InOx/TUD-1 (In/Si = 8/100) matrix contains small crystallite of indium oxide in + 3 oxidation state. InOx/TUD-1 (In/Si = 8/100) catalyst shows good catalytic results for Baeyer–Villiger oxidation of cyclic ketones using molecular oxygen and sacrificial reagent benzaldehyde. The cyclohexanone conversion was found 100% with ε-caprolactone selectivity 100% using polar aprotic solvents e.g. dichloroethane, acetonitrile and benzonitrile in the presence of molecular oxygen.     

Application of a thermostable Baeyer–Villiger monooxygenase for the synthesis of branched polyester precursors

BACKGROUND

It is widely accepted that the poor thermostability of Baeyer–Villiger monooxygenases limits their use as biocatalysts for applied biocatalysis in industrial applications. The goal of this study was to investigate the biocatalytic oxidation of 3,3,5‐trimethylcyclohexanone using a thermostable cyclohexanone monooxygenase from Thermocrispum municipale (TmCHMO) for the synthesis of branched ?‐caprolactone derivatives as building blocks for tuned polymeric backbones. In this multi‐enzymatic reaction, the thermostable cyclohexanone monooxygenase was fused to a phosphite dehydrogenase (PTDH) in order to ensure co‐factor regeneration.

RESULTS

Using reaction engineering, the reaction rate and product formation of the regio‐isomeric branched lactones were improved and the use of co‐solvents and the initial substrate load were investigated. Substrate inhibition and poor product solubility were overcome using continuous substrate feeding regimes, as well as a biphasic reaction system with toluene as water‐immiscible organic solvent. A maximum volumetric productivity, or space–time‐yield, of 1.20 g L^‐1 h^‐1 was achieved with continuous feeding of substrate using methanol as co‐solvent, while a maximum product concentration of 11.6 g L^‐1 was achieved with toluene acting as a second phase and substrate reservoir.

CONCLUSION

These improvements in key process metrics therefore demonstrate progress towards the up‐scaled Baeyer–Villiger monooxygenase‐biocatalyzed synthesis of the target building blocks for polymer application. © 2018 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

     

Exploring the Substrate Specificity and Enantioselectivity of a Baeyer–Villiger Monooxygenase from Dietzia sp. D5: Oxidation of Sulfides and Aldehydes

Baeyer–Villiger monooxygenases (BVMOs) are valuable enzymes for specific oxyfunctionalization chemistry. They catalyze the oxidation of ketones to esters, but are also capable of oxidizing other chemical functions, namely aldehydes and heteroatoms such as sulfur, nitrogen, selenium and boron. The oxidation specificity and enantioselectivity of a newly characterized BVMO (BVMO4) from a strain of Dietzia towards sulfide- and aldehyde substrates have been studied. BVMO4 could react with sulfides containing an aromatic group. The presence of a substituent on the aromatic group was tolerated when they were in the meta- and para position and the oxidations yielded predominantly the (R)-sulfoxides. Similarly, BVMO4 displayed a higher activity for aldehydes containing a phenyl group, but long aliphatic aldehydes, namely octanal and decanal, were also accepted as substrate by this enzyme. The major oxidation products of the aldehyde substrates were the respective carboxylic acids in contrast to formate ester that was obtained in most of the previous reports. The Baeyer–Villiger oxidation of the substrate 2-phenylpropionaldehyde was studied in further detail and the corresponding acid product was obtained with good regio- and enantioselectivity. This is a unique feature for BVMO4 and is of great interest for further exploration of an alternative biocatalytic process.     

The Catalytic Baeyer–Villiger Oxidation of Cyclohexanone to ε-Caprolactone over Stibium-containing Hydrotalcite

A series of hydrotalcite-like compounds were prepared under microwave irradiation, which were used to catalyze the Baeyer–Villiger oxidation of cyclohexanone to ε-caprolactone with hydrogen peroxide as oxidant. The results show that stibium-containing hydrotalcite (Sb-HTL) has good catalytic properties in the reaction. In the Baeyer–Villiger oxidation of cyclohexanone to ε-caprolactone with H₂O₂ catalyzed by Sb-HTL, the effects of reaction time, reaction temperature, amount of catalyst and H₂O₂/cyclohexanone molar ratio are also investigated in details. It is shown the cyclohexanone conversion and ε-caprolactone selectivity can reach 79.15 and 93.84%, respectively, under the optimum reaction conditions. Furthermore, Sb-HTL can be reused for six times without obvious loss of activity and selectivity. Therefore, Sb-HTL is reusable and would be a promising catalyst for the Baeyer–Villiger oxidation using green and cheap oxidants like hydrogen peroxide instead of peroxycarboxylic acids.     

Biosynthesis of Hygrocins,Antitumor Naphthoquinone Ansamycins Produced by Streptomyces sp. LZ35

Hygrocins are naphthoquinone ansamycins with significant antitumor activities. Here, we report the identification and characterization of the hygrocin biosynthetic gene cluster (hgc) in Streptomyces sp. LZ35. A biosynthetic pathway is proposed based on bioinformatics analysis of the hgc genes and intermediates accumulated in selected gene disruption mutants. One of the steps during the biosynthesis of hygrocins is a Baeyer–Villiger oxidation between C5 and C6, catalyzed by luciferase‐like monooxygenase homologue Hgc3. Hgc3 represents the founding member of a previously uncharacterized family of enzymes acting as Baeyer–Villiger monooxygenases.     

Molybdenum(VI) Amino Triphenolate Complexes as Catalysts for Sulfoxidation,Epoxidation and Haloperoxidation

Two molybdenum(VI) complexes bearing a C₃ symmetrical amino tris‐tert‐butylphenolate ligand have proved to be air‐ and water‐tolerant catalysts that efficiently catalyse, in high yields and selectivity, the oxidation of sulfides, olefins and halides. In particular high turnover frequencies and turnover numbers (TOF and TON) have been obtained for the cyclooctene epoxidation (catalyst loading down to 0.05%, TONs up to 88,000 and TOFs up to 7500 h⁻¹).     

Highly efficient and reusable Cu-MCM-41 catalyst for the Baeyer–Villiger oxidation of cyclohexanone

A series of Cu-MCM-41 with different Cu contents were successfully synthesized by the direct hydrothermal (DHT) method and evaluated in the Baeyer–Villiger oxidation of cyclohexanone, using only 2 molar equiv of benzaldehyde as sacrificial agents. High conversion (99.0%) of cyclohexanone and ε-caprolactone selectivity (100%) were detected over Cu-MCM-41 (23) within 3 h. Various physical–chemical characterizations, including BET, XRD, UV–vis and H₂-TPR, revealed that isolated Cu^2 + species in the MCM-41 framework were responsible for the catalytic activities. This catalyst could be reused for three times without discernible loss in its activity and selectivity.     

Chloromethyl polystyrene supported dendritic Sn complexes,preparation and catalytic Baeyer–Villiger oxidation

Dendritic Sn complexes were successfully incorporated to chloromethyl polystyrene through solid phase synthesis methodology and exhibited to be promising catalysts for the Baeyer–Villiger oxidation of ketones with hydrogen peroxide. Several cyclic and acyclic ketones were oxidized by hydrogen peroxide in a reaction catalyzed by these polymer-supported dendritic Sn complexes with high conversion and selectivity. The catalysts can be prepared in large scale in a simple manner without the utilization of any expensive materials and can be recycled as heterogeneous catalysts.     

MgO/SnO2/WO3 as catalysts for synthesis of ε-caprolactone over oxidation of cyclohexanone with peracetic acid

Different Mg/Sn/W mixed oxides prepared by precipitation were used as catalysts in the Baeyer–Villiger oxidation of cyclohexanone with a mixture of 50% hydrogen peroxide and acetic acid as oxidant. The Mg/Sn/W oxide obtained by precipitation from NH₃·H₂O was found to be the catalyst providing the highest yield of ε-caprolactone and initial catalytic activity among all samples.