Baeyer-Villiger Oxidation Reaction Research Articles

ChemInform Abstract: A Simple Route for the Synthesis of Novel 1,4‐Benzoxazine Derivatives by Baeyer—Villiger Oxidation Reaction.

Abstract Novel 1,4-benzoxazine derivatives were synthesized by an efficient and simple method in high yields. Readily available starting materials, operational simplicity, mild reaction conditions and novelty are the key advantages of this method. The synthetically attractive feature of the procedure is reflected by its applicability to a wide range of isatin and aniline derivatives. Besides their novel structures, these compounds may have important biological activities and industrial applications. Furthermore, we demonstrated that in Baeyer–Villiger oxidation reaction, the phenyl group migrate better than amidine groups but not as good as amide group. The migratory ability for these groups in Baeyer–Villiger oxidation reaction is ranked amide > phenyl > amidine.

A simple route for the synthesis of novel 1,4-benzoxazine derivatives by Baeyer–Villiger oxidation reaction

Novel 1,4-benzoxazine derivatives were synthesized by an efficient and simple method in high yields. Readily available starting materials, operational simplicity, mild reaction conditions and novelty are the key advantages of this method. The synthetically attractive feature of the procedure is reflected by its applicability to a wide range of isatin and aniline derivatives. Besides their novel structures, these compounds may have important biological activities and industrial applications. Furthermore, we demonstrated that in Baeyer–Villiger oxidation reaction, the phenyl group migrate better than amidine groups but not as good as amide group. The migratory ability for these groups in Baeyer–Villiger oxidation reaction is ranked amide > phenyl > amidine.

ChemInform Abstract: Palladium‐Catalyzed Suzuki—Miyaura, Heck and Hydroarylation Reactions on (‐)‐Levoglucosenone and Application to the Synthesis of Chiral γ‐Butyrolactones.

AbstractChiral 3‐ and 4‐substituted γ‐butyrolactones are obtained involving a Baeyer—Villiger oxidation reaction.

Fe–Co/sulfonated polystyrene as an efficient and selective catalyst in heterogeneous Baeyer–Villiger oxidation reaction of cyclic ketones

A highly efficient catalyst Fe–Co/sulfonated polystyrene (Fe–Co/SPS) was introduced and synthesized, which catalyzed BV oxidation of ketones with aqueous hydrogen peroxide to give the corresponding lactones in high yield and selectivity. Solid acid catalyst of Fe–Co/SPS has been prepared by using the 98-wt% sulfuric acid as the sulfonating agent and CoCl2 combined FeCl3 as sources of metal ions. Various physical–chemical characterizations including FT-IR, XRD, SEM and TGA, revealed that bimetallic ions Fe3+–Co2+ species in the sulfonated polystyrene framework were responsible for the catalytic activities. The BV reaction catalyzed by Fe–Co/SPS highlighted the special effects between metal ions and protonic acids as well as solvent-free heterogeneous catalytic oxidation with excellent conversion.

Fabrication of Fe3O4‐l‐dopa‐CuII/SnIV@Micro‐Mesoporous‐SiO2 Catalyst Applied to Baeyer–Villiger Oxidation Reaction

AbstractA Magnetic mFe3O4‐l‐dopa‐CuII/SnIV@micro‐mesoporous‐SiO2 catalyst was successfully prepared. The catalyst exhibits high and stable catalytic activity for the Baeyer–Villiger oxidation reaction with air as oxidant. Furthermore, the selectivity can reach nearly 100 %. Meanwhile the catalyst can be easily separated by an external magnet and reused at least up to five cycles without any notable loss in catalytic activity. In addition, the effect of Sn and Cu on the oxidation of cyclohexanone is discussed.

Photocycloaddition and Rearrangement Reactions in a Putative Route to the Skeleton of Plicamine-Type Alkaloids

Two isoquinolones were prepared, to which an allenyl side chain was linked at position C4 via a stereogenic silyloxy-substituted carbon atom. Intramolecular [2+2] photocycloaddition reactions of these substrates proceeded with high diastereoselectivity and delivered the respective cyclobutanes with an exocyclic methylene group (83% and 49% yield). With the 5,6-dioxoloisoquinolone precursor an unprecedented meta-photocycloaddition was observed as a significant side reaction, which occurred at positions C4 and C8a of the isoquinolone skeleton. The cyclobutane products were, after N-alkylation and transformation into the respective cyclobutanones (22–57%), subjected to various rearrangement reactions. In detail, a direct photochemical rearrangement, thermal and photochemical Beckmann rearrangements, and Baeyer–Villiger oxidation reactions were studied. In all cases, products were found, which resulted from cleavage of the amino-substituted cyclobutane bond, but not from the desired cleavage of the alternative alkyl-substituted cyclobutane bond.

Theoretical Studies on the Asymmetric Baeyer-Villiger Oxidation Reaction of 4-Phenylcyclohexanone with m-Chloroperoxobenzoic Acid Catalyzed by Chiral Scandium(III)-N,N'-Dioxide Complexes.

The mechanism and enantioselectivity of the asymmetric Baeyer-Villiger oxidation reaction between 4-phenylcyclohexanone and m-chloroperoxobenzoic acid (m-CPBA) catalyzed by Sc(III) -N,N'-dioxide complexes were investigated theoretically. The calculations indicated that the first step, corresponding to the addition of m-CPBA to the carbonyl group of 4-phenylcyclohexanone, is the rate-determining step (RDS) for all the pathways studied. The activation barrier of the RDS for the uncatalyzed reaction was predicted to be 189.8 kJ mol(-1) . The combination of an Sc(III) -N,N'-dioxide complex and the m-CBA molecule can construct a bifunctional catalyst in which the Lewis acidic Sc(III) center activates the carbonyl group of 4-phenylcyclohexanone while m-CBA transfers a proton, which lowers the activation barrier of the addition step (RDS) to 86.7 kJ mol(-1) . The repulsion between the m-chlorophenyl group of m-CPBA and the 2,4,6-iPr3 C6 H2 group of the N,N'-dioxide ligand, as well as the steric hindrance between the phenyl group of 4-phenylcyclohexanone and the amino acid skeleton of the N,N'-dioxide ligand, play important roles in the control of the enantioselectivity.

Lactone-bound structures of cyclohexanone monooxygenase provide insight into the stereochemistry of catalysis.

The Baeyer-Villiger monooxygenases (BVMOs) are microbial enzymes that catalyze the synthetically useful Baeyer-Villiger oxidation reaction. The available BVMO crystal structures all lack a substrate or product bound in a position that would determine the substrate specificity and stereospecificity of the enzyme. Here, we report two crystal structures of cyclohexanone monooxygenase (CHMO) with its product, ε-caprolactone, bound: the CHMO(Tight) and CHMO(Loose) structures. The CHMO(Tight) structure represents the enzyme state in which substrate acceptance and stereospecificity is determined, providing a foundation for engineering BVMOs with altered substrate spectra and/or stereospecificity. The CHMO(Loose) structure is the first structure where the product is solvent accessible. This structure represents the enzyme state upon binding and release of the substrate and product. In addition, the role of the invariant Arg329 in chaperoning the substrate/product during the catalytic cycle is highlighted. Overall, these data provide a structural framework for the engineering of BVMOs with altered substrate spectra and/or stereospecificity.

The Structural Basis for BVMO Substrate Profile and Stereospecificity

The Baeyer-Villiger monooxygenases (BVMOs) are a group of bacterial enzymes that are able to catalyze the synthetically useful Baeyer-Villiger oxidation reaction. As such, these enzymes have attracted considerable attention as potential industrial biocatalysts. The interest in these enzymes has led to a desire to be able to rationally design them for tailored biocatalytic applications. While recent years have seen the publication of a number of crystal structures (1-3), we have been lacking a structure of a BVMO that has its native substrate or product bound in a conformation that will allow the determination of substrate specificity and stereospecificity. Without such a structure, progress towards tailored BVMOs has been hampered. We have been able to solve two crystal structures of cyclohexanone monooxygenase (CHMO) with its lactone product, ε-caprolactone, bound. These structures place the lactone in an ideal position for the determination of its substrate specificity and stereospecificity. These structures have provided us with a better understanding of the structural basis for substrate binding, paving the way for the rational design of tailored BVMOs. At the same time, we have pursued small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) studies to better understand the dynamic nature of the enzyme. These studies have allowed us to explain the relationship between the various crystallized states of BVMOs and their complex, fourteen step enzyme mechanism.

Study of the catalytic activity of Al-Fe pillared clays in the Baeyer–Villiger oxidation

AbstractThree types of AlFePILCs pillared clays have been prepared from Algerian clay precursors. They have been characterized and tested in the Baeyer–Villiger oxidation of cyclohexanone to caprolactone using benzaldehyde and oxygen as oxidant at room temperature. The structural and textural properties of the catalyst have been determined by X-ray diffraction, nitrogen adsorption-desorption isotherms and Mössbauer spectroscopy.The different activities of the clays have been related to their Fe contents and accessible surface areas. The induction period observed before the reaction started has been attributed to the dissolution of a portion of the Fe3+ cations, mediated by either the perbenzoic acid intermediate or the benzoic acid co-product. The reaction was indeed catalysed by a few ppm of dissolved iron cations and the catalysis of the Baeyer–Villiger oxidation reaction should mechanistically be considered as homogeneous.

The Substrate-Bound Crystal Structure of a Baeyer–Villiger Monooxygenase Exhibits a Criegee-like Conformation

The Baeyer–Villiger monooxygenases (BVMOs) are a family of bacterial flavoproteins that catalyze the synthetically useful Baeyer–Villiger oxidation reaction. This involves the conversion of ketones into esters or cyclic ketones into lactones by introducing an oxygen atom adjacent to the carbonyl group. The BVMOs offer exquisite regio- and enantiospecificity while acting on a wide range of substrates. They use only NADPH and oxygen as cosubstrates, and produce only NADP+ and water as byproducts, making them environmentally attractive for industrial purposes. Here, we report the first crystal structure of a BVMO, cyclohexanone monooxygenase (CHMO) from Rhodococcus sp. HI-31 in complex with its substrate, cyclohexanone, as well as NADP+ and FAD, to 2.4 Å resolution. This structure shows a drastic rotation of the NADP+ cofactor in comparison to previously reported NADP+-bound structures, as the nicotinamide moiety is no longer positioned above the flavin ring. Instead, the substrate, cyclohexanone, is found at this location, in an appropriate position for the formation of the Criegee intermediate. The rotation of NADP+ permits the substrate to gain access to the reactive flavin peroxyanion intermediate while preventing it from diffusing out of the active site. The structure thus reveals the conformation of the enzyme during the key catalytic step. CHMO is proposed to undergo a series of conformational changes to gradually move the substrate from the solvent, via binding in a solvent excluded pocket that dictates the enzyme’s chemospecificity, to a location above the flavin–peroxide adduct where catalysis occurs.

Theoretical study on the hypervalent λ3-bromane strategy for Baeyer–Villiger oxidation of benzaldehyde and acetaldehyde: rearrangement mechanism

The rearrangement mechanisms of the novel Baeyer-Villiger oxidation (BVO) of benzaldehyde and acetaldehyde have been studied using density functional theory methods. All structures associated with the product formation step of the new Criegee intermediate, α-hydroxyalkoxy-λ(3)-bromane, are reported. B3LYP/6-31++G** calculations give a good description for the group shift of these two typical reactants: phenyl shift is easier than hydrogen shift for benzaldehyde; hydrogen migration is more favorable than methyl migration for acetaldehyde. Different mechanisms and various conformers of the novel BVO reaction have been considered for the migration step. Solvent effects and rate constants are also taken into account. The calculated and experimentally observed branching ratios are in good agreement with each other.

New mesoporous magnesium–aluminum mixed oxide and its catalytic activity in liquid phase Baeyer–Villiger oxidation reaction

Baeyer–Villiger oxidation is a very important reaction in the organic synthesis for designing value added lactone/esters from the respective carbonyl compounds. Usually an active metal-containing material in the presence of peroxides catalyzes this reaction. Here mesoporous magnesium–aluminum mixed oxide material has been synthesized hydrothermally using lauric acid as structure-directing or capping agent. This mesoporous material is thoroughly characterized by powder XRD, N2 and CO2 adsorption, HR TEM, FE SEM-EDS, FT IR and TG-DTA techniques. The material showed moderately good surface area (244m2g−1) and mesoporosity with nanoscale pore dimension (ca. 4.8nm). Liquid phase Baeyer–Villiger oxidations of cyclic and acyclic ketones have been carried out using this mesoporous material as catalyst in the presence of hydrogen peroxide as oxidant and benzonitrile as promoter.

Synthesis and catalytic properties of mesoporous alumina supported aluminium chloride with controllable morphology, structure and component

Aluminium chloride supported by tubular alumina, which was treated by absorbent cotton as a template, was prepared via chemical tailoring method. Scanning electron microscopy, transmission electron microscopy, N2 adsorption techniques and X-ray diffraction characterization showed alumina well replicated the nanoporous morphologies and hierarchical pore size of original cotton, and via chemical tailoring method, the active component aluminium chloride distributed evenly on the surface of the support. Using different concentration of hydrochloric acid, the morphology, structure and component of tubular alumina supported aluminium chloride could be controllably synthesized. The Baeyer–Villiger oxidation reactions of ketones catalyzed by the supported aluminium chloride, with 30% hydrogen peroxide as an oxidant, were carried out. The experimental results revealed that this type of reactions could proceed in ethanol at 70 °C with good yield (96%) and high regioselectivity (99%), exemplified by transforming of 2-adamantanone. The tubular alumina supported aluminium chloride could be reused several times without significant losses of their catalytic activity and selectivity.

Enzymatic Promiscuity for Organic Synthesis and Cascade Process

Enzymatic promiscuity, namely the possibility that one active site of an enzyme can catalyze several different chemical transformations, has been an important research field and valuable synthesis tool for protein engineering and synthetic chemistry. This review will focus on promiscuous enzyme-mediated reactions that are useful in organic synthesis. Examples include promiscuous hydrolysis reactions, Michael addition, Markovnikov addition, aldol condensation, Henry reaction, Mannich reaction, Epoxidation reaction, Baeyer-Villiger oxidation, radical polymerization and tandem reactions catalyzed by natural enzymes or engineered enzymes with existing or induced catalytic promiscuity. Among these examples, many enzymes from different family have been verified to be able to catalyze the same type of reaction through distinct mechanism. Many complex compounds or important intermediates can be synthesized using promiscuous enzymes or through novel synthesis pathways. These examples support the enormous potential of enzymatic promiscuity in synthetic chemistry. Keywords: Enzymatic promiscuity, Organic synthesis, Application, Michael addition, Oxidation, promiscuity, synthesis, catalytic promiscuity, substrate promiscuity, condition promiscuity, Hydrolysis, hydrolases, AP, acrylamide, solvents, chemoselectivity, (DA), (AA), DMSO, Triazole, CAL-B mutant, C-C Bond, CAL-B, lipase-MY, 1ipasePL, enantioselectivity, D-aminoacylase, (MJML), DMF, Aldol reaction, (DDG), heterocyclic aldehydes, MPS, kcat/Km, AMDase, (PLP), HbHNL, (MML), Haloperoxidases, H2O2, PFE, Pseudomonas sp, (UHP), (TMPME), Baeyer-Villiger Oxidation, Metalloenzymes, CA[Mn], (BARS1), Grob fragmentation, Mhpc, (CDNB), Lipase

Total synthesis of the marine polypropionates, siphonarienal, siphonarienone, and pectinatone

The synthesis of the marine natural products, siphonarienal, siphonarienone, and pectinatone is described employing desymmetrization strategy to create three consecutive stereogenic centers. The key intermediate 7 was made by asymmetric hydroboration of the known meso-olefin using (−)-IPC 2BH followed by PCC and Baeyer-Villiger oxidation reactions.

Study of Friedel-Crafts acylation and Baeyer-Villiger oxidation reactions on benzocycloheptanones and 1-tetralones in acid media

Synthesis and characterization of some new substituted naphthopyrones (2a-d) and 4,5-dihydro-3H-benzo[b]oxocin/oxepin-2-ones (3a-d), starting from 1-tetralone and benzocycloheptanones have been reported. Biological testing of these compounds for their antimicrobial activity has been carried out.

Synthesis, characterization and degradability of the novel aliphatic polyester bearing pendant N-isopropylamide functional groups

The synthesis, characterization, and degradability of the novel aliphatic polyester bearing pendant N-isopropylamide functional group are reported for the first time. 2-( N-Isopropyl-2-carbamoylethyl)cyclohexanone (CCH) was first synthesized by the Michael reaction of N-isopropylacrylamide with cyclohexanone and was subsequently converted into 6-( N-isopropyl-2-carbamoylethyl)-ɛ-caprolactone (CCL) by the Baeyer-Villiger oxidation reaction using 3-chloroperoxybenzoic acid ( mCPBA) as the oxidant. Finally, the novel functionalized poly(ɛ-caprolactone) bearing the pendant N-isopropylamide functional groups, poly(6-( N-isopropyl-2-carbamoylethyl)-ɛ-caprolactone- co-ɛ-caprolactone)s (poly(CCL- co-CL)), were carried out successfully by bulk ring-opening polymerization of CCL and ɛ-CL initiated by Sn(Oct) 2. Poly(CCL- co-CL) were characterized by 1H NMR, 13C NMR, SEC and DSC. The copolymer containing 9.1 mol% CCL formed flexible films and was used to study its degradability. A phosphate buffer (pH = 7.4) with temperature 37 °C was adopted to proceed the degrading study all through. Compared with poly(ɛ-caprolactone), the hydrolytic degradation of poly(CCL- co-CL) was much faster, which is confirmed by the weight loss and change of intrinsic viscosity.

The Role of Hydrogen Bonds in Baeyer−Villiger Reactions

Various Baeyer-Villiger (B-V) oxidation reactions were examined by density functional theory calculations. Proton movements in transition states (TSs) of the two key steps, the nucleophilic addition of a peroxyacid molecule to a ketone (TS1) and the migration-cleavage of O-O (TS3), were discussed. A new TS of a hydrogen-bond rearrangement in the Criegee intermediate (TS2) was found. The hydrogen-bond directionality requires a trimer of the peroxyacid molecules at the nucleophilic addition of a peroxyacid molecule to a ketone TS (TS1). At the migration-cleavage of O-O TS (TS3), also three peroxyacid molecules are needed. Elementary processes of the B-V reaction were determined by the use of the (acetone and (H-CO-OOH)n, n=3) system. The geometries of the nucleophilic addition of a peroxyacid molecule to a ketone TS (TS1) and the migration-cleavage of O-O TS (TS3) in the trimer (n=3) participating are nearly insensitive to the substituent on the peroxyacid. The directionality is satisfied in those geometries. The migration-cleavage of O-O TS (TS3) was found to be rate-determining in reactions, [Me2C=O+(H-CO-OOH)3], [Me2C=O+(F3C-CO-OOH)3], and [Me2C=O+(MCPBA)3]. In contrast, the nucleophilic addition of a peroxyacid molecule to a ketone (TS1) is rate-determining in the reaction, [Ph(Me)C=O+(H-CO-OOH)3].

The Last Reaction Producing Brassinolide Is Catalyzed by Cytochrome P-450s, CYP85A3 in Tomato and CYP85A2 in Arabidopsis

Brassinosteroids are steroidal hormones essential for the growth and development of plants. Brassinolide, the most biologically active brassinosteroid, has a seven-membered lactone ring that is formed by a Baeyer-Villiger oxidation of its immediate precursor castasterone. Despite its potential key role in controlling plant development, brassinolide synthase has not been identified. Previous work has shown that the formation of castasterone from 6-deoxocastasterone is catalyzed by members of the CYP85A family of cytochrome P-450 monooxygenases. A null mutation in the tomato Dwarf (CYP85A1) gene, extreme dwarf (d(x)), causes severe dwarfism due to brassinosteroid deficiency, but the d(x) mutant still produces fruits. Here, we show that d(x) fruits contain brassinolide at a higher level than wild-type fruits and that a new CYP85A gene, CYP85A3, is preferentially expressed in tomato fruits. Tomato CYP85A3 catalyzed the Baeyer-Villiger oxidation to produce brassinolide from castasterone in yeast, in addition to the conversion of 6-deoxocastasterone to castasterone. We also show that Arabidopsis CYP85A2, which was initially characterized as castasterone synthase, also has brassinolide synthase activity. Exogenous application of castasterone and brassinolide to the Arabidopsis cyp85a1/cyp85a2 double mutant suggests that castasterone can function as an active brassinosteroid but that its conversion into brassinolide is necessary for normal vegetative development in Arabidopsis. We postulate that castasterone is the major active brassinosteroid during vegetative growth in tomato, whereas brassinolide may play an organ-specific role in fruit development in this species.