The para-substituent effect and pH-dependence of the organometallic Baeyer-Villiger oxidation of rhenium-carbon bonds

We studied the Baeyer-Villiger (BV) type oxidation of phenylrhenium trioxide (PTO) by H(2)O(2) in the aqueous phase using Quantum Mechanics (density functional theory with the M06 functional) focusing on how the solution pH and the para-substituent affect the Gibbs free energy surfaces. For both PTO and MTO (methylrhenium trioxide) cases, we find that for pH > 1 the BV pathway having OH(-) as the leaving group is lower in energy than the one involving simultaneous protonation of hydroxide. We also find that during this organometallic BV oxidation, the migrating phenyl is a nucleophile so that substituting functional groups in the para-position of phenyl with increased electron-donating character lowers the migration barrier, just as in organic BV reactions. However, this substituent effect also pushes electron density to Re, impeding HOO(-) coordination and slowing down the reaction. This is in direct contrast to the organic analog, in which para-substitution has an insignificant influence on 1,2-addition of peracids. Due to the competition of the two opposing effects and the dependence of the resting state on pH and concentration, the reaction rate of the organometallic BV oxidation is surprisingly unaffected by para-substitution.     

Baeyer-villiger oxidation and oxidative cascade reactions with aqueous hydrogen peroxide catalyzed by lipophilic li[b(c(6) f(5) )(4) ] and ca[b(c(6) f(5) )(4) ](2)

Efficient and selective: Two lipophilic catalysts were used for Baeyer-Villiger (BV) oxidations to give lactones in high yields. Cascade reactions involving this BV oxidation were used to selectively obtain either unsaturated carboxylic acids or hydroxylactones in high yields from β-silyl cyclohexanones.     

过氧化脲在氧化反应中的应用研究进展

氧化反应是重要的有机合成单元反应,常采用H2O2或过氧酸等为氧化剂.近年来,过氧化脲作为一种清洁环保的固态H2O2,以其性质稳定、H2O2含量高(36.2%)且释放可控等优点,在众多氧化反应中得到了广泛应用.对过氧化脲在氧化反应中的应用进行了总结和概述,重点介绍了环氧化、Baeyer-Villiger氧化、N-氧化、硫醚氧化成砜和亚砜、氧化卤化等反应.     

Towards practical biocatalytic Baeyer-Villiger reactions: applying a thermostable enzyme in the gram-scale synthesis of optically-active lactones in a two-liquid-phase system

Baeyer-Villiger monooxygenases (BVMOs) are extremely promising catalysts useful for enantioselective oxidation reactions of ketones, but organic chemists have not used them widely due to several reasons. These include instability of the enzymes in the case of in vitro and even in vivo systems, reactant/product inhibition, problems with upscaling and the necessity of using specialized equipment. The present study shows that the thermally stable phenylacetone monooxygenase (PAMO) and recently engineered mutants can be used as a practical catalysts for enantioselective Baeyer-Villiger oxidations of several ketones on a preparative scale under in vitro conditions. For this purpose several parameters such as buffer composition, the nature of the solvent system and the co-factor regeneration system were optimized. Overall a fairly versatile and efficient catalytic system for enantioselective laboratory scale BV-oxidations of ketones was developed, which can easily be applied even by those organic chemists who are not well versed in the use of enzymes.     

Asymmetric glycolate aldol reactions using cinchonium phase-transfer catalysts

Cinchona phase-transfer catalysts (PTC) were developed for glycolate aldol reactions to give differentially protected 1,2-diol products. Silyl enol ether 9 reacted to generate benzhydryl-protected products. O-Allyl trifluorobenzyl cinchonium hydrofluoride CN-4 (20 mol %) catalyzed the addition of 9 to benzaldehyde to give 8 as a single syn-product in 76% yield and 80% ee. Recrystallization enriched the product to 95% ee, and a Baeyer-Villiger reaction transformed the product into useful ester intermediates. [reaction: see text]     

Real-time, on-line monitoring of organic chemical reactions using extractive electrospray ionization tandem mass spectrometry

Extractive electrospray ionization mass spectrometry (EESI-MS) for real-time monitoring of organic chemical reactions was demonstrated for a well-established pharmaceutical process reaction and a widely used acetylation reaction in the presence of a nucleophilic catalyst, 4-dimethylaminopyridine (4-DMAP). EESI-MS provides real-time information that allows us to determine the optimum time for terminating the reaction based on the relative intensities of the precursors and products. In addition, tandem mass spectrometric (MS/MS) analysis via EESI-MS permits on-line validation of proposed reaction intermediates. The simplicity and rapid response of EESI-MS make it a valuable technique for on-line characterization and full control of chemical and pharmaceutical reactions, resulting in maximized product yield and minimized environmental costs. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Enzymic Baeyer–Villiger Oxidations by Flavin-Dependent Monooxygenases

There has recently been a revival of interest in microbial biochemistry. Part of this resurgence is due to the increased presence of man-made organic compounds in the biosphere and the resultant interest in microorganisms which can degrade these xenobiotic molecules. Also, advances in genetic engineering have raised the possibility of utilizing the chemical machinery of bacteria for commercial profit and social benefit. The Baeyer-Villiger reaction is a useful transformation in organic synthesis which provides chemists with a gentle means of converting ketones into esters or lactones. The reaction, however, suffers from the problems of low yield and the need, in some cases, to utilize harsh conditions. There exist bacteria, capable of growth on aliphatic molecules, that contain enzymes which can catalyze Baeyer-Villiger reactions. These enzymes, known as monooxygenases, are involved in the breakdown of acyclic and alicyclic ketones to provide simpler carbon units for further catabolism. The gamut of reactions catalyzed by some of these enzymes is remarkable. This diversity, plus their availability in pure form in quantity by genetic engineering raises the possibility that these biocatalysts can be useful as reagents in organic synthesis.     

Stopped-flow electrospray ionization mass spectrometry: a new method for studying chemical reaction kinetics in solution

In this work a new mass spectrometry based method for monitoring the kinetics of chemical reactions in solution is described. A stopped-flow mixing instrument is coupled to an electrospray ionization (ESI) mass spectrometer via a novel type of interface. Chemical reactions are initiated by rapid mixing of two reactant solutions. The mixture is instantaneously transferred to a reaction tube where the kinetics can be monitored in real-time by ESI mass spectrometry. With the current setup, a time window from 2.5 to 36 seconds after mixing of the reactants can be monitored. The experimental setup is used to study the kinetics of acetylcholine hydrolysis under alkaline conditions as a function of pH. The intensities of reactant (acetylcholine) and product (choline) ions are monitored simultaneously as a function of time. The reaction is carried out under pseudo-first-order conditions and the intensity-time curves are well described by single exponentials. The rate constants determined from these fits compare favorably with previous data from the literature.     

The role of Acid catalysis in the baeyer-villiger reaction. A theoretical study

Quantum mechanical calculations at the B3LYP/6-311+G(d,p) level have examined the overall mechanism of the Baeyer-Villiger (BV) reaction with peroxyacetic acid. A series of reactions that include both the addition step and the subsequent alkyl group migration step included ketones, acetone, t-butyl methyl ketone, acetophenone, cyclohexyl methyl ketone, and cyclohexyl phenyl ketone. The combined data suggested that the first step for addition of the peroxyacetic acid oxidation catalyst to the ketone carbonyl to produce the Criegee or tetrahedral intermediate is rate-limiting and has activation barriers that range from 38 to 41 kcal/mol without the aid of a catalyst. The rate of addition is markedly reduced by the catalytic action of a COOH functionality acting as a donor-acceptor group affecting both its proton transfer to the ketone C═O oxygen in concert with transfer of the OOH proton to the carboxylic acid carbonyl. The second or alkyl group migration step has a much reduced activation barrier, and its rate is not markedly influenced by acid catalysis. The rate of both steps in the BV reaction is greatly influenced by the catalytic action of very strong acids.     

Discovery, application and protein engineering of Baeyer-Villiger monooxygenases for organic synthesis

Baeyer-Villiger monooxygenases (BVMOs) are useful enzymes for organic synthesis as they enable the direct and highly regio- and stereoselective oxidation of ketones to esters or lactones simply with molecular oxygen. This contribution covers novel concepts such as searching in protein sequence databases using distinct motifs to discover new Baeyer-Villiger monooxygenases as well as high-throughput assays to facilitate protein engineering in order to improve BVMOs with respect to substrate range, enantioselectivity, thermostability and other properties. Recent examples for the application of BVMOs in synthetic organic synthesis illustrate the broad potential of these biocatalysts. Furthermore, methods to facilitate the more efficient use of BVMOs in organic synthesis by applying e.g. improved cofactor regeneration, substrate feed and in situ product removal or immobilization are covered in this perspective.     

Hydrotalcites as catalysts for the Baeyer-Villiger oxidation of cyclic ketones with hydrogen peroxide/benzonitrile

Hydrotalcites (HTs) in variable Mg/Al ratios were used as catalysts for the Baeyer-Villiger (BV) oxidation of cyclic ketones with hydrogen peroxide. All HTs studied were found to be active in the BV oxidation of cyclohexanone, their activity increases with increasing Mg/Al ratio. The reaction, which was conducted under very mild conditions (viz. atmospheric pressure and a temperature of 70 °C), provided conversions above 70% with 100% selectivity only after 6 h. This outcome was found to require the presence of a nitrile in the reaction medium, so a mechanism involving adsorption of the nitrile and cyclohexanone onto the catalyst is proposed that is consistent with the experimental results. Based on the proposed mechanism, the presence of a surfactant should result in improved conversion and catalytic activity, as was indeed observed with sodium dodecylsulfate in the reaction medium. The best catalyst among those tested was used with other cyclic ketones and found to provide excellent conversion and selectivity results in most cases.     

Protein engineering of stereoselective baeyer-villiger monooxygenases

Baeyer-Villiger monooxygenases (BVMOs) have been used for decades as catalysts in stereoselective Baeyer-Villiger reactions, including oxidative kinetic resolution of racemic ketones and desymmetrization of prochiral substrates with high enantioselectivity. These complement catalytic BV processes based on chiral synthetic catalysts. However, as in any enzyme-catalyzed process, limitations exist due to the often observed narrow substrate scope and/or insufficient stereoselectivity. Recent protein engineering of BVMOs in the form of directed evolution and rational design have eliminated these traditional limitations, which is the subject of this Minireview. The main focus is on phenylacetone monooxygenase (PAMO); an unusually thermostable and robust BVMO, which has a very narrow substrate scope. Protein engineering of PAMO has provided a number of mutants that display relatively wide substrate scope, high stereoselectivity, and maintained thermostability.     

Fluorous reverse-phase silica gel-supported Lewis acids as recyclable catalysts in water

Fluorous reverse-phase silica gel (FRPSG)-supported Lewis acids which have fluorous ligands acted as effective catalysts of Baeyer-Villiger and Diels-Alder reactions in water. Direct esterification of carboxylic acid with alcohol in organic media was also catalyzed. The FRPSG-supported Lewis acids could be recycled by simple filtration after the reaction.     

Diastereoselective Weitz-Scheffer epoxidation of levoglucosenone for the synthesis of isolevoglucosenone and derivatives

High-yielding epoxidation conditions for the cellulose pyrolysis product (?)-levoglucosenone (LGO) and 3-aryl derivatives of LGO have been developed. The reaction of LGO with hydrogen peroxide/base is known to give a Baeyer-Villiger reaction, however, it was found that the reactions of LGO or derivatives with tert-butylhydroperoxide/base affords solely epoxides through the Weitz-Scheffer reaction. A critical parameter in the successful isolation of the epoxide from LGO was to avoid all contact with water or alcohols during the reaction and workup. The epoxide products were reacted under Wharton conditions affording allylic alcohols and subsequent oxidation led to isolevoglucosenone or 3-arylisolevoglucosenone derivatives. Previously unreported reactions on isolevoglucosenone were then investigated.     

The Enzymology of Organic Transformations: A Survey of Name Reactions in Biological Systems

Chemical reactions that are named in honor of their true, or at least perceived, discoverers are known as “name reactions”. This Review is a collection of biological representatives of named chemical reactions. Emphasis is placed on reaction types and catalytic mechanisms that showcase both the chemical diversity in natural product biosynthesis as well as the parallels with synthetic organic chemistry. An attempt has been made, whenever possible, to describe the enzymatic mechanisms of catalysis within the context of their synthetic counterparts and to discuss the mechanistic hypotheses for those reactions that are currently active areas of investigation. This Review has been categorized by reaction type, for example condensation, nucleophilic addition, reduction and oxidation, substitution, carboxylation, radical‐mediated, and rearrangements, which are subdivided by name reactions.     

Heterogeneous Baeyer-Villiger oxidation of ketones with H2O2/nitrile, using Mg/Al hydrotalcite as catalyst

We synthesized a magnesium-aluminium hydrotalcite and used it as a catalyst in the Baeyer-Villiger (BV) oxidation of cyclohexanone with a mixture of 30% aqueous hydrogen peroxide and benzonitrile as oxidant. The hydrotalcite proved an excellent catalyst for the process. The influence of experimental variables was examined in depth in order to bring the working conditions as close as possible to those usable on an industrial scale. We optimized the cyclohexanone/hydrogen peroxide/benzonitrile proportion and used various nitriles, solvents and amounts of catalyst, benzonitrile and methanol proving the most effective nitrile and solvent, respectively, for the intended purpose. The reaction was found to occur to an acceptable extent with other carbonyl compounds as substrates; by exception, α,β-unsaturated carbonyl compounds provided poor results by effect of their undergoing competitive epoxidation of their double bonds.     

Baeyer-Villiger单加氧酶在有机合成中的应用

综述了Baeyer-Villiger单加氧酶在有机合成中的应用.较之传统的化学反应, 氧化酶催化剂反应有较好的选择性、可控性和经济性. 环己酮加氧酶是一种还原型辅酶I (NADPH)依赖型氧化酶, 是最早被报道能够催化Baeyer-Villiger氧化的酶. 这些重要反应产生了合成化学家很感兴趣的扩环产物. 环己酮加氧酶也是有用的生物催化剂, 由于辅酶再生的问题已被工程菌克服了, 所以能像全细胞催化剂那样使用. 对酮包括杂环酮进行Baeyer-Villiger氧化和动态动力学拆分, 放大这种反应作为合成路线是很有前途的.     

A novel organic intercalation system with layered polymer crystals as the host compounds derived from 1,3-diene carboxylic acids

A new type of organic intercalation system using poly(muconic acid) and poly(sorbic acid) crystals as the host compounds is described. The layered polymer crystals as the host are derived from benzyl-, dodecyl-, or naphthylmethylammonium salts of (Z,Z)-muconic or (E,E)-sorbic acids by topochemical polymerization. The subsequent solid-state hydrolysis of the resulting ammonium polymer crystals provides the corresponding carboxylic acid polymer crystals. When alkylamines are reacted with poly(muconic acid) or poly(sorbic acid) crystals dispersed in methanol at room temperature for a few hours, the intercalation proceeds to give layered ammonium polymer crystals via solid-state reactions, in which the polymers maintain a layered structure throughout. The interplanar spacing value of the polymer crystals changes according to the size of the guest molecules; that is, it exactly depends on the carbon number of the alkylamines used for each reaction of poly(muconic acid) or poly(sorbic acid) crystals. The stacking structure of alkyl chains with a tilt in the intercalated alkylammonium layers exists irrespective of the chemical and crystal structures of the host polymers. The intercalation of higher alkylamines into poly(muconic acid) crystals proceeds fast and quantitatively, while the conversion is dependent on the reaction conditions such as the structure and amount of the amine and the reaction time during the intercalation with poly(sorbic acid) crystals, due to the difference in the repeating layered structures of these polymer crystals. Some functional amines are also used as the guest molecules for this organic intercalation system.     

Evaluation of direct analysis in real time mass spectrometry for onsite monitoring of batch slurry reactions

Batch slurry reactions are widely used in the industrial manufacturing of chemicals, pharmaceuticals, petrochemicals and polymers. However, onsite monitoring of batch slurry reactions is still not feasible in production plants due to the challenge in analyzing heterogeneous samples without complicated sample preparation procedures. In this study, direct analysis in real time mass spectrometry (DART-MS) has been evaluated for the onsite monitoring of a model batch slurry reaction. The results suggested that automation of the sampling process of DART-MS is important to achieve quantitative results. With a sampling technique of manual sample deposition on melting point capillaries followed by automatic sample introduction across the helium beam, relative standard deviation (RSD) of the protonated molecule signals from the reaction product of the model batch slurry reaction ranged from 6 to 30%. This RSD range is improved greatly over a sampling technique of manual sample deposition followed by manual sample introduction where the RSDs are up to 110%. Furthermore, with the semi-automated sampling approach, semi-quantitative analysis of slurry samples has been achieved. Better quantification is expected with a fully automated sampling approach.     

A consecutive double-Criegee rearrangement using TFPAA: stepwise conversion of homoadamantane to oxahomoadamantanes

Rearrangement of 4-methylhomoadamantan-4-ol (1) with trifluoroperacetic acid (TFPAA) in trifluoroacetic acid (TFAA) proceeds with the formation of 4-oxahomoadamantane 6 and its derivatives (4 and 5). 2-exo-Hydroxy-4-oxahomoadamantane (5) and 6 were identified as a result of consecutive O-insertion Criegee rearrangement processes. The absence of methyl trifluoroacetate and methyl trifluoroperacetate among the reaction products, as well as the presence of acetyltrifluoroacetyl peroxide, is consistent with a double rather that a triple oxygen insertion during the course of the Criegee reaction. A mechanism involving initial Criegee rearrangement followed by a Baeyer-Villiger reaction is also excluded by kinetic considerations. The parallel formation of 4-ethyl-3-oxahomoadamantan-2-one (4) was determined to be the result of 4-methylhomoadmantan-4-ol (3) dehydration, with subsequent epoxidation of 4-methylhomoadamant-4-ene (32) to 4,5-epoxy-4-methylhomoadamantane (33), acid-catalyzed isomerization of 33 to 3-methylhomoadamantan-2-one (34), and Baeyer-Villiger oxidation to 3-methyl-5-oxabishomoadamantan-6-one (35). This sequence of reactions was followed by the acid-catalyzed isomerization to the final product 4. The proposed mechanisms for these transformations are discussed on the basis of model experiments and supporting density functional theory (DFT) calculations.