- Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization
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In this study, we combined photo-organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo-organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light-driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α-chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two-phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo-organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale.
- Zhang, Wuyuan,Fueyo, Elena Fernandez,Hollmann, Frank,Martin, Laura Leemans,Pesic, Milja,Wardenga, Rainer,H?hne, Matthias,Schmidt, Sandy
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supporting information
p. 80 - 84
(2019/01/04)
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- CATALYTIC OXIDATION OF 3,5,5-TRIMETHYLCYCLOHEXA-3-ENE-1-ONE (?-ISOPHORONE) WITH HYDROGEN PEROXIDE TO AFFORD 2,6,6-TRIMETHYL-2-CYCLOHEXENE-1,4-DIONE (KETO-ISOPHORONE)
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The present invention provides a novel process for producing 2,6,6-trimethyl-2-cyclohexene-1,4-dione (keto-isophorone) by catalytic oxidation of 3,5,5-trimethylcyclohexa-3-ene-1-one (β-isophorone) with hydrogen peroxide as the oxidant. In particular, the novel process includes phase transfer reagent in a biphasic system including an organic phase and an aqueous phase wherein the biphasic system includes 1) a tungsten polyoxyometallate as catalyst and hydrogen peroxide, and/or 2) a mixture of a) a mineral acid, b) hydrogen peroxide, and c) a metal tungstate.
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Page/Page column 0059-0060; 0061-0063; 0064-0066; 0067-0068
(2018/06/15)
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- Stereoselective hydroxylation of isophorone by variants of the cytochromes P450 CYP102A1 and CYP101A1
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The stereoselective oxidation of hydrocarbons is an area of research where enzyme biocatalysis can make a substantial impact. The cyclic ketone isophorone was stereoselectively hydroxylated (≥95%) by wild-type CYP102A1 to form (R)-4-hydroxyisophorone, an important chiral synthon and flavour and fragrance compound. CYP102A1 variants were also selective for 4-hydroxyisophorone formation and the product formation rate increased over the wild-type enzyme by up to 285-fold, with the best mutants being R47L/Y51F/I401P and A74G/F87V/L188Q. The latter variant, which contained mutations in the distal substrate binding pocket, was marginally less selective. Combining perfluorodecanoic acid decoy molecules with the rate accelerating variant R47L/Y51F/I401P engendered further improvement with the purified enzymes. However when the decoy molecules were used with A74G/F87V/L188Q the amount of product generated by the enzyme was reduced. Addition of decoy molecules to whole-cell turnovers did not improve the productivity of these CYP102A1 systems. WT CYP101A1 formed significant levels of 7-hydroxyisophorone as a minor product alongside 4-hydroxyisophorone. However the F87W/Y96F/L244A/V247L CYP101A1 mutant was ≥98% selective for (R)-4-hydroxyisophorone. A comparison of the two enzyme systems using whole-cell oxidation reactions showed that the best CYP101A1 variant was able to generate more product. We also characterised that the further oxidation metabolite 4-ketoisophorone was produced and then subsequently reduced to levodione by an endogenous Escherichia coli ene reductase.
- Dezvarei, Shaghayegh,Lee, Joel H.Z.,Bell, Stephen G.
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- Kinetics Study on Oxidation of β-Isophorone Using Molecular Oxygen
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The oxidation kinetics of β-isophorone (β-IP) using molecular oxygen catalyzed by iron(III) acetylacetonate was investigated in a lab-scale agitator bubbling reactor. β-IP was found to give keto-isophorone (KIP) and 4-hydroxy-3,5,5-trimethyl-2-cyclohexen-1-one (HIP) along with little isomerization product α-isophorone (α-IP). The results show that the oxidation reaction took place in the pseudo-first-order fast reaction regime. The experiment was conducted under the mass transfer reaction regime as the mass transfer resistances could not be easily eliminated. The intrinsic kinetics was obtained through apparent kinetics. The activation energy of oxidation of β-IP to KIP is 70.5 ± 4.1 kJ mol-1, and the value of ln AKIP is 33.53 ± 1.22. Meanwhile, the activation energy of oxidation of β-IP to HIP is 86.4 ± 5.4 kJ mol-1 and the value of ln AHIP is 36.23 ± 1.52, which could provide theoretical basis for industrial design, amplification of reactor, and the optimization of reaction.
- Chen, Zhirong,Fang, Tingting,Yuan, Shenfeng,Yin, Hong
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p. 295 - 303
(2016/05/02)
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- Improving the Monooxygenase Activity and the Regio- and Stereoselectivity of Terpenoid Hydroxylation Using Ester Directing Groups
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The monooxygenase enzyme CYP101B1, from Novosphingobium aromaticivorans DSM12444, binds norisoprenoids more tightly than monoterpenoids and oxidized these substrates with high regioselectivity. Ionols bound less tightly to CYP101B1 than ionones, but the levels of product formation remained high and the selectivity of oxidation was similar to that observed for the parent norisoprenoid. The structurally related sesquiterpene lactone (+)-sclareolide (9) was stereoselectively hydroxylated by CYP101B1 to (S)-(+)-3-hydroxysclareolide (9a). The turnover of monoterpenoid derivatives showed low levels of product formation and selectivity despite promising binding data. CYP101B1 catalyzed the selective oxidation of (1R)-(-)-nopol (14) and cis-jasmone (15), generating >90% (1R)-(-)-5-hydroxynopol (14a) and 4-hydroxy-cis-jasmone (15a), respectively. To develop strategies for the efficient and selective oxidation of monoterpenoid-based substrates using CYP101B1, we investigated the binding and catalytic properties of terpenoid acetates. The ester functional group of these substrates mimicked the carbonyl moiety of norisoprenoids and anchored the monoterpenoid acetates in the active site of CYP101B1 with high affinity for the monoterpenoid acetates. The oxidation of these substrates by CYP101B1 occurred with product formation rates in excess of 1000 min-1 and total turnover numbers of greater than 5000 being observed in all but one instance. Critically, the oxidations were regioselective, with several being stereoselective. (-)-Myrtenyl acetate (20) was oxidized regioselectively (>95%) to yield cis-4-hydroxy-myrtenyl acetate (20a), which was further oxidized to 4-oxomyrtenyl acetate (20b) using a whole-cell system, providing a biocatalytic route to generate intermediates used in the production of cannabinoid derivatives. The ester carbonyl moiety could also be used as a directing group also to enhance the activity and control the selectivity of P450-catalyzed reactions; for example, the turnover of l-(-)-bornyl acetate (18) and isobornyl acetate (19) by CYP101B1 generated 9-hydroxybornyl acetate (18a) and 5-exo-hydroxyisobornyl acetate (19a), respectively, as the sole products.
- Hall, Emma A.,Sarkar, Md. Raihan,Lee, Joel H. Z.,Munday, Samuel D.,Bell, Stephen G.
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p. 6306 - 6317
(2016/09/09)
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- Two catalytic systems of l-proline/Cu(II) catalyzed allylic oxidation of olefins with tert-butyl hydroperoxide
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The nontoxic and water-soluble l-proline combined with two different forms of copper(ii): recoverable Cu-Al hydrotalcite-like compounds (Cu-Al HTLcs) and water-soluble CuCl2, as a heterogeneous catalytic system (l-proline/Cu-Al HTLcs) and two-phase catalytic system (l-proline/CuCl2) to catalyze allylic oxidation with tert-butyl hydroperoxide. The results showed that l-proline/Cu(ii) is highly active for oxidizing isophorone (IP) into ketoisophorone (KIP). Maximum catalytic effects were afforded respectively under the optimal reaction conditions, which obtained 77.9% IP conversion with 74.3% KIP selectivity catalyzed by l-proline/Cu-Al HTLcs and 73.5% conversion with 81.6% selectivity by l-proline/CuCl2. Recycling experiments of the two catalytic systems of l-proline/Cu(ii) showed they are stable and recyclable for at least six cycles with appreciable catalytic activity. And various hydrocarbons could be smoothly transformed into corresponding ketones with satisfactory conversion and selectivity by the two catalytic systems.
- Yu, Peng,Zhou, Yin,Yang, Yingwei,Tang, Ruiren
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p. 65403 - 65411
(2016/07/26)
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- Novel catalytic system: N-hydroxyphthalimide/hydrotalcite-like compounds catalysing allylic carbonylation of cyclic olefins
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N-hydroxyphthalimide (NHPI) combined with stable and recoverable transition metal-aluminium binary hydrotalcite-like compounds (M-Al HTLcs, M = Cu, Ni, Co) as an unprecedented catalytic system was demonstrated for the allylic carbonylation, as the model reaction, of cyclic olefins with tert-butyl hydroperoxide (TBHP), using isophorone (IP) to ketoisophorone (KIP). The results showed NHPI combined with Cu-Al HTLcs to be an efficient catalytic system and the influences of various reaction conditions of the catalytic reaction were optimised. A maximum IP conversion of 68.0 % with 81.8 % selectivity to KIP was afforded under the optimal reaction conditions. Experiments of repeatability and restorability showed Cu-Al HTLcs to be stable for at least five cycles without noticeable loss of catalytic activity. Expanding substrates could also be efficiently converted to the corresponding ketones under the optimised reaction conditions with appreciable yields. A plausible catalytic reaction mechanism was proposed.
- Zhou, Yin,Tang, Rui-Ren,Song, Dan
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p. 888 - 897
(2017/02/05)
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- Chitosan-based Schiff base-metal complexes (Mn, Cu, Co) as heterogeneous, new catalysts for the β-isophorone oxidation
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A new chitosan-based Schiff base was prepared and complexed with manganese, cobalt and copper. These Schiff base metal complexes were used as heterogeneous catalysts for the air oxidation of β-isophorone to ketoisophorone. The obtained complexes were characterized by means of FT-IR,1HNMR spectroscopy, elemental analysis, powder X-ray diffraction, field emission gun scanning electron microscopy, electron spin resonance spectroscopy, ICP-AES and solubility tests. Thermal properties were also investigated using thermal gravimetric analysis. Data obtained by thermal analysis revealed that these complexes showed good thermal stability. The conversion and selectivity of β-isophorone to ketoisophorone for each prepared catalyst was studied using a batch reactor and gas chromatography for product identification and quantification. The results were compared against the homogeneous bis-salicylaldehyde ethylenedi-imine-Mn catalyst. The use of methanol, acetone, methyl isobutyl ketone and n-hexane as solvent and its effect on conversion and selectivity was also investigated. Acetone was found to be a promising solvent for the β-isophorone oxidation. The role of triethyl amine and acetyl acetone in the oxidation reaction has also been investigated.
- Thatte,Rathnam,Pise
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p. 727 - 737
(2014/07/07)
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- Metal and solvent-free oxidation of α-isophorone to ketoisophorone by molecular oxygen
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The metal and solvent-free oxidation of α-isophorone to ketoisophorone (KIP) using N-hydroxy phthalimide (NHPI) as the catalyst under atmospheric oxygen was studied, eliminating the isomerization process of α-isophorone to β-isophorone. The effect of co-catalyst, temperature, time, amount of NHPI, and recycling on the oxidation was investigated. The oxidation of α-isophorone proceed well without any co-catalyst under 60 °C for 10 h, which was different with the traditional oxidation of α-isophorone at high temperature. Furthermore, NHPI can be easily separated and reused with a slight loss on its activity. This aerobic oxidation process by NHPI provides a good alternative way for the industrial synthesis of KIP.
- Wang, Congmin,Wang, Guoliang,Mao, Jianyong,Yao, Zhen,Li, Haoran
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experimental part
p. 758 - 762
(2010/07/06)
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- Combination of two catalytic sites in a novel nanocrystalline TiO 2-iron tetrasulfophthalocyanine material provides better catalytic properties
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Mesoporous titania nanocrystals containing iron tetrasulfophthalocyanine (FePcS) have been synthesised by a one-pot hydrolytic process from a modified Ti alkoxide; the novel hybrid catalyst was efficient in heterogeneous oxidation of 2,3,6-trimethylphenol and β-isophorone suggesting a cooperative effect between TiO2 and FePcS catalytic sites. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2005.
- Beyrhouty, Mirvat,Sorokin, Alexander B.,Daniele, Stephane,Hubert-Pfalzgraf, Liliane G.
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p. 1245 - 1248
(2007/10/03)
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- Oxidation-isomerization of an olefin to allylic alcohol using titania-silica and a base co-catalyst
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The allylic oxidation of olefins is essential in synthetic organic chemistry, affording valuable α,β-unsaturated alcohols and carbonyl compounds. Allylic oxidation maintains the olefinic functionality in the product, thereby allowing further useful transformations. The potential two-step, one-pot synthesis of α,β-unsaturated alcohols from olefins was illustrated on the example of 4-hydroxyisophorone using titania-silica aerogels and basic co-catalysts. Kinetic analysis of the complex reaction network revealed that titania-silica was efficient in the epoxidation of β-isophorone (3,5,5-trimethyl-3-cyclohexen-1-one) with tert-butylhydroperoxide at 353 K, whereas the acid/base-catalyzed in situ rearrangement to 4-hydroxy-isophorone (4-hydroxy-3,5,5-trimethyl-cyclohex-2-eonone) was slow. Addition of solid bases such as CaO, Na2CO3 and KF/CaF2 accelerated the rearrangement and achieved ≤ 77.5% selectivity at 83% conversion in 3 hr. Stronger bases K2CO3, BaO, Mg-Al-O-tBu, guanidine bases) inhibited the epoxidation reaction due to the deactivation of the isolated Ti sites and favored isomerization of β-isophorone to α-isophorone. Hydrophobization of titania-silica by covalently bound surface phenyl groups greatly suppressed oligomerization and isomerization of β-isophorone but did not improve selectivity to 4-hydroxyl-isophorone.
- Beck,Mallat,Baiker
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- Electrochemical Epoxidation of Electron-Poor Olefins Using Silver Bipyridine Based Redox Mediators
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Electrogenerated and regenerated silver(III)oxo bis(2,2'-bipyridine) and similar complexes can act as redox catalysts for the indirect electrochemical epoxidation of electron-deficient olefins in aqueous acetonitrile.Thus, isobutyl methacrylate is electrolyzed to form the epoxide with 87percent material yield and 21percent current yield.
- Kandzia, Christof,Steckhan, Eberhard
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p. 3695 - 3698
(2007/10/02)
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- Identification of New Constituents of Quince Fruit Flavor (Cydonia oblo ga Mill. = C. vulgaris Pers.)
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As a flavor of quince fruit, four new bicyclononanes, 2,2,6,7-tetramethylbicyclonona-4,7,9(1)-triene (1), (+)-2,2,6,7-tetramethylbicyclonona-4,9(1)-dien-8-one (2), (-)-2,2,6,7-tetramethylbicyclonona-4,9(1)-dien-8-ol (3), and (-)-2,2,6,7-tetramethylbicyclonona-4,9(1)-diene-7,8-diol (4), have been identified.Racemic compounds 1-4 have been synthesized from 4-oxoisophorone by direct and regioselective reduction to 4-hydroxy-2,6,6-trimethyl-2-cyclohexen-1-one followed by ketal Claisen rearrangement. 3,4-Didehydro-β-ionol (5) has also bee n found to be one of the constituents of quince fruit oil.
- Ishihara, Masakazu,Tsuneya, Tomoyuki,Shiota, Haruyasu,Shiga, Minoru
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p. 491 - 495
(2007/10/02)
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