- Steric vs. electronic effects in the Lactobacillus brevis ADH-catalyzed bioreduction of ketones
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Lactobacillus brevis ADH (LBADH) is an alcohol dehydrogenase that is commonly employed to reduce alkyl or aryl ketones usually bearing a methyl, an ethyl or a chloromethyl as a small ketone substituent to the corresponding (R)-alcohols. Herein we have tested a series of 24 acetophenone derivatives differing in their size and electronic properties for their reduction employing LBADH. After plotting the relative activity against the measured substrate volumes we observed that apart from the substrate size other effects must be responsible for the activity obtained. Compared to acetophenone (100% relative activity), other small substrates such as propiophenone, α,α, α-trifluoroacetophenone, α-hydroxyacetophenone, and benzoylacetonitrile had relative activities lower than 30%, while medium-sized ketones such as α-bromo-, α,α-dichloro-, and α,α-dibromoacetophenone presented relative activities between 70% and 550%. Moreover, the comparison between the enzymatic activity and the obtained final conversions using an excess or just 2.5 equiv. of the hydrogen donor 2-propanol, denoted again deviations between them. These data supported that these hydrogen transfer (HT) transformations are mainly thermodynamically controlled. For instance, bulky α-halogenated derivatives could be quantitatively reduced by LBADH even employing 2.5 equiv. of 2-propanol independently of their kinetic values. Finally, we found good correlations between the IR absorption band of the carbonyl groups and the degrees of conversion obtained in these HT processes, making this simple method a convenient tool to predict the success of these transformations. The Royal Society of Chemistry.
- Rodriguez, Cristina,Borzecka, Wioleta,Sattler, Johann H.,Kroutil, Wolfgang,Lavandera, Ivan,Gotor, Vicente
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p. 673 - 681
(2014/01/06)
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- Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
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Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α-dihalogenated ketones, obtaining optically pure β,β-dichloro- or β,β-dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH-A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α-substituted ketones, namely α-bromo- α-chloro- and α-chloro-α-fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)-enantiomer was obtained by using ADH-A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de). Bulking up: A series of β,β-dihalohydrins are obtained through alcohol dehydrogenase (ADH) catalyzed bioreduction of the synthesized α,α-dihalogenated ketones. Two racemic acetophenone derivatives are also subjected to this protocol to obtain stereoenriched alcohols through dynamic kinetic resolution (DKR).
- Kedziora, Kinga,Bisogno, Fabricio R.,Lavandera, Ivan,Gotor-Fernandez, Vicente,Montejo-Bernardo, Jose,Garcia-Granda, Santiago,Kroutil, Wolfgang,Gotor, Vicente
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p. 1066 - 1072
(2014/05/06)
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- Versatile iridicycle catalysts for highly efficient and chemoselective transfer hydrogenation of carbonyl compounds in water
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Cyclometalated iridium complexes are shown to be highly efficient and chemoselective catalysts for the transfer hydrogenation of a wide range of carbonyl groups with formic acid in water. Examples include α-substituted ketones (α-ether, α-halo, α-hydroxy, α-amino, α-nitrile or α-ester), α-keto esters, β-keto esters and α,β-unsaturated aldehydes. The reduction was carried out at substrate/catalyst ratios of up to 50000 at pH 4.5 and required no organic solvent. The protocol provides a practical, easy and efficient way for the synthesis of β-functionalised secondary alcohols, such as β-hydroxyethers, β-hydroxyamines and β-hydroxyhalo compounds, which are valuable intermediates in pharmaceutical, fine chemical, perfume and agrochemical synthesis. Water wonder: Iridicycle catalysts are versatile and allow the highly efficient and chemoselective transfer hydrogenation of a variety of carbonyl compounds, including problematic and challenging ones, with formate in neat water (see scheme).
- Talwar, Dinesh,Wu, Xiaofeng,Saidi, Ourida,Salguero, Noemí Poyatos,Xiao, Jianliang
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supporting information
p. 12835 - 12842
(2015/03/30)
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- Laccase/TEMPO-mediated system for the thermodynamically disfavored oxidation of 2,2-dihalo-1-phenylethanol derivatives
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An efficient methodology to oxidize β,β-dihalogenated secondary alcohols employing oxygen was achieved in a biphasic medium using the laccase from Trametes versicolor/TEMPO pair, providing the corresponding ketones in a clean fashion under very mild conditions. Moreover, a chemoenzymatic protocol has been applied successfully to deracemize 2,2-dichloro-1-phenylethanol combining this oxidation with an alcohol dehydrogenase-catalyzed bioreduction. the Partner Organisations 2014.
- Kedziora, Kinga,Diaz-Rodriguez, Alba,Lavandera, Ivan,Gotor-Fernandez, Vicente,Gotor, Vicente
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supporting information
p. 2448 - 2453
(2014/05/06)
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- Efficient partial hydrogenation of trichloromethyl to gem-dichloromethyl groups in platinum on carbon-catalyzed system
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While gem-dichloromethyl groups can be directly synthesized by the mono-dechlorination of the corresponding trichloromethyl groups, the suppression control of the over-reduction to form chloromethyl or methyl functionalities is quite difficult. We have established the efficient and widely applicable mono-dechlorination method of the trichloromethyl groups to form the corresponding gem-dichloromethyl groups using platinum on carbon in dimethylacetamide as a specific solvent at 25 °C under a hydrogen atmosphere. The mono-dechlorination of the α,α,α- trichloromethylcarbonyl groups smoothly proceeded by the use of platinum on carbon as a catalyst in a highly chemoselective manner, while the efficient mono-dechlorination of the alkyl- and aryl-trichloromethyl groups required the combined use of Bu3SnH.
- Sawama, Yoshinari,Imanishi, Takahiro,Nakatani, Ryosuke,Fujiwara, Yuta,Monguchi, Yasunari,Sajiki, Hironao
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supporting information
p. 4540 - 4546
(2014/06/10)
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- Trichloromethyl ketones: Asymmetric transfer hydrogenation and subsequent Jocic-type reactions with amines
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Amino-amides are important pharmaceutical building-blocks. The enantioselective reduction of trichloromethyl ketones using ruthenium transfer hydrogenation catalysts is reported. The products react in a range of Jocic-type reactions to give enantiomerically enriched amino-amides.
- Perryman, Michael S.,Harris, Matthew E.,Foster, Jade L.,Joshi, Anushka,Clarkson, Guy J.,Fox, David J.
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supporting information
p. 10022 - 10024
(2013/10/22)
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- Decarboxylative bromination of cinnamic acids by 2-iodoxybenzoic acid with tetrabutylammonium bromide
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The decarboxylative bromination of cinnamic acids using the hypervalent iodine reagent 2-iodoxybenzoic acid with tetrabutylammonium bromide is described, providing good to excellent yields of bromostyrenes. Bromostyrenes are useful coupling components in a wide range of transition metal-catalysed coupling reactions.
- Han, Jianlei,Wei, Yuping
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p. 247 - 248
(2012/09/22)
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- MPV reduction using AlIII-calix[4]arene Lewis acid catalysts: Molecular-level insight into effect of ketone binding
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Catalytic Meerwein-Ponndorf-Verley (MPV) reduction using Al III-calix[4]arene complexes is investigated as a model system that requires the bringing together of two different chemical species, ketone and alkoxide, within a six-membered transition state. Two-point versus one-point ketone binding is demonstrated to be the most salient feature that controls MPV catalysis rate. A 7.7-fold increase in rate is observed when comparing reactants consisting of a bidentate Cl-containing ketone and sterically and electronically similar but looser-binding ketones, which are substituted with H and F. The one-point and two-point nature of ketone binding for the various ketones investigated is independently assessed using a combination of structural data derived from single-crystal X-ray diffraction and DFT-based molecular modeling. Using MPV catalysis with inherently chiral calix[4]arenes, the effect of multiple point reactant binding on enantioselectivity is elucidated. A higher denticity of ketone binding appears to increase the sensitivity of the interplay between chiral active site structure and MPV reduction enantioselectivity.
- Nandi, Partha,Matvieiev, Yuriy I.,Boyko, Vyacheslav I.,Durkin, Kathleen A.,Kalchenko, Vitaly I.,Katz, Alexander
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experimental part
p. 42 - 49
(2011/12/13)
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- A fast and selective decarboxylative difunctionalization and cyclization for easy access to gem-dihalo alcohol, ether, ester and bromo-1,4-dioxane
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A general strategy for fast decarboxylative difunctionalization to gem-dihalohydrin, gem-dihaloether, gem-dibromoester and cyclized bromo-1,4-dioxane synthons with outstanding regio- and stereoselectivity is demonstrated. The Royal Society of Chemistry 20
- Khamarui, Saikat,Sarkar, Deblina,Pandit, Palash,Maiti, Dilip K.
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supporting information; experimental part
p. 12667 - 12669
(2012/01/03)
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- Reductive Addition of Polyhalomethanes and Their Related Compounds to Aldehydes and 1,2-Elimination of the Coupling Products in a Pb/Al Bimetal Redox System
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A Pb/Al bimetal system was used to carry out reductive addition of tetrachloromethane, tetrabromomethane, bromotrichloromethane, trichloroacetamide, and trichloroacetonitrile to aldehydes.Subsequent 1,2-elimination of the halogen atom and hydroxyl group from the coupling products was also performed with the Pb/Al bimetal system.The technology was successfully applied to stereocontrolled syntheses of ethyl trans- and cis-3-(2,2-dihaloethenyl)-2,2-dimethylcyclopropanecarboxylates.
- Tanaka, Hideo,Yamashita, Shiro,Yamanoue, Motoi,Torii, Sigeru
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p. 444 - 450
(2007/10/02)
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- On the Mechanism of Reduction by Reduced Nicotinamide Adenine Dinucleotide Dependent Alcohol Dehydrogenase. α-Halo Ketones as Mechanistic Probes
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α-Haloacetophenones have been used as mechanistic probes for the enzyme (HLADH) controlled reductions by NADH.The cofactor, NADH, itself reduced the α-haloacetophenones and yielded the product diagnostic of free radical reduction, acetophenone.In the presence of NADH/HLADH both the α-fluoro- and α-chloroacetophenones, although they were only slightly reactive with NADH, yielded the hydride reduction products, optically active 1-phenyl-2-haloethanol.The more reactive α-bromoacetophenone was reduced by a radical chain process, which did not involve the enzyme.Ahalo ketone of intermediate reactivity, α,α-dichloroacetophenone, was reduced by the enzyme to give the products of heterolytic reduction.The suitability of the α-haloacetophenones as diagnostic mechanistic probes for enzyme reactivity and of dihydropyridines as NADH/HLADH models is discussed.
- Tanner, Dennis D.,Stein, A. R.
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p. 1642 - 1646
(2007/10/02)
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- Fluoride Ion-Catalyzed Generation and Carbonyl Addition of α-Halo Carbanions Derived from α-Halo Organosilicon Compounds
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The title carbanion species are generated from the corresponding α-haloorganosilicon compounds by the action of a catalytic amount of tris(diethylamino)sulfonium difluorotrimethylsilicate and are found to undergo addition to aldehyde carbonyl efficiently at ambient temperature.The synthetic potential of the reaction is demonstrated by application to the synthesis of some insecticides.
- Fujita, Makoto,Obayashi, Michio,Hiyama, Tamejiro
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p. 4135 - 4146
(2007/10/02)
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- STEREOCONTROL IN RADICAL CYCLIZATION: STEREOSELECTIVE SYNTHESIS OF 2,4-CIS AND 2,4-TRANS TETRAHYDROFURAN DERIVATIVES VIA MONO- OR DICHLOROMETHYL RADICAL.
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A novel stereocontrol method for the preparation of 2,4-disubstituted tetrahydrofurans was presented. 2,4-Cis-disubstituted-3,3-dichlorotetrahydrofurans 2 were provided predominantly by the radical cyclization of allyl-2,2,2-trichloroethylethers 1 with tributyltin hydride.The effect of geometry of chlorine atom and olefin on products stereochemistry was also discussed.
- Watanabe, Yoshihiko,Endo, Takeshi
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p. 321 - 324
(2007/10/02)
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- Synthesis, Structure, and Catalytic Activity of μ-Alkylthio- and μ-Arylthio-μ-chloro-dicarbonylbis(tri-tert-butylphosphane)dirhodium Complexes
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Tetracarbonyldi-μ-chloro-dirhodium (1) reacts with tri-tert-butylphosphane and alkyl or aryl trimethylsilyl sulfides 4 to give complexes tBu3)2Cl(SR)> (5a-i).The complexes 5h,i with the surface active trialkoxysilyl groups are fixed onto a fused silica support.The X-ray structural analyses of tBu3)2Cl(StBu)> (5c) and tBu3)2Cl(SC6H4Cl)> (5g) indicate a cis-configuration of the tri-tert-butylphosphane ligands.The new complexes catalyze the isomerization of 1-octen-3-ol (10) into 3-octanone (11), of 4-allylanisole (12) into cis- and trans-4-(1-propenyl)anisole (13), of trans-stilbene oxide (14) into desoxybenzoin (15), the transfer hydrogenation of α,β-unsaturated ketones by formic acid (16 -> 17), and the transfer hydrogenolysis of trihalomethyl compounds (18, 20) by halogen free alcohols.
- Schumann, Herbert,Cielusek, Guy,Jurgis, Stanislaw,Hahn, Ekkehardt,Pickardt, Joachim,et al.
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p. 2825 - 2838
(2007/10/02)
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- Oxyanionic Substituent Effect on the C-H Insertion of Carbenes. Reaction of Alkoxides with Dichlorocarbene and Chlorophenylcarbene
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The lithium alkoxides of benzylic, allylic, and simple alkyl alcohols were allowed to react with chloroform in the presence of t-BuOLi in THF-hexane to give, in 32-91percent yields, dichloromethylcarbinols, which were produced by the insertion of dichlorocarbene into the α C-H bond of alkoxides but not by the Wittig rearrangement of carbanions of alkyl dichloromethyl ethers.The enhanced reactivity toward dichlorocarbene of the α C-H bond of alkoxides was clearly demonstrated by the high selectivity of the insertion.The potassium alkoxides of a series of analogous alcohols reacted analogously with benzal chloride in the presence of t-BuOK in THF to give the corresponding substituted oxiranes (16-79percent); e.g., the reaction of potassium benzyl oxide gave 2,3-diphenyloxirane (79percent) as a mixture of stereoisomers (trans:cis = 1.0).With 2-phenethoxide, n-octyl oxide, or 2-methoxyethoxide, the corresponding dialkyl acetals of benzaldehyde were also formed in 9, 6, and 6percent yield, respectively, and their formation is explained in terms of nucleophilic attack of alkoxide on chlorophenylcarbene.With trans-crotyl oxide or 2-phenetoxide, 1,3-diphenylpropan-1-one(33percent) and 1-phenylpent-3-en-1-one (6percent) were produced, respectively, as byproducts through the isomerization of the primary product oxiranes.Oxiranes were produced by the insertion of chlorophenylcarbene into the α C-H bond of alkoxides followed by the cyclization of the intermediate 1-substituted 2-chloro-2-phenethyl alkoxide.These reactions provide us with new preparative methods of synthetically useful dichloromethyl carbinols and oxiranes.
- Harada, Toshiro,Akiba, Eiji,Oku, Akira
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p. 2771 - 2776
(2007/10/02)
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- NOVEL SYNTHESIS OF CARBOHYDRATES USING ELECTROREDUCTION AS KEY REACTIONS
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Glyceraldehyde was transformed to threose, erythrose, and erythrulose using electroreduction as key reactions.
- Shono, Tatsuya,Ohmizu, Hiroshi,Kise, Naoki
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p. 4801 - 4804
(2007/10/02)
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- Molecular Rearrangements. 13. Kinetics and Mechanism of Rearrangements of Some Ring-Substituted α-Chlorostyrene Oxides and trans-β-Chlorostyrene Oxides.
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The synthesis of certain phenyl-substituted derivatives of the isomeric trans-β-chlorostyrene oxides (6) and α-chlorostyrene oxides (7) are reported.The kinetics of rearrangement of 6 (X = p-CH3, H, p-Br, m-Cl, p-NO2) to phenylchloroacetaldehydes (12) in CCl4 buffered by Na2HPO4 and 7 (X = p-CH3, H, p-NO2) to ω-chloroacetophenones in CCl4 were determined by following the rates of disappearance of the α-chloro epoxide and formation of the α-chloro carbonyl product.These substituent effects at 130 deg C were correlated with ?+ constants, yielding ρ values of-3.5 and -0.57 for the rearrangements of 6 and 7, respectively.In nitrobenzene solvent, the kC6H5NO2/kCCl4 for 6 was 180 and for 7 was 1740, the latter solvent effect attributed to nucleophilic solvent participation.It was concluded that these thermal rearrangements of 6 and 7 occur by disrotatory Cβ-O bond heterolysis to yield the corresponding α-keto carbonium-chloride ion pairs.
- McDonald, Richard N.,Cousins, Raymond C.
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p. 2976 - 2984
(2007/10/02)
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