- New continuous production process for enantiopure (2R,5R)-hexanediol
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A new continuous production process has been developed for optically active pure (2R,5R)-hexanediol. The process uses resting whole cells of Lactobacillus kefir DSM 20587 as a biocatalyst. The reduction of (2,5)-hexanedione to (2R,5R)-hexanediol was carried out in a 2-L continuously operated membrane reactor. Conversion of (2,5)-hexanedione was nearly quantitative and the selectivity between product and intermediate was 78% for the product. Enantioselectivity and diastereoselectivity were >99% for the whole period. The productivity of L. kefir could be increased by factor 30. (2R,5R)-Hexanediol was continuously produced over 5 days with a space-time yield of 64 g·L-1·d-1.
- Haberland, Juergen,Hummel, Werner,Daussmann, Thomas,Liese, Andreas
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- Biocatalytical production of (5S)-hydroxy-2-hexanone
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Biocatalytical approaches have been investigated in order to improve accessibility of the bifunctional chiral building block (5S)-hydroxy-2-hexanone ((S)-2). As a result, a new synthetic route starting from 2,5-hexanedione (1) was developed for (S)-2, whi
- Katzberg, Michael,Wechler, Kerstin,Mueller, Marion,Duenkelmann, Pascal,Stohrer, Juergen,Hummel, Werner,Bertau, Martin
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- On the mechanism of the unexpected facile formation of meso-diacetate products in enzymatic acetylation of alkanediols
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The mechanism of the unexpected facile formation of meso-diacetate previously observed in the enzymatic resolution of dl/meso mixtures of 2,4-pentanediol and 2,5-hexanediol with Candida antarctica lipase B has been elucidated. It was found that the formation of meso-diacetate proceeds via different mechanisms for the two diols. Enzyme-catalyzed acylation of AcO-d3 labeled (R)-monoacetates of meso-2,4-pentanediol and meso-2,5-hexanediol and analysis of the mesodiacetates obtained show that the former reaction proceeds via intramolecular acyl migration while the latter occurs via direct S-acylation of the alcohol. For the (R)-monoacetate of (R,S)-2,4-pentanediol the intramolecular acyl migration was fast and therefore direct S-acylation by the external acyl donor is suppressed. For the hexanediol monoacetate the rate ratio (pseudo E value) between (5R,2R)- and (5R,2S)-5-acetoxy-2-hexanol was experimentally determined to be kR,R/kR,S = 25, which is about 10-20 times lower than the E value for 2-pentanol and 2-octanol. In a preliminary experiment it was demonstrated that facile acyl migration in the 1,3-diol derivative can be utilized to prepare syn-1,3-diacetoxynonane (β90% syn) in high enantioselectivity (β99% ee) via a chemoenzymatic dynamic kinetic asymmetric tyransformation of a meso/dl mixture of 1,3-nonanediol.
- Edin, Michaela,Baeckvall, Jan-E.
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- Remote Asymmetric Induction. Stereo- and Enantioselective Synthesis of Symmetrical and Unsymmetrical 1,4-Diols
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Nucleophilic addition of Grignard reagents to the tricyclic lactols 4 or 5 provides with very high selectivity syn or anti 1,4-diols, so that, starting from the scalemic lactol 1a, three of the four possible diastereoisomeric 1,4-diols 7 or 9 can be obtained.This new example of remote asymmetric induction is illustrated by the synthesis of optically pure (2R,5R)-2,5-hexanediol and (3S,6R)-4-decen-3,6-diol.
- Bloch, Robert,Brillet, Cecile
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- Absolute configuration for 1, n-glycols: A nonempirical approach to long-range stereochemical determination
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The absolute configurations of 1,n-glycols (n = 2-12, 16) bearing two chiral centers were rapidly determined via exciton-coupled circular dichroism (ECCD) using a tris(pentafluorophenyl)porphyrin (TPFP porphyrin) tweezer system in a nonempirical fashion devoid of chemical derivatization. A unique "side-on" approach of the porphyrin tweezer relative to the diol guest molecule is suggested as the mode of complexation.
- Li, Xiaoyong,Burrell, Carmin E.,Staples, Richard J.,Borhan, Babak
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supporting information; experimental part
p. 9026 - 9029
(2012/07/13)
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- Dynamic kinetic asymmetric transformation of 1,4-diols and the preparation of trans-2,5-disubstituted pyrrolidines
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Dynamic kinetic asymmetric transformation (DYKAT) of a series of 1,4-diols is carried out with Candida antarctica lipase B (CALB), Pseudomonas cepacia lipase II (PS-C II), and a ruthenium catalyst. A β-chloro-substituted 1,4-diol is successfully transformed into an optically pure 1,4-diacetate, which is a highly useful synthetic intermediate. The usefulness of the optically pure 1,4-diacetates is demonstrated by the synthesis of enantiopure 2,5-disubstituted pyrrolidines.
- Borén, Linnéa,Leijondahl, Karin,B?ckvall, Jan-E.
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experimental part
p. 3237 - 3240
(2009/08/17)
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- A continuously operated bimembrane reactor process for the biocatalytic production of (2R,5R)-hexanediol
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Alcohol dehydrogenase-catalyzed reductions of prochiral ketones to chiral alcohols require the regeneration of consumed cofactors such as NADH or NADPH. In the substrate-coupled cofactor regeneration approach, where 2-propanol is oxidized to acetone, comp
- Schroer, Kirsten,Luetz, Stephan
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experimental part
p. 1202 - 1205
(2010/04/26)
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- Asymmetric anti-Prelog reduction of ketones catalysed by Paracoccus pantotrophus and Comamonas sp. cells via hydrogen transfer
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A broad range of ketones including methyl-aryl-, methyl-alkyl-, cyclic and sterically hindered ketones were reduced to the corresponding anti-Prelog alcohols with moderate to excellent stereoselectivities by employing lyophilised cells of Paracoccus pantotrophus DSM 11072 and Comamonas sp. DSM 15091 via hydrogen transfer. The reduction equivalents were provided using 2-propanol as a hydride donor. For instance, acetophenone was reduced to the corresponding (R)-enantiomer with >99% ee.
- Lavandera, Ivan,Hoeller, Brigitte,Kern, Alexander,Ellmer, Ursula,Glieder, Anton,de Wildeman, Stefaan,Kroutil, Wolfgang
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p. 1954 - 1958
(2008/12/22)
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- Highly efficient synthesis of enantiopure diacetylated C 2-symmetric diols by ruthenium- and enzyme-catalyzed dynamic kinetic asymmetric transformation (DYKAT)
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Highly efficient synthesis of enantiopure diacetates of 2,4-pentanediol and 2,5-hexanediol starting from commercially available mixtures of the diols (dl/ meso ≈1:1) has been realized by combining a fast ruthenium-catalyzed epimerization with an enzymatic transesterification. The in situ coupling of these two processes produces the diacetates in high yield in > 99 % enantiomeric excess.
- Martin-Matute, Belen,Edin, Michaela,Baeckvall, Jan-E.
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p. 6053 - 6061
(2007/10/03)
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- Regio- and stereoselective reduction of diketones and oxidation of diols by biocatalytic hydrogen transfer
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The asymmetric reduction of symmetrical and nonsymmetrical diketones as well as the stereoselective oxidation of various diols by biocatalytic hydrogen transfer was investigated by employing lyophilized cells of Rhodococcus ruber DSM 44541 containing alcohol dehydrogense ADH-'A'. Symmetrical and nonsymmetrical diketones at the (ω-1)- and (ω-2)-positions are reduced to the Prelog product with high stereopreference, while sterically more demanding ketone moieties, for example those at the (ω-3)-position, remain unchanged. For the oxidation mode, differentiation between primary and secondary alcohols is achieved, and the (S)-configured secondary alcohols at the (ω-1)- and (ω-2)-positions are oxidized preferentially. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Edegger, Klaus,Stampfer, Wolfgang,Seisser, Birgit,Faber, Kurt,Mayer, Sandra F.,Oehrlein, Reinhold,Hafner, Andreas,Kroutil, Wolfgang
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p. 1904 - 1909
(2007/10/03)
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- A short multigram asymmetric synthesis of prostanoid scaffolds
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Enantiomerically pure polysubstituted cyclopentanes which can be regarded as prostanoid scaffolds have been prepared by an efficient synthetic sequence readily applicable to the preparation of multigram quantities. The first key reaction is the diastereoselective allylmetallation of oxoamide 4 which is readily prepared from γ-butyrolactone and an enantiomerically pure 2,5-dimethylpyrrolidine. The second key-step is an intramolecular [2+2] cycloaddition of a keteneiminium salt leading to bicylo[3.2.0] heptanones. These intermediates have been easily transformed into a variety of prostanoid scaffolds of high enantiomeric purities.
- Depré, Dominique,Chen, Lian-Yong,Ghosez, Léon
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p. 6797 - 6812
(2007/10/03)
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- Asymmetric hydrosilylation of ketones using trans-chelating chiral peralkylbisphosphine ligands bearing primary alkyl substituents on phosphorus atoms
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Asymmetric hydrosilylation of simple ketones with diphenylsilane proceeded at -40 °C in the presence of a rhodium complex (0.001 - 0.01 molar amount) coordinated with a trans-chelating chiral bisphosphine ligand bearing linear alkyl substituents on the phosphorus atoms, (R,R)-(S,S)-Et-, Pr-, or BuTRAP, giving the corresponding optically active (S)- secondary alcohols with up to 97% ee. The asymmetric hydrosilylation using TRAP ligands with bulkier P-substituents resulted in much lower enantioselectivities. The EtTRAP-rhodium catalyst was also effective for asymmetric hydrosilylation of keto esters with a coordination site for a rhodium atom (up to 98% ee). Optically active symmetrical diols were obtained with up to 99% ee from the corresponding diketones via the asymmetric reduction using 2.5 molar amounts of diphenylsilane.
- Kuwano, Ryoichi,Sawamura, Masaya,Shirai, Junya,Takahashi, Masatoshi,Ito, Yoshihiko
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p. 485 - 496
(2007/10/03)
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- Oxazaborolidine-catalysed reduction of alk-2-ene-1,4-diones. A convenient access to chiral 1,4-diols
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An efficient method for the preparation of C2-symmetric, chiral alk-2- ene-1,4-diols (4) has been achieved, based on the borane-mediated reduction of symmetric alk-2-ene-1,4-diones (2) in the presence of oxazaborolidine (R)- 1. In general, the presence of the double bond in 2 has been beneficial (compared with the related saturated 1,4-diketones 3) not only as far as the stereoselectivity in the reduction step is concerned, but also because it allowed us to remove meso-4 by chomatography and/or to improve the stereochemical purity of several resulting mixtures of diols 4 by Sharpless' epoxidation. Enantioenricbed compounds 4 have been readily reduced to saturated diols with negligible loss of optical purity.
- Bach, Jordi,Berenguer, Ramon,Garcia, Jordi,Lopez, Marta,Manzanal, Judith,Vilarrasa, Jaume
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p. 14947 - 14962
(2007/10/03)
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- Stereoselective reduction of unsaturated 1,4-diketones. A practical route to chiral 1,4-diols
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A new synthetic route to C2-symmetric chiral 1,4-diols based on the borane-mediated oxazaborolidine-catalysed reduction of 2-ene-1,4-diones (2), of 2-yne-1,4-diones (3), and/or of Co-complexed diketones 4 is described. Good to excellent enantio- and diastereoselectivities have been obtained in the reduction of diketones 3 and 4, catalysed by oxazaborolidines 6 and 5, respectively.
- Bach, Jordi,Berenguer, Ramon,Garcia, Jordi,Loscertales, Teresa,Manzanal, Judith,Vilarrasa, Jaume
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p. 1091 - 1094
(2007/10/03)
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- Yeast-mediated synthesis of optically active diols with C2-symmetry and (R)-4-pentanolide
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Reduction of some diketones and a keteacid with yeast, Pichia farinosa IAM 4682 was examined. The reduction of carbonyl groups proceeded highly selectively with an anti-Prelog fashion to give (R)-alcohols. (2R,5R)2,5- Hexanediol (83% yd., >99% e.e., 95% d.e.), (2R,4R)-2,4-pentanediol (94% yd., >99% e.e., 98% d.e.), and (R)-4-pentanolide (67% yd., >99% e.e.) were highly efficiently obtained from the corresponding ketones. Effect of the structure of substrate on the stereochemical course as well as the selectivity were discussed.
- Ikeda,Sato,Sugai,Ohta
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p. 8113 - 8122
(2007/10/03)
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- Asymmetric Hydrosilylation of Symmetrical Diketones Catalyzed by a Rhodium Complex with Trans-Chelating Chiral Diphosphine EtTRAP
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Asymmetric hydrosilylation of symmetrical diketones with diphenylsilane in the presence of catalytic amount (/ = 100> of rhodium complex coordinated with trans-chelating chiral phosphine ligand EtTRAP gave corresponding optically active symmetrical diols with high enantiomeric excesses.
- Kuwano, Ryoichi,Sawamura, Masaya,Shirai, Junya,Takahashi, Masatoshi,Ito, Yoshihiko
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p. 5239 - 5242
(2007/10/02)
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- Asymmetric synthesis of both enantiomers of 2.5-hexane diol and 2.6-heptane diol induced by chiral sulfoxides
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both enantiomers of 2,5-hexane diol and 2,6-heptane diol have been prepared respectively by stereoselective reduction of optically active diketodisulfoxides and ketosulfoxides.
- Solladie, Guy,Huser, Nathalie,Garcia-Ruano, Jose Luis,Adrio, Javier,Carmen Carreno,Tito, Amelia
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p. 5297 - 5300
(2007/10/02)
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- Preparation of optically active hydrazines and amines
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A process for the asymmetric hydrogenation of N-acylhydrazones to optically active N-acylhydrazines in the presence of a chiral phospholane catalyst complex, a process for the reductive N--N bond cleavage of N-acylhydrazine to amines with samarium diiodide, and a multistep process for converting keto group-bearing compounds to the corresponding optically active amino group-bearing compounds are disclosed.
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- Chiral phospholanes via chiral 1,4-diol cyclic sulfates
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This invention relates to novel chiral 1,4-diol cyclic sulfates and their use as precursors in the preparation of chiral phospholane ligands, and chiral complexes useful as catalysts for carrying out enantioselective reactions.
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- New chiral phospholanes; synthesis, characterization, and use in asymmetric hydrogenation reactions
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We describe the practical synthesis of enantiomerically pure trans-2,5-disubstituted-1-phenylphospholanes which are then employed in the preparation of a new series of C2-symmetric bis- and C3-symmetric tris(phospholane) ligands. A versatile three-step route to the important chiral 1,4-diol intermediates, used in the phosphine syntheses, is outlined. Rhodium complexes bearing the new phosphine ligands were prepared and shown to act as efficient catalyst precursors for the enantioselective hydrogenation of various unsaturated substrates.
- Burk,Feaster,Harlow
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p. 569 - 592
(2007/12/18)
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