- Optical resolution of medium-size lactones by inclusion crystallization with optically active host compounds: remarkable odd-even effects on the chiral recognition
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Molecular recognition of medium-size lactones by inclusion complexation with optically active hosts derived from tartaric acid is described. Odd-even effects on the chiral recognition were observed in the enantioselective inclusion with the optically active host compounds in the solid state.
- Tanaka, Koichi,Kuchiki, Daisuke,Caira, Mino R.
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- Iridium-Catalyzed Asymmetric Hydrogenation of ?- A nd ?-Ketoacids for Enantioselective Synthesis of ?- A nd ?-Lactones
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A highly efficient asymmetric hydrogenation of ?- A nd ?-ketoacids was developed by using a chiral spiro iridium catalyst (S)-1a, affording the optically active ?- A nd ?-hydroxy acids/lactones in high yields with excellent enantioselectivities (up to >99% ee) and turnover numbers (TON up to 100000). This protocol provides an efficient and practical method for enantioselective synthesis of Ezetimibe.
- Hua, Yun-Yu,Bin, Huai-Yu,Wei, Tao,Cheng, Hou-An,Lin, Zu-Peng,Fu, Xing-Feng,Li, Yuan-Qiang,Xie, Jian-Hua,Yan, Pu-Cha,Zhou, Qi-Lin
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supporting information
p. 818 - 822
(2020/02/15)
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- Kinetic resolution of racemic hydroxy ester via asymmetric catalytic hydrogenation and application thereof
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The present invention relates to kinetic resolution of racemic δ-hydroxyl ester via asymmetric catalytic hydrogenation and an application thereof. In the presence of chiral spiro pyridyl phosphine ligand Iridium catalyst and base, racemic δ-hydroxyl esters were subjected to asymmetric catalytic hydrogenation to obtain extent optical purity chiral δ-hydroxyl esters and corresponding 1,5-diols. The method is a new, efficient, highly selective, economical, desirably operable and environmentally friendly method suitable for industrial production. An optically active chiral δ-hydroxyl ester and 1,5-diols can be obtained at very high enantioselectivity and yield with relatively low usage of catalyst. The chiral δ-hydroxyl ester and 1,5-diols obtained by using the method can be used as a critical raw material for asymmetric synthesis of chiral drugs (R)-lisofylline and natural drugs (+)-civet, (?)-indolizidine 167B and (?)-coniine.
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- Biocatalytic Characterization of Human FMO5: Unearthing Baeyer-Villiger Reactions in Humans
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Flavin-containing mono-oxygenases are known as potent drug-metabolizing enzymes, providing complementary functions to the well-investigated cytochrome P450 mono-oxygenases. While human FMO isoforms are typically involved in the oxidation of soft nucleophiles, the biocatalytic activity of human FMO5 (along its physiological role) has long remained unexplored. In this study, we demonstrate the atypical in vitro activity of human FMO5 as a Baeyer-Villiger mono-oxygenase on a broad range of substrates, revealing the first example to date of a human protein catalyzing such reactions. The isolated and purified protein was active on diverse carbonyl compounds, whereas soft nucleophiles were mostly non- or poorly reactive. The absence of the typical characteristic sequence motifs sets human FMO5 apart from all characterized Baeyer-Villiger mono-oxygenases so far. These findings open new perspectives in human oxidative metabolism.
- Fiorentini, Filippo,Geier, Martina,Binda, Claudia,Winkler, Margit,Faber, Kurt,Hall, Mélanie,Mattevi, Andrea
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p. 1039 - 1048
(2016/05/19)
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- Remote ester group leads to efficient kinetic resolution of racemic aliphatic alcohols via asymmetric hydrogenation
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A highly efficient method for kinetic resolution of racemic aliphatic alcohols without conversion of the hydroxyl group has been realized; the method involves hydrogenation mediated by a remote ester group and is catalyzed by a chiral iridium complex. This powerful, environmentally friendly method provides chiral δ-alkyl-δ-hydroxy esters and δ-alkyl-1,5-diols in good yields with high enantioselectivities even at extremely low catalyst loading (0.001 mol %).
- Yang, Xiao-Hui,Wang, Ke,Zhu, Shou-Fei,Xie, Jian-Hua,Zhou, Qi-Lin
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p. 17426 - 17429
(2015/02/02)
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- Stereodivergent preparation of valuable γ- Or δ-hydroxy esters and lactones through one-pot cascade or tandem chemoenzymatic protocols
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A series of enantiopure hydroxy esters and lactones has been synthesized in a chemodivergent manner via alcohol dehydrogenase (ADH) reduction of the corresponding keto esters by means of cascade or tandem protocols. Thus, ADH from Rhodococcus ruber (ADH-A) or Lactobacillus brevis (LBADH) afforded both antipodes in a very selective way when dealing with small derivatives. With bulkier substrates, ADH from Ralstonia sp. (RasADH) was successfully employed to achieve the synthesis of enantioenriched γ- or δ-hydroxy esters. To isolate the corresponding lactones, two different approaches were followed: a cascade reaction by spontaneous cyclization of the hydroxy ester intermediate, or a one-pot two-step tandem protocol. Moreover, a chemoenzymatic route was designed to obtain a chiral brominated lactone, which enabled further modifications in a sequential fashion by Pd-catalyzed reactions, affording relevant functionalized lactones.
- Diaz-Rodriguez, Alba,Borzeicka, Wioleta,Lavandera, Ivan,Gotor, Vicente
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p. 386 - 393
(2014/03/21)
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- Enantioselective route to ketones and lactones from exocyclic allylic alcohols via metal and enzyme catalysis
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A general and efficient route for the synthesis of enantiomerically pure α-substituted ketones and the corresponding lactones has been developed. Ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR) with a subsequent Cu-catalyzed α-allylic substitution are the key steps of the route. The α-substituted ketones were obtained in high yields and with excellent enantiomeric excess. The methodology was applied to the synthesis of a naturally occurring caprolactone, (R)-10-methyl-6-undecanolide, via a subsequent Baeyer-Villiger oxidation.
- Warner, Madeleine C.,Nagendiran, Anuja,Bogár, Krisztián,B?ckvall, Jan-E.
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p. 5094 - 5097
(2013/01/15)
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- Chemoenzymatic synthesis of (2R)-2-hydroxyundecan-6-one
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Optimisation of kinetic resolution of racemic 5-hydroxyhexanenitrile (2) was performed; acetylation with vinyl acetate, catalyzed by Pseudomonas cepacia lipase immobilized on ceramics (PS-C) in n-hexane, afforded (5R)-acetoxy-hexanenitrile [(R)-3] with 94% ee and 94% yield; E = 83. Deacetylation of (R)-3, protection of (R)-2 by tert-butyldimethylsilyl group, Grignard reaction of (R)-4 with n-pentyl magnesium bromide, and final deprotection of (R)-5 afforded the title compound (R)-6 in 32% overall yield from 1 and 94% enantiomeric purity. Absolute configuration of (R)-6 was assigned by chemical correlations to (5R)-methyl-5-pentanolide [(R)-7].
- Ljubovic,Sunjic
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p. 423 - 426
(2007/10/03)
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- Potential and Limitations of Palladium-Cinchona Catalyst for the Enantioselective Hydrogenation of a Hydroxymethylpyrone
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The palladium-catalyzed enantioselective hydrogenation of 4-hydroxy-6-methyl-2-pyrone afforded up to 85% excess to the (S)-enantiomer of the corresponding 5,6-dihydropyrone, under very mild conditions (1 bar, room temperature). This is the highest enantioselectivity achieved so far with chirally modified Pd, demonstrating the potential of this catalyst in the enantioselective hydrogenation of unsaturated compounds. A complicating feature of the reaction is the limited stability of cinchonidine under reaction conditions, which results in a decline of the initial enantiomeric excess (ee) with reaction time. Continuous feeding of a minute amount of cinchonidine during reaction allows maintenance of the high initial ee with an overall substrate/modifier molar ratio of ca. 20.
- Huck,Mallat,Baiker
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- Applications of highly enantioenriched alcohols bearing a phenylthio group in the preparation of ring compounds. The two-pot synthesis of an enantiopure spiroacetal pheromone bearing three chiral centers
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The new chiron (S)-6-phenylthio-2-hexanol (3) was prepared in high enantiomeric excess by baker's yeast reduction of the corresponding ketone. Enantioenriched alcohols 1, 2 and 3, prepared previously by a similar procedure, or their racemic counterparts, were transformed into ring closed compounds 5-methyl-2-(phenylthio)tetrahydrofuran (9), 6-methyl-2- (phenylthio)tetrahydropyran (10), 2-methyl-1-phenylsulfonyl cyclopropane (14), cyclobutane (15), cyclopentane (16), and a bee pheromone, (2S,6R,8S)- 2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (20).
- Cohen, Theodore,Tong, Shaojing
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p. 9487 - 9496
(2007/10/03)
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- Asymmetric Hydrogenation of Olefins with Aprotic Oxygen Functionalities Catalyzed by BINAP-Ru(II) Complexes
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Cyclic α,β-unsaturated ketones, alkylidene lactones, and alkenyl ethers have been hydrogenated in high enantiomeric excesses by use of BINAP-Ru(II) complexes (BINAP = 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) as catalysts. 2-Alkylidenecyclopentanones were hydrogenated in the presence of Cl, Ru2Cl4(BINAP)2(NEt3), or Ru(OCOCH3)2(BINAP) in up to 98percent ee, while in the case of 2-benzylidene- and 2-(3-phenylpropylidene)cyclopentanones, enantiomeric excesses of the hydrogenation were below 50percent under the same conditions.The sense of asymmetric induction as well as the enantioselectivity (95percent ee) obtained in the hydrogenation of (E)-2-propylidene-γ-butyrolactone were the same as those of the (Z)-isomer.Lactones, 2- and 4-alkylidene-γ-butyrolactones, were converted to the corresponding saturated γ-butyrolactones in 95percent ee.Hydrogenation of diketene with the catalytic system derived from (benzene)>Cl and triethylamine or complex Ru2Cl42(NEt3) established a new synthetic route to (R)-4-methyl-2-oxetanone, a promising monomer of biodegradable polymers, in up to 97percent selectivity and 92percent ee.Alkenyl ethers, 2-methylenetetrahydrofuran, and 2-methyl-3,4-dihydrofuran have also been hydrogenated to give 2-methyltetrahydrofuran in 91 and 87percent ee, respectively.
- Ohta, Tetsuo,Miyake, Tsutomu,Seido, Nobuo,Kumobayashi, Hidenori,Takaya, Hidemasa
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p. 357 - 363
(2007/10/02)
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- Asymmetric Hydrogenation of 3,5-Dioxoesters Catalyzed by Ru-binap Complex: A Short Step Asymmetric Synthesis of 6-Substituted 5,6-dihydro-2-pyrones
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Asymmetric hydrogenation of 3,5-dioxoesters 1a-c using Ru2Cl4((R) or (S)-binap)2(NEt3) as the catalyst gave dominantly anti 3,5-dihydroxyesters 2, which were then converted into unsaturated lactones 5a-b (ca. 80percent e.e.).The pathway of the hydrogenation reaction was also investigated by asymmetric hydrogenation of (R)- or (S)-5-hydroxy-3-oxoesters 8a-c.It was revealed that the Ru-binap catalyzed hydrogenation of 1a-b proceed dominantly via the β-diketone mode.A convenient asymmetric synthesis of hydroxylactone 3c and unsaturated lactone 5c was presented.Key words: 3,5-dioxoester; Ru-binap catalyst; asymmetric hydrogenation; asymmetric synthesis; lactone
- Shao, Liming,Kawano, Hiroyuki,Saburi, Masahiko,Uchida, Yasuzo
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p. 1997 - 2010
(2007/10/02)
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- Degradation and Absolute Configurational Assignment to C34-Botryococcene
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C34-Botryococcene, the major hydrocarbon constituent of the B race of Botryococcus braunii, was degraded by ozonolysis of its dihydro derivative followed by Baeyer-Villiger oxidation to γ-valerolactone, 2,5-dimethylhexanolactone, and 2-ethyl-2,
- White, James D.,Somers, Todd C.,Reddy, G. Nagabushana
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p. 4991 - 4998
(2007/10/02)
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- SYNTHESIS OF ENANTIOMERICALLY PURE (S)-5,6-DIHYDRO- AND (S)-TETRAHYDRO-6-METHYL-2H-PYRAN-2-ONE
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An efficient synthesis of enantiomerically pure (S)-5,6-dihydro-6-methyl-2H-pyran-2-one, 6, and (S)-tetrahydro-6-methyl-2H-pyran-2-one, 7, from (S)-1-(1,3-dithian-2-yl)-2-hydroxypropane, is reported.
- Bernardi, Rosanna,Ghiringhelli, Dario
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p. 395 - 396
(2007/10/02)
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- Enantiospecific routes to 3,4 disubstituted azetidinones
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Enantiospecific routes to 3,4 disubstituted azetidinones are outlined which commence with readily available β-ketoester precursors.
- Kahn,Fujita
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p. 1137 - 1144
(2007/10/02)
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- Bakers' yeast reduction of γ and δ ketonitriles: Intermediates for the synthesis of (S)-5-hexanolide and other chiral lactones
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A number of γ and δ ketonitriles have been synthesized and their reduction with bakers' yeast carefully studied. Both 4-oxopentanenitrile and 5-oxohexanenitrile are reduced in moderate yields to the corresponding (S) alcohols of high ee while other substrates gave products of varying optical purities. These alcohols are useful intermediates for the preparation of chiral lactones, including the synthetically important (S)(-)-4-methylbutyrolactone and (S)-5-hexanolide.
- Gopalan,Lucero,Jacobs,Berryman
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p. 1321 - 1329
(2007/10/02)
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- Synthesis of 1,3-dioxin-4-ones having chiral hydroxyalkyl groups at the 6-position by means of baker's yeast reduction and their uses for epc synthesis
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Prochiral methyl ketones connected with 6-(4-oxo-1,3-dioxinyl) group directly or through methylene chain (1-3) gave, by treatment with fermenting baker's yeast, the corresponding (S)-alcohols which served as synthons for a variety of enantiomerically pure
- Sakaki, Jun-Ichi,Sugita, Yoshiaki,Sato, Masayuki,Kaneko, Chikara
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p. 6197 - 6214
(2007/10/02)
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- Asymmetric Hydrogenation of Methyl 3,5-Dioxohexanoate Catalyzed by Ru-binap Complex: A Short Step Asymmetric Synthesis of Dihydro-6-methyl-2H-pyran-2-one
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Hydrogenation of methyl 3,5-dioxohexanoate 3 using Ru2Cl4((R) or (S)-binap)2(NEt3) as the catalyst gave dominantly anti 3,5-dihydroxyester 9, which was then converted into unsaturated lactone 4.The pathway of the hydrogenation reaction was also investigated. Key words: β,δ-diketonester; Ru-binap catalyst; asymmetric hydrogenation; asymmetric synthesis; lactone.
- Shao, Liming,Seki, Toshiyuki,Kawano, Hiroyuki,Saburi, Masahiko
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p. 7699 - 7702
(2007/10/02)
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- Highly enantioselective reduction of acetoacetylated Meldrum's acid with fermenting baker's yeast
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Acetoacetylated Meldrum's acid was enantioselectively reduced with fermenting baker's yeast to afford the corresponding chiral (S)-alcohol, which could be easily converted to δ-lactone derivatives.
- Sato,Sakaki,Sugita,Nakano,Kaneko
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p. 7463 - 7466
(2007/10/02)
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- Enantioselective syntheses of (R)-(+)-δ-methyl-δ-valerolactone and (R)-(+)-6-methyl-ω-lactone
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Enantioselective syntheses of (R)-(+)-δ-methyl-δ-valerolactone (1) and (R)-(+)-6-methyl-ω-lactone (2) are reported using (R)-(-)-2-amino-n-dibutyl ether (3) as an enamine complexing agent in the chiral synthesis.
- Gadkari,Kapadi
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p. 407 - 408
(2007/10/02)
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- Enzymatic Resolution of Medium-Ring Lactones. Synthesis of (S)-(+)-Phoracantholide I
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The horse liver and pig liver esterase hydrolysis of racemic medium ring lactones gives with excellent enantiomeric excess the S- (or R) lactones and the corresponding R- (or S) hydroxy acids.This is the first general method to obtain optically pure medium ring lactones.Application to the preparation of (S)-(+)-Phoracantholide I is reported.
- Fouque, Elie,Rousseau, Gerard
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p. 661 - 666
(2007/10/02)
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- Biosyntheses of Antibiotic A26771B by Penicillium turbatum and Dehydrocurvularin by Alternaria cinerariae: Comparison of Stereochemistry of Polyketide and Fatty Acid Enoyl Thiol Ester Reductases
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The biosyntheses of reduced polyketides and fatty acids were compared by use of stable isotope labeling and NMR spectroscopy.Incorporations of sodium -, -, -, -, -, and acetates i
- Arai, Kunizo,Rawlings, Bernard J.,Yoshizawa, Yuko,Vederas, John C.
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p. 3391 - 3399
(2007/10/02)
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- Catalytic Asymmetric Synthesis of Alkyl Substituted Lactones by Enantioselective and Chemoselective Alkylation of Formylesters with Dialkylzincs Using N,N-Dibutylnorephedrine
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Optically active 4-alkyl-γ-butyrolactones and 5-alkyl-6-valerolactones were obtained in high enantiomeric excesses (85-95percent e.e.) from the catalytic asymmetric alkylation of 3- and 4-formylesters with dialkylzincs using N,N-dibutylnorephedrine as catalyst.
- Soai, Kenso,Yokoyama, Shuji,Hayasaka, Tomoiki,Ebihara, Katsumi
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p. 843 - 846
(2007/10/02)
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- CHEMISTRY OF BAKER'S YEAST REDUCTION PRODUCTS: USE OF OPTICALLY ACTIVE (S)-(+)-1-(p-TOLUENESULFONYL)PROPAN-2-OL AND (S)-(+)-1-(PHENYLSULFONYL)PROPAN-2-OL IN SYNTHESIS.
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The utility of the title compounds in the preparation of optically active lactones and alcohols is detailed.
- Kozikowski, Alan P.,Mugrage, B.B.,Li, C.S.,Felder, L.
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p. 4817 - 4820
(2007/10/02)
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- A Convenient Synthesis of δ-Lactones
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Direct lithiation of β-ethylthio- and β-phenylthioacrylic acid affords β-lithiopropionate equivalents.The usefulness of these reagents is demonstrated in a convenient synthesis of α,β-unsaturated δ-lactones and their transformation into the corresponding saturated δ-lactones.The required reaction with epoxides as electrophiles was promoted by addition of boron trifluoride-ether.
- Barua, Nabin C.,Schmidt, Richard R.
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p. 1067 - 1070
(2007/10/02)
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- Chirale Synthesebausteine durch Kolbe-Elektrolyse enantiomerenreiner β-Hydroxy-carbonsaeurederivate, (R)- und (S)-Methyl- sowie (R)-Trifluormethyl-γ-butyrolactone und δ-valerolactone
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The coupling of chiral, non-racemic R* groups by Kolbe electrolysis of carboxylic acids R*COOH is used to prepare compounds with a 1,4- and 1,5-distance of the functional groups.The suitably protected β-hydroxycarboxylic acids (R)- or (S)-3-hydroxybutyric acid, (R)-4,4,4-trifluoro-3-hydroxybutyric acid (as acetates; see 1-6), and (S)-malic acid (as (2S,5S)-2-(tert-butyl)-5-oxo-1,3-dioxolan-4-acetic acid, see 7) are decarboxylatively dimerized or "codimerized" with 2-methylpropanoic acid, with 4-(formylamino)butyric acid, and with monomethyl malonate and succinate.The products formed are derivatives of (R,R)-1,1,1,6,6,6-hexafluoro-2,5-hexanediol (see 8), of (R)-5,5,5-trifluoro-4-hydroxypentanoic acid (see 9, 10), of (R)- and (S)-5-hydroxyhexanoic acid (see 11) and its trifluoro analogue (see 12, 13), of (S)-2-hydroxy- and (S,S)-2,5-dihydroxyadipic acid (see 23, 20), of (S)-2-hydroxy-4-methylpentanoic acid ("OH-leucine", see 21), and of (S)-2-hydroxy-6-aminohexanoic acid ("OH-lysine", see 22).Some of these products are further converted to CH3- or CF3-substituted γ- and δ- lactones of (R)- or (S)-confuguration (14, 16-19), or to an enantiomerically pure derivative of (R)-1-hydroxy-2-oxocyclopentane-1-carboxylic acid (see 24).Possible uses of these new chiral building blocks for the synthesis of natural products and their CF3 analogues (brefeldin, sulcatol, zearalenone) are discussed.The olfactory properties of (R)- and (S)-δ-caprolactone (18) are compared with those of (R)-6,6,6-trifluoro-δ-caprolactone (19).
- Seebach, Dieter,Renaud, Philippe
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p. 2342 - 2349
(2007/10/02)
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- SYNTHESIS OF THE ENANTIOMERS OF CIS-2-METHYL-5-HEXANOLIDE, THE MAJOR COMPONENT OF THE SEX PHEROMONE OF THE CARPENTER BEE
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(2R,5S)-2-Methyl-5-hexanolide and its antipode were synthesized in highly optically pure state (98-99percent e.e.) starting from ethyl (S)-lactate and the enantiomers of methyl β-hydroxyisobutyrate.The specific rotations of our samples were D +/- 91.0 -93.5 deg (CHCl3), while the reported values of the samples prepared by resolution or asymmetric synthesis were +/- 64.5-65.6 deg.
- Mori, Kenji,Senda, Shuji
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p. 541 - 546
(2007/10/02)
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- LIGHT-INDUCED FREE-RADICAL REACTIONS OF 2-METHOXY-6-METHYLTETRAHYDROPYRAN: IRREVERSIBLE RING OPENING AND MULTISITE HYDROGEN ABSTRACTION
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Acetophenone-initiated photodegradation of cis-2-methoxy-4-methyltetrahydropyran (7) in benzene solvent produced six products.The structures of the products, and studies using optically active 7, showed that hydrogen abstraction occurs at both C-2 and C-6 of the tetrahydropyran ring.The products derived from the C-2 radical indicated two pathways for this radical: ring opening and loss of methyl, which is consistent with previous work on other similar systems.Results with optically active 7 showed that the ring-opening pathway is irreversible.Generation of an open-chain radical independently also showed that cyclization to a six membered ring does not occur.The products from the photodegradation were trans-2-methoxy-6-methyltetrahydropyran (8), methyl hexanoate (10), 6-methyltetrahydropyran-2-one (9), methyl 5-phenylhexanoate (11), 1,7-dimethyl-7-phenyl-6,8-dioxobicyclooctane (13), and 2-methoxy-2-(1-phenyl-1-hydroxyethyl)-6-methyltetrahydropyran (12).The yield of lactone 9 was found to be sensitive to the amount of residual oxygen present during the photolysis.
- Babcock, Bruce W.,Dimmel, Donald R.,Graves, David P.,McKelvey, Ronald D.
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p. 736 - 742
(2007/10/02)
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