- Synthesis of 2,4-Dimethylglutaric Acid Monoesters via Enzyme-catalyzed Asymmetric Alcoholysis of meso-2,4-Dimethylglutaric Anhydride
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1-(2-Methylpropyl) 5-hydrogen (2R,4S)-2,4-dimethylpentanedioate with an enantiomeric excess of 90percent was obtained in a yield of 72percent from meso-2,4-dimethylpentanedioic anhydride and 2-methylpropanol by an asymmetric alcoholysis catalyzed by the l
- Ozegowski, Ruediger,Kunath, Annamarie,Schick, Hans
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- Preparation of Useful Chiral Lactone Synthons via Stereospecific Enzyme-catalysed Oxidations of meso-Diols
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Horse liver alcohol dehydrogenase-catalysed oxidations of symmetrical acyclic and cyclic meso-diol substrates give chiral γ- and δ-lactones in high yields and of 100percent enantiomeric excess and provide access to a broad range of useful synthons of value in asymmetric syntheses of natural products.
- Jakovac, Ignac J.,Ng, George,Lok, Kar P.,Jones, J. Bryan
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- Desymmetrization of acid anhydride with asymmetric esterification catalyzed by chiral phosphoric acid
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Asymmetric desymmetrization of σ-symmetric acid anhydrides was achieved with chiral phosphoric acid as a Br?nsted acid catalyst. The key of success was finding of benzhydrol and 2,2-diphenylethanol as the nucleophiles of choice. The corresponding half esters were obtained in good yields with high selectivity.
- Yamada, Ken-ichi,Oonishi, Akinori,Kuroda, Yusuke,Harada, Shingo,Kiyama, Hiroki,Yamaoka, Yousuke,Takasu, Kiyosei
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supporting information
p. 4098 - 4100
(2016/08/18)
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- Intramolecular stereoselective protonation of aldehyde-derived enolates
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Picking sides: Asymmetric protonation of the titled compounds poses a most significant challenge and has been addressed by taking advantage of internal protonation and subsequent hemiacetal formation to avoid epimerization (see scheme). The substrates employed in these transformations can be easily accessed through a sequence of vinylogous aldol reactions with subsequent conjugate reductions.
- Kena-diba, Anastasie,Noll, Claudia,Richter, Michael,Gieseler, Marc Timo,Kalesse, Markus
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supporting information; experimental part
p. 8367 - 8369
(2010/12/25)
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- Remote control of regio- and diastereoselectivity in the hydroformylation of bishomoallylic alcohols with catalytic amounts of a reversibly bound directing group
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(Figure Presented) Remote and reversible! Phosphinites serve as reversibly bound directing groups for the remote control of the regio- and diastereoselective hydroformylation of bishomoallylic alcohols (see scheme; r.r: regioisomer ratio). The distance between the double bond and the functional hydroxy group to which the directing group is reversibly bound is the longest ever reported.
- Gruenanger, Christian U.,Breit, Bernhard
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supporting information; experimental part
p. 967 - 970
(2010/05/02)
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- Total Synthesis of rapamycin
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For over 30 years, rapamycin has generated a sustained and intense interest from the scientific community as a result of its exceptional pharmacological properties and challenging structural features. In addition to its well known therapeutic value as a potent immunosuppressive agent, rapamycin and its derivatives have recently gained prominence for the treatment of a wide variety of other human malignancies. Herein we disclose full details of our extensive investigation into the synthesis of rapamycin that culminated in a new and convergent preparation featuring a macro-etherification/catechol-templating strategy for construction of the macrocyclic core of this natural product.
- Ley, Steven V.,Tackett, Miles N.,Maddess, Matthew L.,Anderson, James C.,Brennan, Paul E.,Cappi, Michael W.,Heer, Jag P.,Helgen, Celine,Kori, Masakuni,Kouklovsky, Cyrille,Marsden, Stephen P.,Norman, Joanne,Osborn, David P.,Palomero, Maria A.,Pavey, John B. J.,Pinel, Catherine,Robinson, Lesley A.,Schnaubelt, Juergen,Scott, James S.,Spilling, Christopher D.,Watanabe, Hidenori,Wesson, Kieron E.,Willis, Michael C.
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supporting information; experimental part
p. 2874 - 2914
(2009/12/25)
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- Asymmetric hydrogenation routes to deoxypolyketide chirons
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Asymmetric hydrogenations of monoenes and dienes were performed to obtain terminal deoxypolyketide fragments A and the corresponding internal Chirons B and C. The chiral N-heterocyclic carbene catalyst 1 was used throughout. Modest selectivities for hydrogenations of simple monoenes relayed into high selectivities for preparations of the terminal deoxypolyketide fragments in which either two hydrogenations or one and an optically pure starting material were used. Curiously, the face selectivities for hydrogenation of α,β-unsaturated esters were consistently opposite to those that had been observed for styrene and stilbene derivatives in previous work, and to closely related allylic alcohol and ether derivatives in this work. Plausible mechanisms for this differing behavior were deduced by using DFT calculations. It appears that the origin of the unusual stereoselectivity for the ester derivatives is transient metal-coordination of the ester carbonyl whereas there is no evidence that the allylic alcohol or ethers coordinate. The routes developed to α,ω-functionalized internal deoxypolyketide fragments are extremely practical. These begin with the Roche ester being converted into alkene and, in one case, diene derivatives. Catalyst control prevails in the hydrogenations of these substrates, but there is a significant "substrate vector" (a term we used to describe the influence of the substrate on a catalyst-controlled reaction). This is determined by minimization of 1,3-allylic strain and, in some cases, syn pentane interactions. This substrate vector can be constructively paired with the (dominant) catalyst vector by use of the appropriate enantiomer of 1. In the hydrogenation of a diene derivative, two chiral centers could be formed simultaneously with overall 11:1.0 selectivity; this is the first time this has been achieved in any asymmetric synthesis of a deoxypolyketide fragment. Throughout, diastereo-selectivities of the crude material in the syntheses of α,ω-functionalized internal deoxypolyketide fragments were in excess of 11:1.0 and chromatographically purified samples could be isolated in high yields with dr (dr = diastereomeric ratio) values consistently in excess of 40:1.0.
- Zhou, Jianguang,Ogle, James W.,Fan, Yubo,Banphavichit, Yorawit,Zhu, Ye,Burgess, Kevin
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p. 7162 - 7170
(2008/03/12)
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- Highly enantioselective catalytic thiolysis of prochiral cyclic dicarboxylic anhydrides utilizing a bifunctional chiral sulfonamide
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(Chemical Equation Presented) A catalytic desymmetrization is achieved for various prochiral dicarboxylic anhydrides with yields of 87-100% and ee values of 83-98% through the title reaction (see scheme; Bn = benzyl). The bifunctional effect of the chiral sulfonamide catalyst was clarified on the basis of unsuccessful asymmetric induction by using the related chiral sulfonamides.
- Honjo, Takashi,Sano, Shigeki,Shiro, Motoo,Nagao, Yoshimitsu
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p. 5838 - 5841
(2007/10/03)
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- A Diels-Alder macrocyclization enables an efficient asymmetric synthesis of the antibacterial natural product abyssomicin C
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An efficient and highly diastereoselective intramolecular Diels-Alder reaction is the basis of a concise asymmetric synthesis of the potent antibacterial natural product abyssomicin C (see formula). The complexity of the target structure was reduced to three fragments and required two carbonyl addition reactions to achieve key bond formations. (Figure Presented).
- Zapf, Christoph W.,Harrison, Bryce A.,Drahl, Carmen,Sorensen, Erik J.
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p. 6533 - 6537
(2007/10/03)
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- All-catalytic, efficient, and asymmetric synthesis of α,ω- diheterofunctional reduced polypropionates via "one-pot" Zr-catalyzed asymmetric carboalumination - Pd-catalyzed cross-coupling tandem process
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A highly efficient method for the synthesis of stereochemically pure (≥99% ee and >50/1 dr) α,ω-diheterofunctional reduced polypropionates has been developed. The essential features of the method are represented by the conversion of inexpensive styrene in
- Novak, Tibor,Tan, Ze,Liang, Bo,Negishi, Ei-Ichi
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p. 2838 - 2839
(2007/10/03)
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- Synthetic routes to the stereoisomers of 2,4-dimethylpentane-1,5-diol derivatives
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Five different routes to every stereoisomer of non-symmetric derivatives of 2,4-dimethylpentanedioic acid and/or of O-monoprotected 2,4-dimethylpentane- 1,5-diols, which are common building blocks for the total synthesis of many polypropionates, have been investigated. Alkylation of the lithium enolate of N-propanoylpseudoephedrine turned out to be the most appropriate method, in connection with the synthesis of fragment C1-C5 of amphidinolide K.
- Mas, Gemma,González, Llu?sa,Vilarrasa, Jaume
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p. 8805 - 8809
(2007/10/03)
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- Toward a total synthesis of okilactomycin. 1. A direct, enantiocontrolled route to the western sector
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A synthesis of the western half of the macrocyclic ring framework of the antitumor antibiotic okilactomycin is described. The strategy employed rests on an efficient synthesis of meso-2,4-dimethylglutaric anhydride and ensuing resolution via reaction with (S)-(-)-α-methylbenzylamine, diborane reduction, and selective crystallization. Following acid-catalyzed cyclization to (2S,4R)-2,4-dimethyl-δ-valerolactone, an acyclic stereocontrol strategy was adopted to achieve chain lengthening with appropriate incorporation of functionality. The sensitive aldehyde 2 was further homologated to β-keto ester 17 in a model reaction sequence performed to simulate its ultimate projected coupling to 3.
- Paquette, Leo A.,Boulet, Serge L.
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p. 888 - 894
(2007/10/03)
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- Synthesis of Microcolin B, a Potent New Immunosuppressant Using an Efficient Mixed Imide Formation Reaction
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Microcolin B, a potent new immunosuppressant isolated from blue-green alga Lyngbya majuscula off the Venezuelan coast, has been made using a methyl-directed asymmetric hydrogenation reaction with rhodium on alumina catalyst on lactone 4 for the synthesis of the key (R,R)-2,4-dimethyl-octanoic acid fragment 1. A new, direct mixed imide formation reaction was also developed for the production of the unusual prolylpyrrolen-2-one 2 portion of microcolin. The pentafluorophenyl ester of CBZ-proline 5 was reacted with the lithium imidate of lactam 6, providing the mixed imide in 80% yield. Coupling of acid 1 with the N-terminus of the tripeptide, followed by coupling with pyrrolylproline 2, gave microcolin B. The new mixed-imide forming reaction was also applied to a formal total synthesis of microcolin A. The pentafluorophenyl ester of TBS-protected cis-hydroxyproline was coupled with lactam 6, and the resultant imide was converted to the key pyrrolylproline made previously for microcolin A.
- Andrus, Merritt B.,Li, Wenke,Keyes, Robert F.
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p. 5542 - 5549
(2007/10/03)
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- The First Stereoselective Palladium-Catalyzed Cyclocarbonylation of β,γ-Substituted Allylic Alcohols
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β,γ-Substituted allylic alcohols react with CO in the presence of catalytic quantities of palladium acetate and 1,4-bis(diphenylphosphino)butane affording α,β-substituted-γ-butyrolactones in 42-85% isolated yields. The complete stereoselectivity observed
- Brunner, Melanie,Alper, Howard
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p. 7565 - 7568
(2007/10/03)
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- Enzymes in Organic Synthesis, 19. The Enzyme-Catalyzed Sequential Esterification of (+/-)-anti-2,4-Dimethylglutaric Anhydride. - An Efficient Route to Enantiomerically Enriched Mono- and Diesters of anti-2,4-Dimethylglutaric Acid
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(+/-)-anti-2,4-Dimethylpentanedioic anhydride (rac-1) was converted in good yields and with high enantiomeric excess by an enzyme-catalyzed sequential esterification into the (2R,4R)-monoester 2 and the (2S,4S)-diester ent-3.Best results were obtained with Novozym 435, a lipase from Candida antarctica. - Key Words: Enzymes / Lipases / Pentanedioic anhydrides / Alcoholysis, enantioselective / Esterification, sequential
- Ozegowski, Ruediger,Kunath, Annamarie,Schick, Hans
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p. 215 - 218
(2007/10/02)
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- Synthesis of (-)-Probetaenone I: Structural Confirmation of Biosynthetic Precursor of Betaenone B
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(-)-Probetaenone I (1) has been synthesized by an intramolecular Diels-Alder reaction and, thereby, its structure has been clearly confirmed; in the biosynthesis of betaenone B (2) the stereochemistry of the C-8 hydroxylation of (1) was proved to involve retention of configuration.
- Miki, Shokyo,Sato, Yoshihiro,Tabuchi, Hiroyasu,Oikawa, Hideaki,Ichihara, Akitami,Sakamura, Sadao
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p. 1228 - 1229
(2007/10/02)
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- Enantiotopic-group Differentation. Catalytic Asymmetric Ring-opening of Prochiral Cyclic Acid Anhydrides with Methanol, using Cinchona Alkaloids
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Asymmetric ring-opening of prochiral acid anhydrides (1) with methanol has been achieved by a catalytic quantity of cinchona alkaloids (2).The product, the optically active half-ester (3), has been subjected to functional-group-selective reduction to give the optically active lactones (5).The reaction rate of the ring-opening and the extent of selectivity are dependent on the nature of the reaction medium, the polarity of solvent, and substrate concentration.By selecting the reaction conditions, an enantiometric excess of up to 70percent has been obtained.The kinetic isotope effect and other mechanistic investigations suggest that the reaction proceeds via general-base catalysis by the quinuclidine moiety of the base (2), and that the relative configuration of the C-9 hydroxy group with respect to the C-8 quinuclidine amino function determines the selectivity of the reaction.
- Hiratake, Jun,Inagaki, Minoru,Yamamoto, Yukio,Oda, Jun'ichi
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p. 1053 - 1058
(2007/10/02)
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- Macrocyclic Pyrrolizidine Alkakoid Analogues. Synthesis and Stereochemistry of (12R,14S)-and (12S,14R)-12,14-Dimethyl-1,2-didehydrocrotalanine. X-Ray Molecular Structure of the (12S,14R)-Isomer
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Treatment of (+)-retronecine (1) with meso-2,4-dimethylglutaric anhydride followed by lactonisation via the pyridine-2-thiol esters yielded (12R,14S)-(3) and (12S,14R)-dimethyl-1,2-didehydrocrotalanine (4).These pyrrolizidine alkaloid analogues were separated by column chromatography.The absolute configuration of the acid portion of each analogue was established by a seguence of two chemoselective reactions to afford optically active tetrahydro-3,5-dimethyl-2H-pyran-2-one.An X-ray crystal structure analysis confirmed the structure and stereochemistry of the (12S,14R)-isomer (4).The ester carbonyl groups of compound (4) are synparallel and directed below the plane of the macrocyclic ring.
- Brown, Kenneth,Burton, Michael,Robins, David J.,Sim, George A.
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p. 1261 - 1266
(2007/10/02)
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- An Asymmetric Synthesis of Lactones from Cyclic Acid Anhydrides with Chiral Binaphthyldiamines
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Asymmetric ring opening of the cyclic acid anhydrides cis-2,3-6 with the axially dissymmetric binaphthyldiamines (S)-1a-d and subsequent esterification gave diastereomeric mixtures of the amide-esters 7a-h.Successive reduction of the ester group and ring closure by hydrolysis afforded (-)-cis-2,4-dimethyl-δ-valerolactone (8, 92percent e.e.), (-)-mevalonolactone (9, 58percent e.e.)(+)-3-isopropyl-δ-valerolactone (10, 42percent e.e.), and (+)-2,3-methylene-γ-butyrolactone (11, 46percent e.e).Through kinetic resolution of the racemic anhydride trans-2, (-)-trans-2,4-dimethyl-δ-valerolactone (12) was yielded in a 74percent e.e., whose absolute configuration was established to be 2R,4R.
- Kawakami, Yukio,Hiratake, Jun,Yamamoto, Yukio,Oda, Jun'ichi
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p. 693 - 698
(2007/10/02)
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- SYNTHESIS OF BOTH THE ENANTIOMERS OF LARDOLURE, THE AGGREGATION PHEROMONE OF THE ACARID MITE, LARDOGLYPHUS KONOI
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Both the enantiomers of lardolure were synthesized in 100 percent optical purity and 99.6 percent diastereomeric purity by use of Frater's diastereoselective alkylation as the key-step.Since (1R,3R,5R,7R)-enantiomer showed the same ORD sign and bioactivity as those shown by the natural pheromone, the structure of lardolure was established unambiguously as (1R,3R,5R,7R)-1,3,5,7-tetramethyldecyl formate.
- Mori, Kenji,Kuwahara, Shigefumi
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p. 5539 - 5544
(2007/10/02)
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- Catalytic Asymmetric Induction from Prochiral Cyclic Acid Anhydrides using Cinchona Alkaloids
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Asymmetric ring-opening of prochiral cyclic acid anhydrides (1) with methanol was effected by a catalytic amount of cinchona alkaloids (2) with an enantiomeric excess of up to 70percent and the product was converted into optically active lactones.
- Hiratake, Jun,Yamamoto, Yukio,Oda, Jun'ichi
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p. 1717 - 1719
(2007/10/02)
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- ENZYMES IN ORGANIC SYNTHESIS-29. PREPARATIONS OF ENANTIOMERICALLY PURE cis-2,3- AND 2,4-DIMETHYL LACTONES VIA HORSE LIVER ALCOHOL DEHYDROGENASE-CATALYZED OXIDATIONS
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Further examples of the broad applicability of horse liver alcohol dehydrogenase-catalyzed oxidations of meso-diols as a route to chiral lactones of asymmetric synthetic value are described.The acyclic meso substrates, cis-2,3-dimethyl- and -diethylbutane-1,4-diols, and cis-2,4-dimethylpentane-1,5-diol, are stereospecifically oxidized in good yields to the corresponding enantiomerically pure γ- and δ-lactones.The oxidation of cis-3,4-bis(hydroxymethyl)thiacyclopentane is similarly stereospecific.For each meso-diol the oxidation takes place with a net stereospecifity for the hydroxymethyl groups attached to the S-centers, with the initially formed hydroxyaldehydes undergoing further enzyme-catalyzed oxidations via their hemiacetal forms to produce lactone products directly.
- Ng, George S. Y.,Yuan, Lung-Chi,Jakovac, Ignac J.,Jones, J. Bryan
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p. 1235 - 1244
(2007/10/02)
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- An Asymmetric Synthesis of 2,4-Dimethylvalerolactone and Mevalonolactone using Chiral Binaphthyldiamine Derivatives
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Axially dissymmetric binaphthyldiamine derivatives formed by asymmetric ring opening of the cyclic anhydrides (3) and (4) ring close on hydrolysis to give (-)-cis-2,4-dimethylvalerolactone (6) and (-)-mevalonolactone (7) in 92percent and 58percent enantiomeric excess (e.e.), respectively; similarly the derivative of the racemic cyclic anhydride (+/-)-(3) ring closes to give (-)-trans-2,4-dimethylvalerolactone with 74percent e.e.
- Kawakami, Yukio,Hiratake, Jun,Yamamoto, Yukio,Oda, Jun'ichi
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p. 779 - 781
(2007/10/02)
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- Stereoselective Synthesis of Alcohols, XI. Double Stereodifferentiation in the Addition of Crotylboronates to Aldehydes: Prelog-Djerassi Lactone
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Addition of the (Z)-crotylboronate 11 to (S)-(+)-α-methylbutyraldehyde (4) resulted in the Cram and Anti-Cram diastereomers 6 and 7.Their ratio depended on the chirality of the boronate component.Hence the formation of the alcohol 7 could be favoured by double stereodifferentiation.Similarly, on addition of the (E)-crotylboronate 12 predominant formation of the isomer 13 could be achieved.These observations formed the basis for a stereoselective synthesis of the Prelog-Djerassi lactone 3.
- Hoffmann, Reinhard W.,Zeiss, Hans-Joachim,Ladner, Wolfgang,Tabche, Susanne
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p. 2357 - 2370
(2007/10/02)
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