- Stereochemical Versatility in Synthesis of Substituted Cycloalkanes from Acyclic Unsaturated Sugars
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Acyclic unsaturated sugars obtained by Wittig extension of aldehydo arabinose precursors undergo stereoselective Diels-Alder addition of cyclopentadiene, permitting isolation of a single, crystalline, optically pure norbornene adduct whose stereochemistry may be controlled by the enantiomeric form of the sugar used and the conditions of the cycloaddition reaction.
- Horton, Derek,Machinami, Tomoya,Takagi, Yasushi,Bergmann, Carl W.,Christoph, Gary C.
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- Enantioselective Construction of Modular and Asymmetric Baskets
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The precise positioning of functional groups about the inner space of abiotic hosts is a challenging task and of interest for developing more effective receptors and catalysts akin to those found in nature. To address it, we herein report a synthetic methodology for preparing basket-like cavitands comprised of three different aromatics as side arms with orthogonal esters at the rim for further functionalization. First, enantioenriched A (borochloronorbornene), B (iodobromonorbornene), and C (boronorbornene) building blocks were obtained by stereoselective syntheses. Second, consecutive A-to-B and then AB-to-C Suzuki–Miyaura (SM) couplings were optimized to give enantioenriched ABC cavitand as the principal product. The robust synthetic protocol allowed us to prepare (a) an enantioenriched basket with three benzene sides and each holding either tBu, Et, or Me esters, (b) both enantiomers of a so-called “spiral staircase” basket with benzene, naphthalene, and anthracene groups surrounding the inner space, and (c) a photo-responsive basket bearing one anthracene and two benzene arms.
- Badji?, Jovica D.,Finnegan, Tyler J.,Gunther, Michael J.,Pavlovi?, Radoslav Z.,Wang, Xiuze
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supporting information
p. 25075 - 25081
(2021/10/25)
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- Stereo- A nd regioselective synthesis of molecular baskets
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We describe a stereoselective method for obtaining multigram quantities of molecular basket 1syn in overall 11% yield, using inexpensive cyclopentadiene and diethyl fumarate as starting materials. First, an asymmetric synthesis of enantioenriched bromo(trimethylstannyl)alkene (-)-8 was accomplished by the stereoselective bromination of dibromonorbornene (+)-4 guided by anchimeric assistance and subsequent syn-exo-elimination of tetrabromonorbornane (-)-5a as the key steps. Subsequent Cu(I)-catalyzed cyclotrimerization of (-)-8 was optimized to give 1syn/anti in 85% yield and 1:1 ratio of diastereomers. Importantly, the results of our mechanistic experiments were in line with the cyclotrimerization occurring in a chain-type fashion with racemization of a Cu(I) homochiral dimeric intermediate, reducing the stereoselectivity of the transformation. Enabled by more facile access to molecular baskets of type 1syn, a range of recognition studies can now be completed for producing novel supramolecular catalysts, organophosphorus scavengers, and nanostructured materials.
- Gunther, Michael J.,Pavlovi?, Radoslav Z.,Fernandez, Joseph P.,Zhiquan, Lei,Gallucci, Judith,Hadad, Christopher M.,Badji?, Jovica D.
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p. 4392 - 4401
(2019/04/03)
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- A simple method for resolution of endo-/exo-monoesters of trans-norborn-5-ene-2,3-dicarboxylic acids into their enantiomers
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Separation of optical isomers obtainable from trans-norborn-5-ene-2,3-dicarboxylic acid methyl and tert-butyl monoesters was performed by crystallization of the respective salts prepared with (R)- and (S)-1-phenylethylamine. Starting from racemic endo-monomethyl ester of trans-norborn-5-ene-2,3-dicarboxylic acid, prepared by partial hydrolysis of the cyclopentadiene-dimethyl fumarate adduct, the corresponding (2R, 3R)-endo-monoester was isolated in 97% enantiomeric excess (ee) yield after seven repeated crystallizations from tetrachloromethane. Starting from exo-mono-tert-butyl ester of the same acid, prepared by alcoholysis of the cyclopentadiene-maleic anhydride adduct followed by isomerization, (2R, 3R)-exo-monoester was isolated in >98% ee yield after four repeated crystallizations from ethanol. Crystallization of the acids from the mother liquor yielded products with inverse stereochemical configuration.
- Kovalenko, Vitaly N.,Kozyrkov, Yurii Yu.
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p. 151 - 155
(2015/03/04)
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- Bioisostere of valtrate, anti-HIV principle by inhibition for nuclear export of Rev
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Rational design by the MO calculation disclosed 5,6-dihydrovaltrate (2) as the bioisostere of valtrate (1), the Rev-export inhibitor with anti-HIV activity. The synthesis of 2 was accomplished by ingenious use of asymmetric Diels-Alder reaction and stereoselective epoxidation associated with the adjacent hydroxyl group. Because of similar biological potency to 1, the analog 2 should be recognized as a promising scaffold for new anti-HIV agents with an unprecedented mechanism of action, inhibition for nuclear export of Rev protein, in the conventional remedy.
- Tamura, Satoru,Shimizu, Nobuhiro,Fujiwara, Katsuaki,Kaneko, Masafumi,Kimura, Tominori,Murakami, Nobutoshi
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scheme or table
p. 2159 - 2162
(2010/07/05)
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- [4 + 2] Cycloaddition reactions catalyzed by a chiral oxazaborolidinium cation. Reaction rates and diastereo-, regio-, and enantioselectivity depend on whether both bonds are formed simultaneously
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chemical equation presented The reaction rates and products in enantioselective Diels-Alder reactions with a range of dienophiles correlate with the expected degree of concertedness of bond formation in the transition state.
- Mukherjee, Santanu,Corey
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supporting information; experimental part
p. 1024 - 1027
(2010/06/15)
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- Di-2,2,2-trifluoro-1-(9-anthryl)ethyl fumarate, an easy starting point for the enantioselective preparation of trans-cyclohexene-4,5-dicarboxylate derivatives by Diels-Alder reaction
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Di-2,2,2-trifluoro-1-(9-anthryl)ethyl fumarate has been synthesized from fumaric acid and enantiopure Pirkle alcohol. The Diels-Alder reaction with different dienes employing different reaction conditions was assayed, with high diastereomeric excesses obtained. The structure and geometry of the cycloadducts was analyzed by NMR, molecular mechanics and X-ray diffraction. Hydrolysis made it possible to obtain the enantioenriched trans-cyclohexene-4,5-dicarboxylate derivatives and allow us to recover chiral auxiliary.
- Palomino-Schaetzlein, Martina,Virgili, Albert,Jaime, Carlos,Molins, Elies
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p. 3237 - 3243
(2007/10/03)
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- Influence of solvent polarity on the stereoselectivity of the uncatalyzed [4 + 2] cycloaddition of cyclopentadiene to an N,N′-fumaroyl bis-(six-membered ring [(2R)-10a-homobornane-10a,2-sultam])
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A new six-membered ring (2R)-bomane-10a,2-sultam was tested as chiral auxiliary for the [4 + 2] cycloaddition of cyclopentadiene to the bis-fumaroyl derivative (-)-lf and shows under chelating conditions similar complete selectivity to Oppolzer's sultam. Inversion of the π-face selectivity is nevertheless observed under uncatalyzed conditions under the influence of solvent polarity, varying from 82% de for the (2R,3R) cycloadduct 2f in trifluoroethanol to 70% de in favour of the (2S,3S) diastereoisomer in hexane as solvent. A predictive linear correlation is observed between the stereoselectivity and the solvent parameters according to the Abboud-Abraham-Kamlet-Taft model. PM3 calculations allowed a rationalization of these results based on the transition-state dipole moment. Illustrated by an x-ray analysis of cycloadduct (2S,3S)-2f, the main structural differences and influences in terms of steric and stereoelectronic factors are discussed by comparison of the five- versus six-membered ring homologues. Copyright
- Piatek, Anna,Chapuis, Christian,Jurczak, Janusz
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p. 700 - 708
(2007/10/03)
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- Stereoselectivity in the cycloaddition of cyclopentadiene to N-fumaroyl-[2R,S(R)]-bornane-10,2-sulfinamide monomethyl ester
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The cyclic [2R,S(R)]-bornane-10,2-sulfinamide (-)-2b, an analogue of Oppolzer's camphor-derived sultam (-)-2a, was synthesized by reduction of the known N-alkylidenesulfinamide (+)-1b with NaBH4. The uncatalyzed [4 + 2] cycloaddition of cyclopentadiene to the methyl ester (-)-3b of the N-fumaroylsulfinamide, obtained from (-)-2b, proceeds with lower endo and π-facial selectivity as compared to dienophiles (-)-3a, c. In contrast to these latter, the diastereoselectivity is reversed either in apolar CCl4 or in the presence of TiCl4. This inversion is explained by a competitive C(α)-si addition on the reactive anti-s-trans conformer.
- Chapuis, Christian,Kawecki, Robert,Urbanczyk-Lipkowska, Zofia
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p. 579 - 588
(2007/10/03)
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- Asymmetric Diels-Alder reaction of unsymmetrical maleates. A chemical access to chiral, unsymmetrical cis-cyclohexene-1,2-dicarboxylates
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A new route to optically active, unsymmetrical cis-cyclohexene-1,2-dicarboxylate derivatives has been developed on the basis of the asymmetric Diels-Alder reaction of chiral, unsymmetrical maleates catalyzed by certain Lewis acids. A notably high level of asymmetric induction has been observed in the asymmetric Diels-Alder reaction of unsymmetrical maleates possessing chiral auxiliaries such as α-phenethyl and trans-2-phenylcyclohexyl groups. The origin of the chiral outcome using these dienophiles has been elucidated.
- Maruoka, Keiji,Akakura, Matsujiro,Saito, Susumu,Ooi, Takashi,Yamamoto, Hisashi
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p. 6153 - 6158
(2007/10/02)
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- Preparation and Structural Analysis of Several New α,α,α',α'-Tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOL's) and TADDOL Analogs, Their Evaluation as Titanium Ligands in the Enantioselective Addition of Methyltitanium and Diethylzinc Reagents to Benzaldehyde, and Refinement of ...
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Preparation and screening of twenty new ligands, all analogs of α,α,α',α'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL), for the Ti-catalyzed asymmetric addition of methyltri(isopropoxy)titanium and diethylzinc to benzaldehyde are described.These ligands have the dioxolane ring of the TADDOL's replaced by cyclobutane, cyclopentane, cyclohexene, cyclohexane, bicycloheptene and -heptane and bicyclooctene and -octane moieties; several have H-atoms or alkyl groups in place of the aryl groups, and nine of them have C2 symmetry.X-Ray crystallography and molecular mechanics are used to analyze the structure of the ligands, and two structural features appear to correlate with selectivity: i) the torsion angle for the chelating O-atom and the ortho-C-atom of the axial Ph group (a small, ca. 19 deg, angle is optimum, Fig. 8) and ii) the "degree of perpendicularity" of the axial Ph group (Fig. 9).Competition experiments indicate that TADDOL 1a catalyzes both the methyltitanium and diethylzinc additions >/= 50 times faster than the related dioxolane analogs 12a, 12c, and 12e (Scheme 7), indicating that both axial and equatorial aryl groups (see Footnote 6) are necessary for ligand-accelerated catalysis of these reactions.A refined mechanistic hypotesis is presented (Fig. 10) to explain the selectivities observed for these new ligands.Our analysis suggests that a combination of structural features appear necessary for good catalytic efficiency and high selectivity.These features, especially the rather subtle conformational effects, appear to be optimized (among the ligands tested) in the TADDOL's.
- Ito, Yoshio N.,Ariza, Xavier,Beck, Albert K.,Bohac, Andrej,Ganter, Camille,et al.
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p. 2071 - 2110
(2007/10/02)
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- THERMAL AND CATALYTIC DIELS-ALDER REACTIONS BETWEEN (2E)-4,5,6-TRI-O-ACETYL-2,3-DIDEOXY-ALDEHYDO-D-ERYTHRO-HEX-2-ENOSE AND CYCLOPENTADIENE
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Thermal and catalytic reactions between (2E)-4,5,6-tri-2,3-dideoxy-aldehydo-D-erythro-hex-2-enose (1) and cyclopentadiene 1ed, in each case, to the four stereoisomeric 5-formyl-6-(1,2,3-tri-O-acetyl-D-erythro-triol-1-yl)bicyclohept-2-enes (2-5).The role of the catalysts is discussed, and the face selectivity is rationalized in terms of both steric and electrostatic arguments.Upon subsequent sodium borohydride reduction, iodination, and zinc reduction, the adducts 2-5 were converted to their respective primary alcohols 6-9, that could be separated by column chromatography.Sequential basic deacetylation, oxidative cleavage of the sugar side-chain with sodium metaperiodate, and reduction with sodium borohydride, yielded the previously known (5R,6R)- or(5S,6S)-bis(hydroxymethyl)norbornene-diols 12 or 13, thus establishing the C-5 and C-6 absolute configurations of their synthetic precursors.
- Serrano, Jose A.,Garcia, Eulalia G.,Roman, Emilio
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p. 1121 - 1134
(2007/10/02)
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- Conformational Diagnosis of Diethyl (4S,5S)-4,5-Bis(tert-butyldimethylsiloxy)-2E,6E-octadienedioate Based on the Stereochemical Outcomes of Representative Reactions As Compared with Those of Its 4,5-O-Isopropylidene Derivatives and on a Dichroic Exciton C
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In order to gain more insight into the conformation of diethyl (4S,5S)-4,5-bis(tert-butyldimethylsiloxy)-2E,6E-octadienedioate (1) experimentally, some appropriate reactions of 1 and its derivative (S,S)-3, which bears isopropylidene protecting groups, ha
- Saito, Seiki,Narahara, Osamu,Ishikawa, Teruhiko,Asahara, Masahiro,Moriwake, Toshio,et al.
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p. 6292 - 6302
(2007/10/02)
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- Stereocontrol in Diels-Alder cycloaddition to unsaturated sugars: Reactivities of acyclic seven-carbon trans dienophiles derived from aldopentoses
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Acyclic trans-2,3-unsaturated aldoheptonate derivatives (1-9) obtained from D-aldopentoses by Wittig chain-extension served as dienophiles for a detailed comparative study of their asymmetric Diels-Alder cycloaddition with cyclopentadiene. Cycloaddition under uncatalyzed thermal conditions gave mixtures of the four possible stereoisomeric norbornene adducts. The endo:exo ratios and the diastereofacial selectivities in the formation of the adducts were determined by NMR spectroscopy and by chemical transformations. The quantitative distribution of adducts as a function of stereochemistry of the dienophile is discussed. Acyclic trans-2,3-unsaturated aldoheptonate derivatives (1-9) obtained from D-aldopentoses by Wittig chain-extension served as dienophiles for a detailed comparative study of their asymmetric Diels-Alder cycloaddition with cyclopentadiene. Cycloaddition under uncatalyzed thermal conditions gave mixtures of the four possible stereoisomeric norbornene adducts. The endo:exo ratios and the diastereofacial selectivities in the formation of the adducts were determined by NMR spectroscopy and by chemical transformations. The quantitative distribution of adducts as a function of stereochemistry of the dienophile is discussed.
- Horton,Koh
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p. 249 - 260
(2007/10/02)
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- Enzymatic resolution of norbor(NE)nylmethanols in organic media and an application to the synthesis of (+)- and (-)-endo-norbornene lactone
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The enzymatic resolution of some norbornene carboxylic acids, norbornenylmethanols and -methylamines was evaluated. The kinetic resolution of norbornyl- and norbornenylmethanols by Porcine Pancreatic Lipase (PPL)-catalyzed transesterification in methyl acetate as the solvent leads to corresponding acetates and remaining methanols both of high enantiomeric purity. A useful application is the synthesis of both enantiomers of endo-norbornene lactone 8n via transesterification of iodolactone 18. The influence of structural variations on the efficiency of the PPL-catalyzed resolution of lactone methanols 21, 23, 25 and 28, at the optimal reaction conditions established for iodolactone 18, was investigated.
- Janssen,Klunder,Zwanenburg
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p. 5513 - 5538
(2007/10/02)
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- Enzymatic Preparation of Optically Active Bicycloheptene Derivatives, Building Blocks of Terpenoid Natural Products. An Attractive Alternative to Enantioselective Diels-Alder Syntheses
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Bicycloheptene derivatives (1)-(3), building blocks of terpenoid natural products, have been prepared with high enantiometric purities by enzymatic hydrolysis of their racemic esters in the presence of porcine liver esterase (PLE) and an ester hydrolase from Pseudomonas sp. (SAM-II).
- Eycken, J. Van der,Vandewalle, M.,Heinemann, G.,Laumen, K.,Schneider M. P.,et al.
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p. 306 - 308
(2007/10/02)
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- A Convenient Synthesis of Both Enantiomeric 2,3-Disubstituted 5-Norbornenes from D-Mannitol
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A convenient synthesis of both enantiomeric trans- and cis-2,3-disubstituted 5-norbornenes (bicycloheptenes), 2 and 3, has been developed by utilizing the Diels-Alder reaction between cyclopentadiene and chiral dienophiles obtained from a single chiral template D-mannitol (1).
- Takano, Seiichi,Kurotaki, Ayako,Ogasawara, Kunio
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p. 1075 - 1078
(2007/10/02)
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- CHIRAL SYNTHESIS OF ASYMMETRICALLY TETRA-SUBSTITUTED CYCLOPENTANE DERIVATIVES BY DIELS-ALDER ADDITION OF CYCLOPENTADIENE TO UNSATURATED ACYCLIC-SUGAR DERIVATIVES
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Optically pure, substituted cyclopentane derivatives of interest in synthesis of prostaglandin analogs have been obtained by stereocontrolled addition of cyclopentadiene to trans α,β-unsaturated sugar derivatives.Methyl (E)-4,5,6,7-tetra-O-acetyl-2,3-dide
- Horton, Derek,Machinami, Tomoya,Takagi, Yasushi
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p. 135 - 162
(2007/10/02)
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- Synthesis of Asymmetrically-substituted Cyclopentane Derivatives from Acyclic Sugars
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Diels-Alder addition of cyclopentadiene and trans-α,β-unsaturated sugar derivatives proceeds with high steric control to afford crystalline, optically pure norbornene derivatives that may be transformed into tetra-C-substituted cyclopentane derivatives of defined stereochemistry at all four centres; the products are of interest in synthesis of prostaglandin analogues.
- Horton, Derek,Machinami, Tomoya
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