- Total synthesis of (R,R,R)-α-tocopherol through asymmetric cu-catalyzed 1,4-addition
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By introducing a disposable activating substituent at C-3, the asymmetric 1,4-addition to a notoriously unreactive 2-substituted chromenone was achieved with high levels of (2R)-stereoselectivity in the presence of a chiral CuI-phosphoramidite
- Termath, Andreas Ole,Sebode, Hanna,Schlundt, Waldemar,Stemmler, René T.,Netscher, Thomas,Bonrath, Werner,Schmalz, Hans-Günther
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- Chiroptical properties of organic radical cations. The electronic and vibrational circular dichroism spectra of α-tocopherol derivatives and sterically hindered chiral hydroquinone ethers
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Qualitatively and quantitatively reliable electronic and vibrational circular dichroism (ECD and VCD) spectra of chiral organic radical cations were obtained for the first time with α-tocopherol derivatives and sterically hindered chiral hydroquinone ethers. The isolation and spectral measurements of chiral radical cation salts were made possible by using nitrosonium or antimony derivatives as electron-transfer oxidants, which can cleanly oxidize the substrate donors without giving any byproducts in the sample solution. Such reliable ECD spectra enabled us to fully examine the chiroptical properties of organic radical cations and also compare them with those of the corresponding neutral compounds. The observed VCD spectra of neutral and radical cationic species of chiral hydroquinone ether were nicely simulated by density functional theory (DFT) calculations, from which the relative contribution of each radical cation conformer in solution was evaluated. Thus, the combined synthetic, spectroscopic, and theoretical protocol, composed of chiral modification, clean oxidation to form stable radical cations, ECD/VCD spectral analyses, and DFT calculations, was demonstrated to be a powerful, indispensable tool for elucidating a comprehensive picture of radical cationic species in solution.
- Mori, Tadashi,Izumi, Hiroshi,Inoue, Yoshihisa
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- Total Synthesis of α-Tocopherol through Enantioselective Iridium-Catalyzed Fragmentation of a Spiro-Cyclobutanol Intermediate
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A conceptionally new strategy for the asymmetric (2R-selective) synthesis of α-tocopherol (vitamin E) was developed. In the stereocontrolled key step, a prochiral spiro[chromane-2,3′-cyclobutanol] unit is effectively desymmetrized under C?C bond activation in an unprecedented iridium-catalyzed transformation using (S)-DTBM-SegPhos as a chiral ligand (e.r. 97:3). To complete the synthesis, the side chain was attached through Ru-catalyzed cross-metathesis employing an alkene derived from (R,R)-hexahydrofarnesol. To suppress epimerization during the final hydrogenation, PtO2 had to be used as a catalyst instead of Pd/C. In an alternative approach (employing a propargyl-substituted spiro-cyclobutanol), the side chain was constructed prior to the Ir-catalyzed ring fragmentation (>99:1 d.r.) through enyne cross-metathesis (using an alkene derived from (R)-dihydrocitronellal) followed by Cr-catalyzed 1,4-hydrogenation and (diastereoselective) Pfaltz hydrogenation of the resulting triple-substituted olefin. The work demonstrates the potential of iridium catalysis for enantioselective C?C bond activation.
- Ratsch, Friederike,Schlundt, Waldemar,Albat, Dominik,Zimmer, Anne,Neud?rfl, J?rg-Martin,Netscher, Thomas,Schmalz, Hans-Günther
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p. 4941 - 4945
(2019/03/21)
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- Synthesis of 2,2-dialkyl chromanes by intramolecular Ullmann C–O coupling reactions toward the total synthesis of D-α-tocopherol
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The complete synthesis of D-α-tocopherol was achieved using our developed-Ullmann C–O coupling reaction as a key reaction. The synthesis of the core structure of D-α-tocopherol, which is a chiral chromane, has never been reported using intramolecular Ullmann C–O coupling reactions owing to the low reactivity of electron-rich iodoarenes with tertiary alcohols. Because the developed intramolecular C–O coupling reactions prefer electron-rich iodoarenes with tertiary alcohols, we successfully synthesized the chiral chromane core and achieved the total synthesis of D-α-tocopherol.
- Tsubogo, Tetsu,Aoyama, Saki,Takeda, Rika,Uchiro, Hiromi
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p. 843 - 846
(2018/09/10)
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- SYNTHESIS OF CHROMANE COMPOUNDS AND THEIR DERIVATIVES BY A COPPER-CATALYZED CONJUGATE ADDITION REACTION
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The present invention relates to the preparation of chromane compounds and their derivatives by a copper-catalyzed conjugate addition reaction. It has been observed that in highly stereoselective manner a methyl group can be introduced to the 2 position o
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- Synthesis of chromane compounds and their derivatives by a copper-catalyzed conjugate addition reaction
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The present invention relates to the preparation of chromane compounds and their derivatives by a copper-catalyzed conjugate addition reaction. It has been observed that in highly stereoselective manner a methyl group can be introduced to the 2 position o
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- Iridium-catalyzed asymmetric hydrogenation of unfunctionalized, trialkyl-substituted olefins
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Chiral iridium complexes with bicyclic pyridine-based N,P ligands have emerged as efficient catalysts for the enantioselective hydrogenation of unfunctionalized trialkyl-substituted olefins. Optimization of the reaction conditions by variation of the solvent, pressure, and temperature led to enantiomeric excesses of up to 99%. Three pure alkenes, (E)-2-cyclohexyl-2- butene and (E)- and (Z)-3,4-dimethyl-2-pentene were converted into the corresponding chiral alkanes with 97%, 94%, and 93% ee, respectively. Hydrogenation of the three C=C bonds of both α- and γ-tocotrienyl acetate led to α- and γ-tocopheryl acetate with very high diastereoselectivity. The same catalysts were successfully applied in the hydrogenation of trisubstituted alkenes with a carboxylic ester or a keto group in the γ position. This reaction was used as a key step in a highly enantioselective synthesis of the pheromone of the caddisfly Hesperophylax occidentalis. The hydrogenation of a structurally analogous allylic alcohol also gave high enantioselectivities. Unfunctionalized trialkyl-substituted olefins are hydrogenated with high efficiency and excellent enantioselectivity using iridium complexes derived from chiral N,P ligands. In this way, pharmaceutically interesting and industrially relevant compounds with chiral alkyl fragments are easily accessible with high diastereo- and enantioselectivities. Copyright
- Wang, Aie,Fraga, Rui P. A.,Hoermann, Esther,Pfaltz, Andreas
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p. 599 - 606
(2011/10/12)
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- Asymmetric synthesis of α-Tocopherol
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α-Tocopherol was synthesized from a chiral intermediate α-hydroxy ester by means of two ring-closing methods to yield the chromanol in 94 % diastereomeric excess.
- Hengartner, Urs,Chougnet, Antoinette,Liu, Kegang,Woggon, Wolf-D.
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experimental part
p. 1306 - 1311
(2010/06/12)
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- Biomimetic chromanol cyclisation: A common route to a-tocotrienol and α-tocopherol
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A common synthetic route to a-tocotrienol and a-tocopherol has been accomplished by a biomimetic cyclisation that yields the chromanol ring. The chirality at C2 of the chro- manol was induced by a covalently attached chiral dipeptide. Its terminal Asp participates in the enantioface-selective pro-tonation of the double bond of the a-tocotrienol precursor. a-Tocotrienol was diastereoselectively hydrogenated to a-tocopherol.
- Chapelat, Julien,Chougnet, Antoinette,Woggon, Wolf-D.
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experimental part
p. 2069 - 2076
(2009/09/08)
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- Determination of the stereoisomers of racemic α-tocopherol in pharmaceutical preparations by high-performance liquid chromatography and gas chromatography
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In the present study we used chiral high performance liquid chromatography and gas chromatography to determine the stereoisomers of racemic α-tocopherol. The Chiralcel OD-H and Silar-100 AT columns were used. Statistical evaluation of the results established the precision of these methods.
- Klaczkow, Gabriela,Anuszewska, Elzbieta L.
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experimental part
p. 715 - 721
(2009/07/25)
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- Diastereoselective synthesis of α-tocopherol: A new concept for the formation of chromanols
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(Chemical Equation Presented) A diastereoselective synthesis of α-tocopherol 1 (93% de) was achieved via two key steps, (i) a highly diastereoselective Shi epoxidation of a trisubstituted alkene and (ii) an acid supported, "anti-Baldwin" epoxide ring opening under inversion of configuration leading to the 6-membered chromanol ring.
- Chapelat, Julien,Buss, Axel,Chougnet, Antoinette,Woggon, Wolf-D.
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supporting information; experimental part
p. 5123 - 5126
(2009/05/30)
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- A short route to α-tocopherol
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(Chemical Equation Presented) Short and sweet: A simple and practical route to α-tocopherol is described (see scheme; TES=triethylsilyl). The key step is a remarkably diastereoselective domino aldol/oxa-Michael reaction, which is promoted by proline derivative 1.
- Liu, Kegang,Chougnet, Antoinette,Woggon, Wolf-D.
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supporting information; experimental part
p. 5827 - 5829
(2009/03/11)
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