- Novel nitrile oxide cycloaddition approach towards papuamine: Stereoselective synthesis of a potentially useful trans-hydrindane intermediate
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In a potentially useful approach to the marine alkaloid papuamine 1, a known trans-hydrindane intermediate 17 has been synthesised in racemic form using a model sequence of reactions involving a nitrile oxide cycloaddition as a key step.
- Saha, Arabinda,Bhattacharjya, Anup
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- Epimerization of Tertiary Carbon Centers via Reversible Radical Cleavage of Unactivated C(sp3)-H Bonds
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Reversible cleavage of C(sp3)-H bonds can enable racemization or epimerization, offering a valuable tool to edit the stereochemistry of organic compounds. While epimerization reactions operating via cleavage of acidic C(sp3)-H bonds, such as the Cα-H of carbonyl compounds, have been widely used in organic synthesis and enzyme-catalyzed biosynthesis, epimerization of tertiary carbons bearing a nonacidic C(sp3)-H bond is much more challenging with few practical methods available. Herein, we report the first synthetically useful protocol for the epimerization of tertiary carbons via reversible radical cleavage of unactivated C(sp3)-H bonds with hypervalent iodine reagent benziodoxole azide and H2O under mild conditions. These reactions exhibit excellent reactivity and selectivity for unactivated 3° C-H bonds of various cycloalkanes and offer a powerful strategy for editing the stereochemical configurations of carbon scaffolds intractable to conventional methods. Mechanistic study suggests that the unique ability of N3? to serve as a catalytic H atom shuttle is critical to reversibly break and reform 3° C-H bonds with high efficiency and selectivity.
- Wang, Yaxin,Hu, Xiafei,Morales-Rivera, Cristian A.,Li, Guo-Xing,Huang, Xin,He, Gang,Liu, Peng,Chen, Gong
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supporting information
p. 9678 - 9684
(2018/07/21)
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- Carbonylation of ethylenically unsaturated compounds
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A process for the carbonylation of ethylenically unsaturated compounds including vinyl esters and a process for the production of 3-hydroxy propanoate esters or acids. The process comprises reacting said compound with carbon monoxide in the presence of a source of hydroxyl groups and of a catalyst system. The catalyst system is obtainable by combining: (a) a metal of Group 8, 9 or 10 or a compound thereof: and (b) a bidentate ligand of general formula (I): X1(X2)-Q2-A-R—B-Q1-X3(X4).
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Page/Page column 37
(2016/06/01)
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- CARBONYLATION OF ETHYLENICALLY UNSATURATED COMPOUNDS
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PROBLEM TO BE SOLVED: To provide a process for the carbonylation of ethylenically unsaturated compounds including vinyl esters and a process for the production of 3-hydroxypropanoate esters or 3-hydroxypropanoic acids. SOLUTION: The process comprises reacting the compound with carbon monoxide in the presence of a source of hydroxyl groups and of a catalyst system. The catalyst system is obtainable by combining: (a) a metal of Group 8, 9 or 10 or a compound thereof: and (b) a bidentate ligand of general formula (I): X1(X2)-Q2-A-R-B-Q1-X3(X4). COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0205
(2016/10/09)
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- Discovery of octahydroindenes as PAR1 antagonists
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Octahydroindene was identified as a novel scaffold for protease activated receptor 1 (PAR1) antagonists. Herein, the 2-position (C2) was explored for structure-activity relationship (SAR) studies. Compounds 14, 19, and 23b showed IC50 values of 1.3, 8.6, and 2.7 nM in a PAR1 radioligand binding assay, respectively, and their inhibitory activities on platelet activation were comparable to that of vorapaxar in a platelet rich plasma (PRP) aggregation assay. This series of compounds showed high potency and no significant cytotoxicity; however, the compounds were metabolically unstable in both human and rat liver microsomes. Current research efforts are focused on optimizing the compounds to improve metabolic stability and physicochemical properties as well as potency.
- Lee, Sunkyung,Song, Jong-Hwan,Park, Chul Min,Kim, Jin-Seok,Jeong, Ji-Hye,Cho, Woo-Young,Lim, Dong-Chul
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supporting information
p. 1054 - 1058
(2013/12/04)
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- [6+5] FUSED BICYCLES AS A THROMBIN ANTAGONIST, PROCESS FOR PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE BICYCLES
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The present invention relates to the new [6+5] fused bicycle derivatives, pharmaceutically acceptable salts or isomers thereof, processes for preparing the same, and pharmaceutical compositions comprising the same. The [6+5] fused bicycle derivatives can antagonize the thrombin receptor and thus may be effectively used for the treatment and prevention of thrombus, platelet aggregation, atherosclerosis, restenosis, blood coagulation, hypertension, arrhythmia, angina pectoris, heart failure, inflammation and cancer when used alone or with other cardiovascular agents.
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Page/Page column 42
(2012/01/14)
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- A mechanistic study on the intramolecular ionic Diels-Alder reaction of 2-methyl-3,9,11-tridecatriene-2-ol and 2,11-dimethyl-1,3,9,11-dodecatetraene
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Intramolecular ionic Diels-Alder reaction of 2-methyl-3,9,11-tridecatriene-2-ol (1) was studied under acidic conditions. Treatment of 2-methyl-3,9,11-tridecatriene-2-ol (1) with trifluoromethanesulfonic acid yielded 7-methyl-8-isopropenyl-1,2,3,4,4aR
- Ko, Yoon-Joo,Shim, Seung-Bo,Shin, Jung-Hyu
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p. 863 - 867
(2007/10/03)
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- Characterization and alkane oxidation activity of a diastereopure seven-coordinate iron(III) alkylperoxo complex
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Spectroscopic characterization and alkane oxidation studies of a diastereopure seven-coordinate high-spin iron(iii) alkylperoxo complex based on the chiral N,N′,N-bis(l-prolinate)pyridine ligand Py(ProMe)2 (1) are reported. The Royal Society of Chemistry 2007.
- Gosiewska, Silvia,Permentier, Hjalmar P.,Bruins, Andries P.,Van Koten, Gerard,Gebbink, Robertus J. M. Klein
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p. 3365 - 3368
(2008/02/10)
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- Synthesis of α,β-unsaturated dioxanes, dioxolanes and dioxepanes by trans-acetalisation of dimethylacetals with meso or C 2-symmetrical 1,2-, 1,3- and 1,4-diols
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Several o-dibenzylic diols were prepared reacting organometallics with o-phthalaldehyde at room temperature in ether. The identity of the meso and C2-symmetrical (D,L) isomers as well as their ratio were determined by chiral gas chromatography. The meso and C2 (racemic) stereoisomeric diols were easily separated by flash chromatography on silica gel. A set of 18 α,β-unsaturated acetals were then prepared reacting those, as well as commercially available 1,2, 1,3 and 1,4 diols, with the corresponding methylacetals in acidic medium. A trans-acetalisation procedure adapted to the cases of fragile allylic alcohols or unfavorable 1,6 diols-derived dioxonanes based on a Dean-Stark trapping of methanol was also employed.
- Lemiègre, Lo?c,Lesetre, Fleur,Combret, Jean-Claude,Maddaluno, Jacques
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p. 415 - 427
(2007/10/03)
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- Hydrolysis of cyclic orthoesters: Experimental observations and theoretical rationalization
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Reaction products using labelled water (H2O18) and the relative rate of hydrolysis of the four bicyclic orthoesters 1-4 having a six or a seven-membered orthoester ring are reported. With the help of theoretical calculations (semi-empirical AM1 and ab initio 3-21G level), the results are explained by taking into account proton affinities as well as steric and stereoelectronic effects.
- Li, Shigui,Dory, Yves L.,Deslongchamps, Pierre
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p. 14841 - 14854
(2007/10/03)
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- Total synthesis of Taxol. 2. Construction of A and C ring intermediates and initial attempts to construct the ABC ring system
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A method for the formation of Taxol's ABC ring system has been developed. General methods for the synthesis of versatile synthons for Taxol's A ring (8) and C ring (55) are presented. A model study using a simplified C ring synthon (17) confirmed the viability of the sequential Shapiro-McMurry strategy for formation of Taxol's B ring. Careful exploration of the chemistry of various A-B ring conjugates allowed the development of a successful method for formation of the B ring in a more functionalized system.
- Nicolaou,Liu,Yang,Ueno,Sorensen,Claiborne,Guy,Hwang,Nakada,Nantermet
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p. 634 - 644
(2007/10/02)
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- Stereoselectivity in intramolecular diene cyclozirconation: A combined experimental and theoretical approach
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Intramolecular diene cyclozirconation (1 → 2 + 3 → 4) can be highly diastereoselective (97:3 trans/cis for 4). It is suggested that the cis and trans diastereomers of the zirconacycle are equilibrating under the conditions of the reaction, and that the observed diastereomeric preference of 4 reflects the relative stability of the two diastereomeric zirconacycles. Results for the intramolecular cyclozirconation of two other dienes, 8 and 14, as well as for the "heterodiene" N,N-diallylaniline are also reported. Computational results at the molecular mechanics, semiempirical molecular orbital ZINDO and nonlocal density functional theory levels are used to explain the observed stereochemistry in terms of thermodynamic and kinetic control.
- Taber, Douglass F.,Louey, James P.,Wang, Yanong,Nugent, William A.,Dixon, David A.,Harlow, Richard L.
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p. 9457 - 9463
(2007/10/02)
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- Enzyme-catalysed esterification of (±)-trans-cyclohexane-1,2-dimethanol
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The (S),(S)-diesters (8), (10) and (12) have been obtained from the diol (±)-(6) in Lipozyme-catalysed esterification reactions.
- Roberts,Steukers,Taylor
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p. 969 - 972
(2007/10/02)
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- Deazetation of a Bicyclic Azo Compound: Resolution of a Stereochemical Ambiguity and Conformational Analysis of a Biradical
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Development of a new approach has permitted a fuller analysis of the stereochemistry of deazetation of the stereospecifically deuteriated azo compound (1d) than could be achieved previously, in that it has proved possible to analyse 2H2>octa-1,7-diene for E,E-, E,Z,-and Z,Z-content.This has given results for the thermal and photochemical reactions that can be rationalised in terms of partial conformational equilibration of the biradical.
- Samuel, Christopher J.
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p. 1259 - 1265
(2007/10/02)
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- Enzymes in Organic Synthesis. 24. Preparations of Enantiomerically Pure Chiral Lactones via Stereospecific Horse Liver Alcohol Dehydrogenase Catalyzed Oxidations of Monocyclic Meso Diols
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Preparative-scale horse liver alcohol dehydrogenase catalyzed oxidation of monocyclic meso diols provides a direct and convenient one-step route to a broad range of chiral γ-lactones of value as synthons in asymmetric synthesis.The general applicability of the method is demonstrated by oxidations of cis-1,2-bis(hydroxymethyl) substrates of the cyclohexyl, cyclohexenyl, cyclopentyl, cyclobutyl, cyclopropyl, and dimethylcyclopropyl series.For each diol, oxidation of the hydroxymethyl group attached to the S chiral center occurs exclusively, and the pure γ-lactone products are isolated in high (68-90percent) yields and of 100percent ee.In contrast, the enzyme does not exhibit significant enantiomeric selectivity in its catalysis of oxidations of the corresponding racemic trans diols.The stereospecificities observed, or lack thereof, are as predicted by the active-site model.
- Jakovac, Ignac J.,Goodbrand, H. Bruce,Lok, Kar P.,Jones, J. Bryan
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p. 4659 - 4665
(2007/10/02)
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- Conformational Equilibrium in 8-Methyl-cis-2-thiahydrindane and 8-Methyl-cis-2-oxahydrindane by 13C NMR Spectroscopy
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The preferred conformation of 8-methyl-cis-thiahydrindane has been both estimated by 13C NMR chemical shifts and determined by low temperature 13C NMR spectroscopy to be the conformer with the methyl group equatorial with respect to the cyclohexane ring.This result is in disagreement with the interpretation of the temperature dependence of the CD spectra of (+) and (-) 8-methyl-cis-2-thiahydrindane, whereby the conformation with the methyl group axial with respect to the cyclohexane ring was claimed to be the preferred conformation.The preferred conformation of the related oxygen heterocycle, 8-methyl-cis-2-oxahydrindane, has been estimated by 13C NMR chemical shifts to be the conformer with the methyl group axial with respect to the cyclohexane ring.Possible reasons for these observations are discussed.
- Willer, Rodney L.
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p. 261 - 265
(2007/10/02)
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- SILICIUMORGANISCHE VERBINDUNGEN. LXXIII. HYDRIERTE 2,4-DIOXA-SILEPINE, -SILOCINE UND -SILONINE
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Silylation of the diols I-V with hexamethylcyclotrisilazane (VI) leads to the 3,3-dimethyl derivatives of hydrogenated 2,4-dioxa-cis- (VII) and -trans-benzo-(VIII), -cyclohexene- (IX), -cyclohexadieno- (X) and -naphtho-3-silepines (XI).The diols XVIII and
- Birkofer, Leonhard,Gruener, Wolfgang,Stuhl, Oskar
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p. 159 - 166
(2007/10/02)
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- Struktur eines O,N-Ketenacetals: (1RS,8SR,10SR)4(15)Z)-4-Aethyliden-5-oxa-3-azatricyclo3,8>tetradecan)
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Methods for the preparation of a series of model compounds which were required for stereochemical studies are described: the tricyclic O,N-ketenacetal 1, the two diastereomeric bicyclic amino acids 7 and 10 (see Scheme 2), and the two diastereomeric conformationally fixed tetrahydro-1,3-oxazines (=1,3-oxazines) 9 and 11.An x-ray analysis of racemic 1 reveals a quasi-tetrahedral nitrogen pyramid of the O,N-ketene acetal grouping, and an almost perfect conformational analogy between the N- and C-centered allylic positions at the double bond.
- Kuemin, Albin,Maverick, Emily,Seiler, Paul,Vanier, Noel,Damm, Lorenz,et al.
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p. 1158 - 1175
(2007/10/02)
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