- Simple Synthesis of γ-Spirolactams by Birch Reduction of Benzoic Acids
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A convenient synthesis of γ-spirolactams in only two steps was developed. Birch reduction of benzoic acids and immediate alkylation with chloroacetonitrile afforded cyclohexadienes in high yields. The products could be isolated by crystallization on a large scale in analytically pure form. Subsequent hydrogenation with platinum(IV) oxide as the catalyst reduced the nitrile functionality and the double bonds in the same step with excellent stereoselectivity. The relative configurations were determined unequivocally by X-ray analyses. Direct cyclization of the intermediary formed amino acids afforded the desired γ-spirolactams in excellent overall yields. The procedure is characterized by few steps, cheap reagents, and can be performed on a large scale, interesting for industrial processes.
- Krüger, Tobias,Kelling, Alexandra,Schilde, Uwe,Linker, Torsten
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p. 1074 - 1077
(2017/02/23)
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- Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent
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Emerging work on organocatalytic enantioselective halocyclizations naturally draws on conditions where both new bonds must be formed under delicate control, the reaction regime where the concerted nature of the AdE3 mechanism is of greatest importance. Without assistance, many simple alkene substrates react slowly or not at all with conventional halenium donors under synthetically relevant reaction conditions. As demonstrated earlier by Shilov, Cambie, Williams, Fahey, and others, alkenes can undergo a concerted AdE3-type reaction via nucleophile participation, which sets the configuration of the newly created stereocenters at both ends in one step. Herein, we explore the modulation of alkene reactivity and halocyclization rates by nucleophile proximity and basicity, through detailed analyses of starting material spectroscopy, addition stereopreferences, isotope effects, and nucleophile-alkene interactions, all obtained in a context directly relevant to synthesis reaction conditions. The findings build on the prior work by highlighting the reactivity spectrum of halocyclizations from stepwise to concerted, and suggest strategies for design of new reactions. Alkene reactivity is seen to span the range from the often overgeneralized "sophomore textbook" image of stepwise electrophilic attack on the alkene and subsequent nucleophilic bond formation, to the nucleophile-assisted alkene activation (NAAA) cases where electron donation from the nucleophilic addition partner activates the alkene for electrophilic attack. By highlighting the factors that control reactivity across this range, this study suggests opportunities to explain and control stereo-, regio-, and organocatalytic chemistry in this important class of alkene additions.
- Ashtekar, Kumar Dilip,Vetticatt, Mathew,Yousefi, Roozbeh,Jackson, James E.,Borhan, Babak
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supporting information
p. 8114 - 8119
(2016/07/16)
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- Substituent effects on the dehydration of arene hydrates in aqueous solution
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Rate constants have been determined by UV spectrophotometry at 25 °C for the acid-catalyzed dehydration of different types of monocyclic arene hydrates including those substituted at the 1-, 2- or 3-positions. General acid catalysis was not observed, and linear plots of pseudo-first-order rate constants for dehydration against hydronium concentration were obtained. A Hammett plot of the second-order rate constants for acid-catalyzed dehydration, kH (M-1s-1), of unsubstituted- (8a), 3-substituted (8b, 8c, 8d, 8e) and 1-substituted-benzene hydrates (14f and 14h) shows an excellent correlation with σ+ values and yields a large negative ρ-value of -6.5. The results are consistent with rate-determining formation of a benzenium ion in which direct mesomeric interaction with the substituent occurs, presumably permitted by the coplanar arrangement of the diene and carbocation centre in the intermediate. Data points for 2-substituted arene hydrates (13f, 13g, 13h, 13i) deviate negatively from the Hammett plot as direct mesomeric interaction with the substituent is not possible in the corresponding benzenium intermediates. Copyright 2013 John Wiley & Sons, Ltd. A large negative ρ-value of -6.5 is obtained in a correlation of rate constants for the acid-catalyzed dehydration of arene hydrates with σ+ values. Copyright
- O'Mahony, Michelle J.,More O'Ferrall, Rory A.,Boyd, Derek R.,Lam, Casey M.,O'Donoghue, Annmarie C.
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supporting information
p. 989 - 996
(2014/01/06)
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- Enantioselective divergent approaches to both (-)-platensimycin and (-)-platencin
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Enantioselective divergent approaches to (-)-platencin and (-)-platensimycin have been developed. A rationally designed chiral synthetic intermediate, possessing a useful α,β-unsaturated sulfone functionality, which served as a masked ketone as well as a good Michael acceptor, was successfully prepared via the highly enantioselective catalytic asymmetric intramolecular cyclopropanation (CAIMCP) developed in our laboratory. Copyright
- Hirai, Sho,Nakada, Masahisa
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experimental part
p. 518 - 530
(2011/03/19)
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- An enantioselective approach to (-)-platencin via catalytic asymmetric intramolecular cyclopropanation
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This Letter describes an enantioselective approach to (-)-platencin. A uniquely functionalized chiral intermediate, which was prepared via the highly enantioselective catalytic asymmetric intramolecular cyclopropanation (CAIMCP) that we have developed, was successfully transformed to Nicolaou's intermediate in his total synthesis of (-)-platencin.
- Hirai, Sho,Nakada, Masahisa
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scheme or table
p. 5076 - 5079
(2011/01/04)
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- Hydroxide ion as electron source for photochemical Birch-type reduction and photodehalogenation
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The photochemical Birch-type reduction of arenes and the photodehalogenation of haloarenes by a hydroxide ion that acted as an electron source occurred in 2-PrOH. The efficiency of these photoreactions was dependent on the nature of the substrate, the concentration of NaOH, and the solvent used. These photoreactions provide an environmentally friendly method for the reduction of aromatic rings and dehalogenation.
- Yoshimi, Yasuharu,Ishise, Akihiro,Oda, Hiromu,Moriguchi, Yousuke,Kanezaki, Hiroki,Nakaya, Yukari,Katsuno, Kayoko,Itou, Tatsuya,Inagaki, Sho,Morita, Toshio,Hatanaka, Minoru
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p. 3400 - 3404
(2008/09/21)
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- Protonated benzene: A case for structural memory effects?
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Photoionization tandem-mass spectrometry of selectively deuterium labeled precursor molecules is used to probe the structure of protonated benzene which had been questioned in a provocative publication by Mason and co-workers (J. Chem. Soc., Chem. Commun. 1995, 1027). Specifically, we address the intriguing aspect of a postulated delayed hydrogen ring-walk by modulating the internal energy content of mass-selected C6H7-nDn + ions. To this end, ionization of selectively deuterated precursors by tunable synchrotron photons is combined with chemical monitoring of H +/D+ transfer from C6H7-nD n+ to a strong base B. The resulting BH +/BD+ ratios monotonically decrease with increasing internal energy content and, due to the virtue of the regioselective deuterium label incorporations, thereby disprove a delayed hydrogen ring-walk or any other "structural memory effect" in C6H7-nD n+ ions. As a consequence, the experimental studies of Mason et al. were reconsidered using sector-field mass spectrometry. These extensive studies suggest that the previous observations might have been obscured by a combination of isobaric impurities, metastable-ion contributions, and artifact signals.
- Schroeder, Detlef,Loos, Jessica,Schwarz, Helmut,Thissen, Roland,Dutuit, Odile
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p. 9931 - 9937
(2008/04/18)
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- Half-sandwich ruthenium (II) compounds comprising nitrogen containing ligands for treatment of cancer
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Compounds which may be used in the treatment and/or prevention of cancer have the formula (I) wherein: R1, R2, R3, R4, R5 and R6 independently represents H, alkyl, —CO2R′, aryl or akylaryl, which latter two groups are optionally substituted on the aromatic ring; R′ represent alkyl, aryl or alkaryl; X is halo, H2O, (R′)(R″)SO, R′CO2— or (R′)(R″)C═O, where R″ represents alkyl, aryl or alkaryl; Y is a counterion; m is 0 or 1; q is 1, 2 or 3; C′ is C1 to C12 alkylene, optionally substituted in or on the alkylene chain, bound to two A groups; p is 0 or 1 and r is 1 when p is 0 and r is 2 when p is 1; and A and B are: each independently N-donor nitrite ligands; or B is halo and A is an N-donor pyridine ligand, optionally substituted at one or more of the carbon atoms of the pyridine ring; or p is 0, A is NR7R8 and B is NR9R10, wherein R7, R8, R9 and R10 independently represent H or alkyl, and A and B are linked by an alkylene chain, optionally substituted in or on the alkylene chain, or p is 1, A is NR7 and B is NR9R10, wherein R7, R9 and R10 are as previously defined, and A and B are linked by an alkylene chain, optionally substituted.
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- Catalytic Asymmetric C-C Bond Formation: Asymmetric Synthesis of cis-Decalin Derivatives by Palladium-Catalyzed Cyclization of Prochiral Alkenyl Iodides
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A catalytic asymmetric synthesis by the use of a Heck-type reaction has been realized for the first time, giving the cis-decalin derivative 5 in up to 46percent ee.
- Sato, Yoshihiro,Sodeoka, Mikiko,Shibasaki, Masakatsu
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p. 4738 - 4739
(2007/10/02)
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- A Study of Gaseous Benzenium and Toluenium Ions generated from 1,4-Dihydro- and 1-Methyl-1,4-dihydro-benzoic Acids
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Gaseous benzenium C6H7(1+) (1) and toluenium C7H9(1+) (2) ions have been generated by mass spectrometric loss of .CO2H from the corresponding 1,4-dihydrobenzoic acids (3) and (4), and their fragmentations after ca. 10 μs have been investigated by means of mass-analysed ion kinetic energy (MIKE) spectrometry of some 2H and 13C labelled analogues.Metastable C6H7(1+) ions eliminate H2 after proton randomization, whereas metastable C7H9(1+) ions expel both H2 and CH4 after incomplete proton equilibration.In particular, 40percent of C7H9(1+) ions randomize all their carbon and hydrogen atoms prior to loss of CH4, and 60percent of C7H9(1+) ions lose the original methyl group along with a hydrogen atom from the (proton-equilibrated) benzenium ring, accompanied by a slow and incomplete exchange between the hydrogen atoms of the ring and the methyl group.It is suggested that loss of both CH4 and H2 occur via the (ipso-)toluenium ion (2).The role of a non-classical C7H9(1+) isomer, phenylmethonium ion (6), is discussed since striking similarities are found compared * adducts from ion-molecule reactions described in the literature.
- Kuck, Dietmar,Schneider, Jens,Gruetzmacher, Hans-Friedrich
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p. 689 - 696
(2007/10/02)
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- Regioselectivity of the Intermolecular Diels-Alder Reaction of Acyl Nitroso Compounds (C-Nitrosocarbonyl Compounds) and Nitrosoformates (O-Nitrosocarbonyl Compounds). Preparation of Functionalized cis-Δ6-1-Octalones
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A study of the regioselectivity of the intermolecular Diels-Alder reaction of (nitrosocarbonyl)benzene and methyl nitrosoformate with representative electron-rich and electron-deficient 2-substituted 1,3-cyclohexadienes is described.The observed results are consistent with the prediction that nitrosocarbonyl compounds behave as dependable electron-deficient 2? components in a normal (HOMOdiene controlled) Diels-Alder reaction with electron-rich 2-substituted dienes and additionally illustrate that they may serve as useful 2? components in regioselective Diels-Alder reactions with electron-deficient 2-substituted 1,3-cyclohexadienes.The latter results are consistent with either a normal (HOMOdiene controlled) or inverse electron demand (LUMOdiene controlled) Diels-Alder reaction.Utilization of the nitrosocarbonyl Diels-Alder adducts in a stereospecific preparation of functionalized, cis-Δ6-1-octalone is detailed.In contrast to predictions based on secondary orbital control (allylic axial heteroatom orbital control), cycloaddition of butadiene with the 5- and 6-substituted N-benzoyl 3-aza-2-oxobicyclooct-5-enes occurs on the face bearing the RCON-O bridge.
- Boger, Dale L.,Patel, Mona,Takusagawa, Fusao
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p. 1911 - 1916
(2007/10/02)
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- A HYBRID BIRCH-CLAISEN METHODOLOGY FOR ARYLATION AT ALLYLIC TERMINI: SYNTHESIS OF (+/-)-HERBERTENE
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A hybrid Birch-Claisen methodology has been developed for the regio- and stereo-controlled arylation of allyl groups, and applied to a synthesis of (+/-)-herbertene.
- Chandrasekaran, S.,Turner, John V.
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p. 3799 - 3802
(2007/10/02)
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- Transition Metal-Diene Complexes. Part 4. The Crystal and Molecular Structure and Isomerization of η-Cyclopentadienyl(η-3-methoxycarbonyl-cyclohexa-1,4-diene)rhodium(I)
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Crystals of the title compound, , are monoclinic, space group I2/a with cell dimensions a=28.124(14), b=6.141(8), c=14.569(11) Angstroem, β=112.43(9) deg, and Z=8.The intensities of 1 325 reflections above background were collected by counter methods and refined to R 0.052.The rhodium atom is bonded to the five carbon atoms of the planar cyclopentadienyl ring and to the four olefinic carbon atoms of the cyclohexa-1,4-diene.The cyclohexa-1,4-diene ring is in the boat conformation with the two saturated carbon atoms lying 0.66, 0.70 Angstroem above the plane of the four olefinic carbons in a direction away from the metal.The carbomethoxy-subtituent is planar and occupies an axial position with respect to the cyclohexadiene boat.The title complex undergoes a kinetically controlled isomerization when heated in toluene or acid-free o-dichlorobenzene to a mixture of complexes containing co-ordinated 5-methoxy-carbonyl- (major product) and 2-methoxycarbonyl-cyclohexa-1,3-diene (minor product).In the presence of acid in o-dichlorobenzene the major product undergoes a secondary isomerization to the complex containing co-ordinated 1-methoxycarbonylcyclohexa-1,3-diene.For the primary isomerization a mechanism involving the formation of a hydro-η3-allylic intermediate is proposed in which the rate-determining step is a carbon-to-metal hydride-ion transfer.For the secondary isomerization, in the presence of acid, a reverse metal-to-carbon hydrogen transfer is believed to operate.
- Drew, Michael G. B.,Regan, Catrionia M.,Nelson, S. Martin
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p. 1034 - 1040
(2007/10/02)
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- Orbital Interactions. VIII. Competition Kinetic Measurements of the Birch Reduction of Some Compounds Having the Bicycloheptadiene Framework as a Means of Investigating Orbital Interactions Through Space in These Systems
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Relative rate constants for the Birch reduction (Li liq.NH3/t-butyl alcohol) of norbornadiene (1), 1,4-dihydro-1,4-methanonaphthalene (3), 9-(1-Methylethylidene)-1,4-dihydro-1,4-methanonaphthalene (5), 1,4-dihydro-1,4-epoxynaphthalene (7), lithium benzoate, α-methylstyrene, and the hexahydrobenzenomethanoanthracene (20a), were obtained and compared with that obtained for the reduction of norbornene from an earlier study.Compounds (1), (3) and (5) were some 105 times more readily reduced than norbornene.These results are best explained in terms of the presence of trough-space interactions operating between the two lowest unoccupied molecular orbitals in these molecules.The Birch reduction of (7) gave mainly 1,4-dihydronaphthalene (17).A mechanism for this reaction is presented.
- Paddon-Row, Michael N.,Hartcher, Robert
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p. 785 - 794
(2007/10/02)
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