- Preparation of novel substituted haloarene compounds
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This invention relates to a new process for the preparation of novel substituted haloarene compounds of the formula I or IV: respectively, wherein R1, R2, R3, R4, R5, X, and Y are as defined herein, that comprises a novel and efficient selective mono-lithiation of a dihaloarene of the formula II or V: respectively, by an organo-lithium compound in the presence of a carbonyl reactant of the formula III: wherein R1 and R2 are as defined herein. In the process of the instant invention, the newly formed lithiated haloarene is sequentially quenched in situ by the carbonyl reactant to form said substituted haloarene. The process is suitable for batch or continuous flow systems. The substituted haloarenes produced by the process of the present invention are useful intermediates in the preparation of N-aryl or N-heteroaryl substituted pharmaceutically active compounds that include selective antagonists, inverse agonists and partial agonists of serotonin 1 (5-HT1) receptors useful in treating or preventing depression, anxiety, obsessive compulsive disorder (OCD) and other disorders for which a 5-HT1 agonist or antagonist is indicated.
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Page/Page column 6
(2008/06/13)
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- Direct Transformation of Trialkyl Phosphates into Organolithium Compounds by a DTBB-Catalysed Lithiation
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The reaction of different alkylic or phenylic phosphates 1 with an excess of lithium powder and a catalytic amount of DTBB (5 mol percent) in the presence of an electrophile -Barbier-type reaction conditions- in THF at -30 deg C leads to the formation of the expected products 2, resulting from the reaction of the in situ generated organolithium compound with the corresponding electrophile.
- Guijarro, David,Mancheno, Balbino,Yus, Miguel
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p. 8551 - 8558
(2007/10/02)
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- Direct transformation of dialkyl sulfates into alkyllithium reagents by a naphthalene-catalysed lithiation
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The lithiation of primary and secondary dialkyl sufates with an excess of lithium powder in the presence of a catalytic amount of naphthalene (4 mol %) in THF at -78°C leads to the corresponding alkyllithium reagents (1:2 molar ratio) which react with different electrophiles, mainly carbonyl compounds, to yield after hydrolysis, the expected coupling products. This methodology represents an indirect way to transform alcohols into organolithium compounds through the corresponding dialkyl sulfates. When the same procedure is applied to five or six member cyclic sulfates (derived from 1,2- or 1,3-diols) only products arising from a β- or γ-elimination process (giving olefins or cyclopropanes), respectively, are obtained.
- Guijarro, David,Guillena, Gabricia,Mancheno, Balbino,Yus, Miguel
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p. 3427 - 3436
(2007/10/02)
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- Synthesis of α-Hydroxy Ketones by Direct, Low-Temperature, in Situ Nucleophilic Acylation of Aldehydes and Ketones by Acyllithium Reagents
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The reaction of n-, sec-, and tert-butyllithium with CO at atmospheric pressure at -110 and -135 deg C in the appropriate solvent system in the presence of ketones and aldehydes generates the acyllithium, RC(O)Li, which reacts with the carbonyl compound to give the α-hydroxy ketone, generally in good yield.Reactions with aldehydes are limited in scope, working well with the t-BuLi-derived acyllithium reagents, but not with n-BuC(O)Li.
- Seyferth, Dietmar,Weinstein, Robert M.,Hui, Richard C.,Wang, Wei-Liang,Archer, Colin M.
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p. 5620 - 5629
(2007/10/02)
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- Stereochemical Aspects in the Insertion by Alkylidenemethylene Carbenoids into the α-C-H Bond of Alkoxides
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Primary alkoxides (R1CH2OM; M=K or Li) when treated with haloalkenes (R3R4C=CXY; X=Cl or Br, Y=H or Cl) in the presence of n-BuLi in THF at 0 deg C gave allylic alcohols (R1CH(OH)CH=CR3R4) through the insertion reaction of the corresponding alkylidenemethylene carbenoid () into the α-C-H bond of alkoxides.Secondary alkoxides (R1R2CHOM), under similar reaction conditions, gave butyl adducts (R1R2C(OH)C4H9) in addition to the insertion products.In particular, the C-H insertion of menthyl oxide proceeded without stereospecificity to give a mixture of the axial and equatorial insertion products.These results provided evidence for the hydride abstraction-recombination mechanism in the carbenoid insertion reaction.The regioselective, nonstereospecific insertion reaction was also observed when alkoxides were treated with separately prepared ((2,3-benzo-2-cyclohexylidene)chloromethyl)lithium at temperatures from -95 to -40 deg C.The absence of H-D scrambling in crossover experiments under these reaction conditions clearly showed that the hydride abstraction-recombination mechanism proceeded within a solvent cage.An inversion of configuration on the carbenoid carbon in the hydride abstraction step was proposed on the basis of the E/Z stereoselectivity in the insertion products.
- Oku, Akira,Harada, Toshiro,Hattori, Kazuhiro,Nozaki, Yohko,Yamaura, Yasunari
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p. 3089 - 3098
(2007/10/02)
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- ALDEHYDSELEKTIVITAET VON ALKYLHAFNIUM-KOMPLEXEN IN ALDEHYD-KETONKONKURRENZVERSUCHEN; VERGLEICH ZU ZIRKONIUM- UND TITAN-ANALOGEN KOMPLEXEN SOWIE THEORETISCHE DEUTUNG
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Cl3Hf-Me, in contrast to MeLi is not able to attack an ester or a nitrile group and fails to discriminate in competition experiments between heptanal and diethylketone.To the contrary, Cl3Hf-Bu and (EtO)3Hf-Me are highly aldehyde-selective.An explanation of these findings in comparison with alkylzirconium and alkyltitanium complexes is given.
- Kauffmann, Thomas,Pahde, Claudia,Wingbermuehle, Dorothea
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p. 4059 - 4062
(2007/10/02)
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- UEBER DIE ALDEHYDSELEKTIVITAET VON ALKYLKOMPLEXEN VON SCANDIUM, YTTRIUM, LANTHAN UND LANTHANIDEN IN ALDEHYD/KETON-KONKURRENZVERSUCHEN
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In-situ prepared alkyl complexes Hal2M-Alk (Alk = Me, Bu) of the f-metals Ce, Pr, Nd, Sm, Gd exhibit very low selectivity in competition experiments between heptanal and diethylketone in THF, whereas the selectivity of complexes Hal2M-Me (M = Sc, Y, La) is distinctly higher with decreasing tendency in the sequence Sc>Y>La.These and previously reported results led to a general working hypothesis about the reasons of the aldehyde-selectivity of transition metal alkyls.
- Kauffmann, Thomas,Pahde, Claudia,Tannert, Annegret,Wingbermuehle, Dorothea
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p. 4063 - 4066
(2007/10/02)
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- High-Yield Acyl Anion Trapping Reactions: Syntheses of α-Hydroxy Ketones and 1,2-Diketones
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The in situ generation of n-C4H9C(O)Li by the reaction of n-C4H9Li with CO at -110 deg C in the presence of ketones gives good (50-90percent) yields of α-hydroxy ketones.When the n-C4H9C(O)Li reaction is carried out in the presence of esters, good (65-80percent) yields of α-diketones are obtained, thus demonstrating that RC(O)Li can be reagents of practical utility.Similar reactions were observed with sec-C4H9Li and tert-C4H9Li.
- Seyferth, Dietmar,Weinstein, Robert M.,Wang, Wei-Liang
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p. 1144 - 1146
(2007/10/02)
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- ALDEHYDSPEZIFISCHE UND ALDEHYDSELEKTIVE ALKYLIERUNGEN MIT ORGANONIOB- UND -TANTAL-REAGENZIEN (1)
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In competition experiments with n-heptanal and diethylketone as substrates the reagents (CH3)2M(OiPr)3, CH3-MCl4 (M = Nb, Ta), and n-Bu-NbCl4 react exclusively or very selectively with the aldehyde.
- Kauffmann, Thomas,Antfang, Elmar,Ennen, Beate,Klas, Norbert
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p. 2301 - 2304
(2007/10/02)
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