- Concurrent Formation of N-H Imines and Carbonyl Compounds by Ruthenium-Catalyzed C-C Bond Cleavage of β-Hydroxy Azides
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A commercial cyclopentadienylrutenium dicarbonyl dimer ([CpRu(CO)2]2) efficiently catalyzes the formation of N-H imines and carbonyl compounds simultaneously from β-hydroxy azides via C-C bond cleavage under visible light. Density functional theory calculations for the cleavage reaction support the mechanism involving chelation of alkoxy azide species and liberation of nitrogen as the driving force. The synthetic utility of the reaction was demonstrated by a new amine synthesis promoted by chemoselective allylation of imine and synthesis of isoquinoline.
- Lee, Jeong Min,Bae, Dae Young,Park, Jin Yong,Jo, Hwi Yul,Lee, Eunsung,Rhee, Young Ho,Park, Jaiwook
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supporting information
p. 4608 - 4613
(2020/06/05)
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- Oxidative β-Halogenation of Alcohols: A Concise and Diastereoselective Approach to Halohydrins
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β-Halohydrins bearing transformable halo- and hydroxyl groups, are easily converted into various valuable blocks in organic and pharmaceutical synthesis. A diastereoselective β-halogenation of benzylic alcohols was achieved under simple and low-cost conditions, which provided a direct synthesis of β-halohydrins. The simple reaction conditions, easily available reagents, high diastereoselectivities, and additional oxidant-free make this reaction very attractive and practical.
- Ai, Lingsheng,Wang, Weijin,Wei, Jialiang,Li, Qing,Song, Song,Jiao, Ning
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supporting information
p. 437 - 441
(2019/02/26)
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- Bromination of olefins with HBr and DMSO
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A simple and inexpensive methodology is reported for the conversion of alkenes to 1,2-dibromo alkanes via oxidative bromination using HBr paired with dimethyl sulfoxide, which serves as the oxidant as well as cosolvent. The substrate scope includes 21 olefins brominated in good to excellent yields. Three of six styrene derivatives yielded bromohydrins under the reaction conditions.
- Karki, Megha,Magolan, Jakob
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p. 3701 - 3707
(2015/04/22)
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- From simple organobromides or olefins to highly value-added bromohydrins: A versatile performance of dimethyl sulfoxide
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A novel and efficient direct transformation of secondary bromides or olefins to highly value-added bromohydrins has been disclosed. Dimethyl sulfoxide (DMSO), a cheap and common solvent, performs its versatile role as a solvent, an essential oxidant, and also as an oxygen source in this bromohydrin synthesis.
- Song, Song,Huang, Xiaoqiang,Liang, Yu-Feng,Tang, Conghui,Li, Xinwei,Jiao, Ning
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supporting information
p. 2727 - 2731
(2015/05/27)
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- Discovery of a novel class of dimeric smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582)
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A series of dimeric compounds based on the AVPI motif of Smac were designed and prepared as antagonists of the inhibitor of apoptosis proteins (IAPs). Optimization of cellular potency, physical properties, and pharmacokinetic parameters led to the identification of compound 14 (AZD5582), which binds potently to the BIR3 domains of cIAP1, cIAP2, and XIAP (IC50 = 15, 21, and 15 nM, respectively). This compound causes cIAP1 degradation and induces apoptosis in the MDA-MB-231 breast cancer cell line at subnanomolar concentrations in vitro. When administered intravenously to MDA-MB-231 xenograft-bearing mice, 14 results in cIAP1 degradation and caspase-3 cleavage within tumor cells and causes substantial tumor regressions following two weekly doses of 3.0 mg/kg. Antiproliferative effects are observed with 14 in only a small subset of the over 200 cancer cell lines examined, consistent with other published IAP inhibitors. As a result of its in vitro and in vivo profile, 14 was nominated as a candidate for clinical development.
- Hennessy, Edward J.,Adam, Ammar,Aquila, Brian M.,Castriotta, Lillian M.,Cook, Donald,Hattersley, Maureen,Hird, Alexander W.,Huntington, Christopher,Kamhi, Victor M.,Laing, Naomi M.,Li, Danyang,MacIntyre, Terry,Omer, Charles A.,Oza, Vibha,Patterson, Troy,Repik, Galina,Rooney, Michael T.,Saeh, Jamal C.,Sha, Li,Vasbinder, Melissa M.,Wang, Haiyun,Whitston, David
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p. 9897 - 9919
(2014/01/17)
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- Asymmetric synthesis of chiral 1,3-diaminopropanols: Bisoxazolidine- catalyzed C-C bond formation with α-keto amides
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Three high-yielding steps lead to the formation of chiral 1,3-diaminopropanols from aliphatic and aromatic α-keto amides. In this approach, a nitroaldol reaction, which is catalyzed by Cu(SO2CF 3)2 and the bisoxazolidine ligand L1, is followed by two mild reduction reactions (see scheme). Laborious protection and deprotection steps can be avoided by using this method.
- Xu, Hanhui,Wolf, Christian
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supporting information; experimental part
p. 12249 - 12252
(2012/02/01)
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- Highly regio- and diastereoselective halohydroxylation of olefins: A facile synthesis of vicinal halohydrins
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An efficient method for the synthesis of vicinal chlorohydrin or bromohydrin derivatives has been developed on the basis of direct halohydroxylation of various olefins with electrondonating or withdrawing substituent. The reactions were carried out under mild conditions in the presence of N-tosyl-l-threonine (NTsLT) as an acidic additive using chloramine T trihydrate, 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) or N-bromoacetamide (AcNHBr) as the halogen source, respectively, affording the corresponding vicinal halohydrins in good to high yields with excellent regio- and stereoselectivities.
- Zhang, Jinglei,Wang, Jie,Qiu, Zhuibai,Wang, Yang
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experimental part
p. 6859 - 6867
(2011/10/02)
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- Organocatalysis in the stereoselective bromohydrin reaction of alkenes
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An efficient regio- and stereo-selective (>99:1) trans-bromohydrination (bromohydroxylation and bromomethoxylation) of alkenes including α,β-unsaturated carbonyl compounds with N-bromosuccinimide (NBS) has been achieved by using 1.0 mol% of N,N'-diarylthi
- Bar, Sukanta
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experimental part
p. 605 - 612
(2010/08/21)
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- Et2Zn-mediated rearrangement of bromohydrins
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(Chemical Equation Presented) A simple and highly efficient method for the rearrangement of bromohydrins mediated by Et2Zn to synthesize carbonyl compounds was described. Various β-bromo alcohols were treated with 0.6 equiv of Et2Zn to form a zinc complex in CH 2Cl2 at room temperature for 2 h, followed by 1,2-migration to give the corresponding carbonyl compounds. This remarkable and clean rearrangement is general for acyclic and cyclic bromohydrins, and a variety of ring-expansive and -contractive carbonyl compounds were obtained in good to excellent yields according to the feature of the starting bromohydrins. The functional group tolerance of organozinc reagents in this reaction will be useful in organic synthesis. The scope and limitations of this rearrangement process were also investigated.
- Li, Lezhen,Cai, Peijie,Guo, Qingxiang,Xue, Song
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p. 3516 - 3522
(2008/09/20)
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- Piperazine compounds
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A compound selected from those of formula (I): wherein: R1, R2, R3 and R4, which may be the same or different, each represent an atom or group selected from hydrogen, halogen, alkyl, alkoxy, phenyl and cyano, X represents a bond, an oxygen atom or a group selected from —(CH2)m—, —OCH2— and —NR5—, wherein m represents 1 or 2, and R5 is as defined in the description, Y represents an oxygen atom or a group selected from NR7 and CHR8, wherein R7 and R8 are as defined in the description, Z represents a nitrogen atom or a CH group, n represents 1 or 2, Ak represents an alkylene chain, Ar represents an aryl or heteroaryl group, its optical isomers, and addition salts thereof with a pharmaceutically acceptable acid. Medical products containing the same which are useful in the treatment of conditions requiring a serotonin reuptake inhibitor and/or NK1 antagonist.
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Page/Page column 10-11
(2008/06/13)
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- Development of an efficient process for the preparation of Sch 39166: Aziridinium chemistry on scale
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A large-scale synthesis of a tricyclic D1/D5 dopamine antagonist based on regio- and stereoselective ring opening of an aziridinium ion with a Grignard reagent was optimized and scaled up.
- Gala, Dinesh,Dahanukar, Vilas H.,Eckert, Jeffery M.,Lucas, Brian S.,Schumacher, Doris P.,Zavialov, Ilia A.,Buholzer, Patrik,Kubisch, Peter,Mergelsberg, Ingrid,Scherer, Dominik
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p. 754 - 768
(2013/09/03)
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- Bromination of tetralin. Short and efficient synthesis of 1,4-dibromonaphthalene
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High-temperature bromination of tetralin (1,2,3,4-tetrahydronaphthalene) with bromine resulted in benzylic biomination to give 1,4-dibromo-1,2,3,4-tetrahydronaphthalene (4) as a major product and several secondary products. Photolytic bromination of tetralin and subsequent double dehydrobromination of 1,1,4,4-tetrabromo-1,2,3,4-tetrahydronaphthalene (10) gave 1,4-dibromonaphthalene (11) as the sole product in a high yield. 1,4-Dibromonaphthalene is efficiently converted to the corresponding methoxy (12 and 13) and cyano (14 and 15) derivatives of naphthalene.
- Cakmak, Osman,Kahveci, Ismail,Demirtas, Ibrahim,Hoekelek, Tuncer,Smith, Keith
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p. 1791 - 1804
(2007/10/03)
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- Novel stereoselective syntheses of the fused benzazepine dopamine D1 antagonist (6as,13br)-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5h-benzo[d]naphth[2,1-b] azepin-12-ol (sch 39166): 1. aziridinium salt based syntheses
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Several novel enantioselective syntheses of the dopamine D1 antagonist (6aS,13bR)-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H-benzo[d]naphth[2,1-b] azepin-12-ol (2) are described in which the key intermediate was 1-(2,2-dimethoxyethyl)-1-methyl-1a,2,3,7b-tetrahydro-1H-naphth[1,2-b]aziridinium salt (20). The latter species was prepared either from 1-(2,2-dimethoxyethyl)-1a,2,3,7b-tetrahydro-1H-naphth[1,2-b]-azirine (18) by methylation or from the tertiary amino alcohols 1-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro-2-naphthalenol (23) or 2-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro-1-naphthalenol (24) by tosylation and in situ ring closure. Regioselective trapping of 20 with Grignard reagent (4-chloro-3-methoxyphenyl)magnesium bromide (10) then afforded the trans amine 1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-1,2,3,4-tetrahydro-N-methyl- 2-naphth-alenamine (22), which was cyclized to give 11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-12-methoxy-5H-benzo[d]-naphth[2,1-b] azepine (9), a known precursor of 2. Several enantioselective syntheses, including a Jacobsen epoxidation route, a de no novo synthesis from L-homophenylalanine, and a classical salt resolution sequence, were developed for the preparation of the key intermediates in chiral form.
- Draper, Richard W.,Hou, Donald
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p. 175 - 185
(2013/09/08)
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- Catalytic asymmetric synthesis of secondary alcohols using chiral cis-amino-2-hydroxy-1,2,3,4-tetrahydronaphthalene as chiral ligand
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The synthesis and resolution of cis-1-amino-2-hydroxy-1,2,3,4-tetrahydronaphthalene 5 by a simple and straightforward methodology has been achieved. The homochiral aminoalcohol has been used in the catalytic reduction of ketones by means of BH3 · SMe2 affording secondary alcohols in high enantiomeric excesses. On the contrary low enantiomeric excesses have been obtained when (1S,2R)-N,N-dibutyl-1-amino-2-hydroxytetrahydronaphthalene 11 has been used to catalyze the enantioselective addition of Et2Zn to benzaldehyde.
- Bellucci, Cristina M.,Bergamini, Antonio,Cozzi, Pier Giorgio,Papa, Angelo,Tagliavini, Emilio,Umani-Ronchi, Achille
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p. 895 - 902
(2007/10/03)
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