- Nickel-Catalyzed Multicomponent Coupling: Synthesis of α-Chiral Ketones by Reductive Hydrocarbonylation of Alkenes
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A nickel-catalyzed, multicomponent regio- and enantioselective coupling via sequential hydroformylation and carbonylation from readily available starting materials has been developed. This modular multicomponent hydrofunctionalization strategy enables the straightforward reductive hydrocarbonylation of a broad range of unactivated alkenes to produce a wide variety of unsymmetrical dialkyl ketones bearing a functionalized α-stereocenter, including enantioenriched chiral α-aryl ketones and α-amino ketones. It uses chiral bisoxazoline as a ligand, silane as a reductant, chloroformate as a safe CO source, and a racemic secondary benzyl chloride or an N-hydroxyphthalimide (NHP) ester of a protected α-amino acid as the alkylation reagent. The benign nature of this process renders this method suitable for late-stage functionalization of complex molecules.
- Chen, Jian,Zhu, Shaolin
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supporting information
p. 14089 - 14096
(2021/09/13)
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- NOVEL THYROMIMETICS
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Compounds are provided having the structure of Formula (I): or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein A, X1, X2, Q, R1, R2 and n are as defined herein. Such compounds function as thyromimetics and have utility for treating diseases such as neurodegenerative disorders and fibrotic diseases. Pharmaceutical compositions containing such compounds are also provided, as are methods of their use and preparation.
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Page/Page column 154
(2020/09/19)
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- Iron-catalysed enantioconvergent Suzuki-Miyaura cross-coupling to afford enantioenriched 1,1-diarylalkanes
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The first stereoconvergent Suzuki-Miyaura cross-coupling reaction was developed to afford enantioenriched 1,1-diarylalkanes. An iron-based complex containing a chiral cyanobis(oxazoline) ligand framework was best to obtain enantioenriched 1,1-diarylalkanes from cross-coupling reactions between unactivated aryl boronic esters and benzylic chlorides. Enhanced yields were obtained when 1,3,5-trimethoxybenzene was used as an additive, which is hypothesized to extend the lifetime of the iron-based catalyst. Exceptional enantioselectivities were obtained with challenging ortho-substituted benzylic chlorides. This journal is
- Tyrol, Chet C.,Yone, Nang S.,Gallin, Connor F.,Byers, Jeffery A.
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supporting information
p. 14661 - 14664
(2020/12/02)
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- IMIDAZO-PYRIDINE COMPOUNDS AS PAD INHIBITORS
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Heterocyclic compounds of Formula (I), (II), and (III) are described herein along with their polymorphs, stereoisomers, prodrugs, solvates, co-crystals, intermediates, pharmaceutically acceptable salts, and metabolites thereof. The compounds described herein, their polymorphs, stereoisomers, prodrugs, solvates, co-crystals, intermediates, pharmaceutically acceptable salts, and metabolites thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosis, cutaneous lupus erythematosis, ulcerative colitis, cancer, cystic fibrosis, asthma, multiple sclerosis and psoriasis. The process of preparation of the compounds of Formula (I), (II), and (III), their polymorphs, stereoisomers, prodrugs, solvates, co-crystals, intermediates, pharmaceutically acceptable salts, and metabolites thereof, along with a pharmaceutical composition comprising a compound of Formula (I), Formula (II), Formula (III), or a pharmaceutically acceptable salt thereof have also been described.
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Paragraph 000133; 000321
(2019/05/10)
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- Metal-free regioselective hydrochlorination of unactivated alkenes via a combined acid catalytic system
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A combined acid HCl/DMPU-acetic acid catalytic system was used in the hydrochlorination of a wide range of unactivated alkenes. This hydrochlorination strategy is remarkably greener than previous reported methods in terms of high atom efficiency, no toxic waste generated and metal-free process. The higher efficiency, compared with other commercially available HCl reagents, was augmented by the good regioselectivity and functionality tolerance found. A stepwise mechanism for this hydrochlorination process was proposed based on kinetic studies.
- Liang, Shengzong,Hammond, Gerald B.,Xu, Bo
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supporting information
p. 680 - 684
(2018/02/14)
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- Direct halogenation of alcohols with halosilanes under catalyst- and organic solvent-free reaction conditions
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A chemoselective method for the direct halogenation of different types of alcohols with halosilanes under catalyst- and solvent-free reaction conditions (SFRC) is reported. Various primary, secondary and tertiary benzyl alcohols and tertiary alkyl alcohols were directly transformed to the corresponding benzyl and alkyl halides, respectively, using chlorotrimethylsilane (TMSCl) and bromotrimethylsilane (TMSBr).
- Ajvazi, Njomza,Stavber, Stojan
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supporting information
p. 2430 - 2433
(2016/05/19)
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- Nickel-catalyzed asymmetric reductive cross-coupling between vinyl and benzyl electrophiles
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A Ni-catalyzed asymmetric reductive cross-coupling between vinyl bromides and benzyl chlorides has been developed. This method provides direct access to enantioenriched products bearing aryl-substituted tertiary allylic stereogenic centers from simple, stable starting materials. A broad substrate scope is achieved under mild reaction conditions that preclude the pregeneration of organometallic reagents and the regioselectivity issues commonly associated with asymmetric allylic arylation.
- Cherney, Alan H.,Reisman, Sarah E.
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supporting information
p. 14365 - 14368
(2014/12/11)
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- DMSO-catalyzed chlorination of alcohols using N-phenylbenzimidoyl chloride
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N-phenylbenzimidoyl chloride has been demonstrated as an efficient chlorination reagent catalyzed by dimethyl sulfoxide (DMSO) in conversion of alcohols to corresponding chlorides. The reaction conditions were mild, and most of the substrates gave satisfactory yields. The configuration inversion of the chlorination was proved using optically active phenyl alcohols. The amount of DMSO can be as low as 0.001 eq without reducing the efficiency of the chlorination. A plausible mechanism for the reaction was proposed and proved by experiments. The reaction is stereoselective and potentially chemoselective among primary benzyl alcohols, secondary benzyl alcohols, and unactivated aliphatic alcohols.
- Wang, Qiang,Xu, Jian,Xu, Zhou-Qing,Yan, Ji-Dan
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p. 2071 - 2076
(2013/06/05)
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- A highly chemoselective and rapid chlorination of benzyl alcohols under neutral conditions
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A rapid and highly selective chlorination method has been developed using 2,4,6-trichloro-1,3,5-triazine (TCT) catalyzed by dimethyl sulfoxide. The reactions take 10 to 40 minutes, and the yields are almost quantitative. The neutral reaction conditions are compatible with substrates bearing acid-labile functional groups. Both competitive intramolecular and intermolecular reactions for benzyl alcohols in the presence of aliphatic alcohols indicate high selectivity. The procedure has been successfully used in the selective chlorination of gastrodin, a clinically used neuromedicine. This procedure represents a useful new tool in organic and medicinal chemistry. Georg Thieme Verlag Stuttgart.
- Sun, Lili,Peng, Guisheng,Niu, Hongmei,Wang, Qiang,Li, Chunbao
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experimental part
p. 3919 - 3924
(2009/05/26)
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- Lipoxygenase inhibiting compounds
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Compounds of the formula: STR1 where R1 is amino or methyl; R2 is C1 -C2 alkyl; R3 is one or more substituents selected from hydrogen, halogen or trihalomethyl; R4 is one or more substituents selected from hydrogen, halogen, trihalomethyl, C1 to C4 alkoxy or C1 to C4 alkyl; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C1 to C6 alkoyl are inhibitors of 5- and/or 12-lipoxygenase enzymes.
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- Conformational Dependence of Isotope Effects for Hyperconjugating Methyl Groups. Nonadditivity of NMR Isotope Shifts in Benzylic Ions
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Deuterium substitution in the methyl groups induces long-range downfield shifts in 13C NMR signals of the ortho and para positions of the phenyldimethylcarbenium ion.Similar downfield isotope shifts occur in 19F signals of (p-fluorophenyl)carbenium ions upon deuteration of α-methyl groups.These NMR isotope shifts are analogous to secondary β-deuterium isotope effects on rates and equilibria and arise from hyperconjugative interactions.The effects of substituting entire CD3 groups for CH3 groups are additive, but the effects of deuterium substitution within a methyl group are not additive.The nonadditive behavior is attributed to unequal populations of the possible methyl conformation for partially deuterated methyl groups, so that each C-H(D) bond is not equally involved in hyperconjugation.This interpretation is supported by the observation of an isotope effect on the vicinal 1H-19F coupling constant in the phenylmethylfluorocarbenium ion, PhCFCH3+.
- Forsyth, David A.,Lucas, Peter,Burk, Robert M.
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p. 240 - 245
(2007/10/02)
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