- FARNESOID X RECEPTOR AGONISTS AND USES THEREOF
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Described herein are compounds that are farnesoid X receptor agonists, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity.
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Paragraph 00481; 00483
(2020/04/25)
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- σ-Bond Hydroboration of Cyclopropanes
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Hydroboration of alkenes is a classical reaction in organic synthesis in which alkenes react with boranes to give alkylboranes with subsequent oxidation resulting in alcohols. The double bond (π-bond) of alkenes can be readily reacted with boranes owing to its high reactivity. However, the single bond (σ-bond) of alkanes has never been reacted. To pursue the development of σ-bond cleavage, we selected cyclopropanes as model substrates since they present a relatively weak σ-bond. Herein, we describe an iridium-catalyzed hydroboration of cyclopropanes, resulting in β-methyl alkylboronates. These unusually branched boronates can be derivatized by oxidation or cross-coupling chemistry, accessing "designer"products that are desired by practitioners of natural product synthesis and medicinal chemistry. Furthermore, mechanistic investigations and theoretical studies revealed the enabling role of the catalyst.
- Arifin,Itami, Kenichiro,Kato, Hiroki,Kobayashi, Chisa,Kondo, Hiroki,Matsushita, Kaoru,Miyamura, Shin,Yamaguchi, Junichiro,Yokogawa, Daisuke
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supporting information
p. 11306 - 11313
(2020/07/13)
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- Metal-Free Photoinduced Hydroalkylation Cascade Enabled by an Electron-Donor-Acceptor Complex
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A metal- A nd photocatalyst-free photoinduced radical cascade hydroalkylation of 1,7-enynes has been disclosed. The process is triggered by a single electron transfer (SET) event involving a photoexcited electron-donor-acceptor complex between an NHPI ester and a Hantzsch ester, which decomposes to afford a tertiary radical that is readily trapped by the enyne. The method provides an operationally simple, robust, and step-economical approach toward the construction of diversely functionalized dihydroquinolinones bearing quaternary centers. A sequential one-pot hydroalkylation-isomerization approach is also offered, giving access to a family of quinolinones. A wide substrate scope and high functional group tolerance were observed in both approaches.
- Correia, José Tiago M.,Piva Da Silva, Gustavo,Kisukuri, Camila M.,André, Elias,Pires, Bruno,Carneiro, Pablo S.,Paixa?, Márcio W.
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p. 9820 - 9834
(2020/09/03)
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- Optimization of Acetazolamide-Based Scaffold as Potent Inhibitors of Vancomycin-Resistant Enterococcus
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Vancomycin-resistant enterococci (VRE) are the second leading cause of hospital-acquired infections (HAIs) attributed to a drug-resistant bacterium in the United States, and resistance to the frontline treatments is well documented. To combat VRE, we have repurposed the FDA-approved carbonic anhydrase drug acetazolamide to design potent antienterococcal agents. Through structure-activity relationship optimization we have arrived at two leads possessing improved potency against clinical VRE strains from MIC = 2 μg/mL (acetazolamide) to MIC = 0.007 μg/mL (22) and 1 μg/mL (26). Physicochemical properties were modified to design leads that have either high oral bioavailability to treat systemic infections or low intestinal permeability to treat VRE infections in the gastrointestinal tract. Our data suggest the intracellular targets for the molecules are putative α-carbonic and γ-carbonic anhydrases, and homology modeling and molecular dynamics simulations were performed. Together, this study presents potential anti-VRE therapeutic options to provide alternatives for problematic VRE infections.
- Kaur, Jatinder,Cao, Xufeng,Abutaleb, Nader S.,Elkashif, Ahmed,Graboski, Amanda L.,Krabill, Aaron D.,Abdelkhalek, Ahmed Hassan,An, Weiwei,Bhardwaj, Atul,Seleem, Mohamed N.,Flaherty, Daniel P.
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p. 9540 - 9562
(2020/10/19)
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- 2-Amino-5,6-difluorophenyl-1 H-pyrazole-Directed PdII Catalysis: Arylation of Unactivated β-C(sp3)-H Bonds
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Palladium-catalyzed arylation of unactivated β-C(sp3)-H bonds in carboxylic acid derivatives with aryl iodides is described for the first time using 2-amino-5,6-difluorophenyl-1H-pyrazole as an efficient and readily removable directing group. Two fluoro groups are installed at the 5- and 6-position of the anilino moiety in 2-aminophenyl-1H-pyrazole, clearly enhancing the directing ability of the auxiliary. In addition, the protocol employs Cu(OAc)2/Ag3PO4 (1.2/0.3) as additives, evidently reducing the stoichiometric amount of expensive silver salts. Furthermore, this process exhibits high β-site selectivity, compatibility with diverse substrates containing α-hydrogen atoms, and excellent functional group tolerance.
- Yang, Jinyue,Fu, Xiaopan,Tang, Shibiao,Deng, Kezuan,Zhang, Lili,Yang, Xianjin,Ji, Yafei
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p. 10221 - 10236
(2019/08/20)
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- Fenhexamid and analysis method thereof
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The invention discloses fenhexamid and an analysis method thereof. The fenhexamid is prepared from aniline, hydrochloric acid, sodium nitrite solution, 2,3-dichlorophenol, sodium hydroxide, water, ethyl alcohol, sodium hydrosulfite, 1-methyl cyclohexanoic acid, methylene dichloride, N,N-dimethyl formamide, thionyl chloride, ethyl acetate and triethylamine. The fenhexamid content reaches 98% or above, and yield reaches 86-87%; in a fenhexamid analysis process, sodium hydrosulfite adopted for azo reduction for generating 2,3-dichloro-4-hydroxylaniline is high in reducibility and quick in weak alkaline reduction reaction, and the conversion rate reaches 98% or above by cross input of sodium hydroxide and sodium hydrosulfite; pH is kept in a range of 6-7 by acid reflux after adding of sodium hydrosulfite. Fenhexamid production conditions are mild, and easiness in operation, high safety, high total yield, low cost and suitableness for large-scale production and application to enterprises are realized.
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Paragraph 0053; 0061-0062; 0070; 0077
(2018/11/03)
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- Palladium-catalyzed C(carbonyl)-C bond cleavage of amides: a facile access to phenylcarbamate derivatives with alcohols
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A sulfur-containing auxiliary enabled palladium-catalyzed C(carbonyl)-C bond activation of amides was reported to form phenylcarbamate derivatives with alcohols. Both alkyl and benzyl alcohols could be employed well with yields up to 85%. Derivations from phenylcarbamates to ureas and thiocarbamates illustrated the potential applications of this sequential C-C cleavage/C-O coupling reaction.
- Yan, Xufei,Sun, Huihui,Xiang, Haifeng,Yu, Da-Gang,Luo, Daibing,Zhou, Xiangge
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supporting information
p. 8606 - 8609
(2018/08/06)
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- Domino Pd0-Catalyzed C(sp3)–H Arylation/Electrocyclic Reactions via Benzazetidine Intermediates
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The Pd0-catalyzed C(sp3)-H arylation of 2-bromo-N-methylanilides leads to unstable benzazetidine intermediates that rearrange to benzoxazines through 4π electrocyclic ring-opening and 6π electrocyclization. The introduction of a bulky, non-activatable amide group on the nitrogen atom was key to favor the challenging reductive elimination step and disfavor undesired reaction pathways.
- Rocaboy, Ronan,Dailler, David,Zellweger, Florian,Neuburger, Markus,Salomé, Christophe,Clot, Eric,Baudoin, Olivier
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supporting information
p. 12131 - 12135
(2018/09/11)
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- Nickel-Catalyzed oxidative coupling of unactivated C(sp3)-H bonds in aliphatic amides with terminal alkynes
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In this work, we demonstrated Ni-catalyzed oxidative coupling of unactivated C(sp3)-H bonds with terminal alkynes for construction of C(sp3)-C(sp) bonds to synthesize alkyl-substituted internal alkynes. Different amides exhibited good compatibility. Preliminary mechanistic studies were conducted to account for this alkynylation.
- Luo, Fei-Xian,Cao, Zhi-Chao,Zhao, Hong-Wei,Wang, Ding,Zhang, Yun-Fei,Xu, Xing,Shi, Zhang-Jie
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supporting information
p. 18 - 21
(2017/04/04)
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- A General Approach to Quaternary Center Construction from Couplings of Unactivated Alkenes and Acyl Xanthates
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A general, radical-mediated approach to quaternary center construction using unactivated alkenes as coupling partners is reported. In this strategy, acyl xanthates, readily accessed from carboxylic acids, serve as precursors to tertiary radicals. This strategy leverages the unique reactivity of xanthates to participate in efficient radical-mediated additions to unactivated alkenes, expanding the scope of quaternary center construction.
- Jenkins, Ernest N.,Czaplyski, William L.,Alexanian, Erik J.
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supporting information
p. 2350 - 2353
(2017/05/12)
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- Nickel-catalysed direct alkylation of thiophenes via double C(sp3)-H/C(sp2)-H bond cleavage: The importance of KH2PO4
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A Ni-catalyzed oxidative C-H/C-H cross-dehydrogenative coupling (CDC) reaction was developed for constructing various highly functionalized alkyl (aryl)-substituted thiophenes. This method employs thiophenes and aliphatic (aromatic) amides that contain an 8-aminoquinoline as a removable directing group in the presence of a silver oxidant. The approach enables the facile one-step synthesis of substituted thiophenes with high functional group compatibility via double C-H bond cleavage without affecting C-Br and C-I bonds. DFT calculations verify the importance of KH2PO4 as an additive for promoting C-H bond cleavage and support the involvement of a Ni(iii) species in the reaction.
- Wang, Xie,Xie, Peipei,Qiu, Renhua,Zhu, Longzhi,Liu, Ting,Li, You,Iwasaki, Takanori,Au, Chak-Tong,Xu, Xinhua,Xia, Yuanzhi,Yin, Shuang-Feng,Kambe, Nobuaki
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supporting information
p. 8316 - 8319
(2017/07/26)
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- Thioamide-Directed Cobalt(III)-Catalyzed Selective Amidation of C(sp3)?H Bonds
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A mild, oxidant-free, and selective Cp*CoIII-catalyzed amidation of thioamides with robust dioxazolone amidating agents via C(sp3)?H bond activation to generate the desired amidated products is reported. The method is efficient and allows for the C?H amidation of a wide range of functionalized thioamides with aryl-, heteroaryl-, and alkyl-substituted dioxazolones under the Cp*CoIII-catalyzed conditions. The observed regioselectivity towards primary C(sp3)?H activation is supported by computational studies and the cyclometalation is proposed to proceed by means of an external carboxylate-assisted concerted metalation/deprotonation mechanism. The reported method is a rare example of the use of a directing group other than the commonly used pyridine and quinolone classes for Cp*CoIII-catalyzed C(sp3)?H functionalization and the first to exploit thioamides.
- Tan, Peng Wen,Mak, Adrian M.,Sullivan, Michael B.,Dixon, Darren J.,Seayad, Jayasree
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supporting information
p. 16550 - 16554
(2017/12/07)
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- Copper(II)/Silver(I)-Catalyzed Sequential Alkynylation and Annulation of Aliphatic Amides with Alkynyl Carboxylic Acids: Efficient Synthesis of Pyrrolidones
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A highly efficient protocol for the synthesis of pyrrolidones by the copper-catalyzed alkynylation/annulation of aliphatic amides with alkynyl carboxylic acids is discussed in this paper. A broad range of easily accessible alkynyl carboxylic acids were introduced at the β-methyl group of aliphatic amides with the assistance of an 8-aminoquinolyl auxiliary group via decarboxylation to achieve the subsequent cyclic C-N bond formation within one hour. High selectivity of β-methyl groups over methylene groups was observed, and the extension of this catalytic system to the activation of methylene C-H bonds failed. The substrates with two different groups at the α-position of the aliphatic amides lead to the formation of diastereoisomers which is determined by 1H NMR spectroscopy. The initially produced products with Z-configurations can be easily transformed to the corresponding products with E-configurations by the treatment with dilute p-toluenesulfonic acid after the reaction. This catalytic tandem decarboxylative cyclization provides a new opportunity for the direct functionalization of sp3 C-H bonds.
- Zhang, Jitan,Li, Danyang,Chen, Hui,Wang, Binjie,Liu, Zhanxiang,Zhang, Yuhong
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supporting information
p. 792 - 807
(2016/03/09)
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- A C-H Insertion Approach to Functionalized Cyclopentenones
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Cyclopentenones are synthetically versatile structures, and their straightforward construction from alkynone substrates by employing synthetically streamlining C-H insertion is conceptually appealing and of high synthetic potential. But, its implementation is very limited. Herein we report a Au-catalyzed version, which affords 2-bromocyclopent-2-en-1-ones with a broad scope and synthetically desirable diastereoselectivities. The proposed key intermediate capable of the observed insertion into unactivated C-H bonds is a fully functionalized gold vinylidene, which is generated via a novel intermolecular strategy. This flexible access of likely gold vinylidenes opens various opportunities to explore their versatile reactivities.
- Wang, Youliang,Zarca, Maxence,Gong, Liu-Zhu,Zhang, Liming
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supporting information
p. 7516 - 7519
(2016/07/06)
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- Nickel-catalyzed direct thioetherification of β-C(sp3)-H bonds of aliphatic amides
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The nickel-catalyzed β-thioetherification of unactivated C(sp3)-H bond of propionamides is established with the assistance of 8-aminoquinoline auxiliary, leading to the β-thio carboxylic acid derivatives. A broad range of functional groups is compatible with this thioetherfication reaction. The process represents the first successful example of metal-catalyzed C-S bond formation from unactivated C(sp3)-H bonds.
- Lin, Cong,Yu, Wenlong,Yao, Jinzhong,Wang, Bingjie,Liu, Zhanxiang,Zhang, Yuhong
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supporting information
p. 1340 - 1343
(2015/03/14)
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- Nickel-Catalyzed Addition-Type Alkenylation of Unactivated, Aliphatic C-H Bonds with Alkynes: A Concise Route to Polysubstituted γ-Butyrolactones
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(Chemical Equation Presented). Through the nickel-catalyzed chelation-assisted C-H bond activation strategy, the addition-type alkenylation of unreactive β-C(sp3)-H bonds of aliphatic amides with internal alkynes is developed for the first time to produce γ,δ-unsaturated carboxylic amide derivatives. The resulting alkenylated products can further be transformed into polysubstituted γ-butyrolactones with pyridinium chlorochromate (PCC).
- Li, Mingliang,Yang, Yudong,Zhou, Danni,Wan, Danyang,You, Jingsong
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supporting information
p. 2546 - 2549
(2015/05/27)
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- Synthesis of oxazolines from amides via palladium-catalyzed functionalization of unactivated C(sp3)-H bond
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A complementary method that enables the expeditious synthesis of oxazolines from amides via Pd-catalyzed C(sp3)-H functionalization has been described. Preliminary studies indicate that the reaction might go through a chlorination/nucleophilic cyclization sequence, and the high efficiency of this sequence is enhanced by the in situ cyclative capture of the chlorinated intermediate. The resulting oxazolines can be further converted into the corresponding β-amino alcohols without chromatography.
- Li, Bo,Wang, Si-Qing,Liu, Bin,Shi, Bing-Feng
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supporting information
p. 1200 - 1203
(2015/03/14)
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- Nickel-catalyzed direct thiolation of C(sp3)-H bonds in aliphatic amides
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Nickel-catalyzed thiolation of the inactivated methyl C(sp3)-H bonds of aliphatic amides with disulfide is described. It is a novel strategy for the synthesis of thioethers with the ultimate goal of generating thioether carboxylic acids with various functional groups.
- Wang, Xie,Qiu, Renhua,Yan, Chunyang,Reddy, Vutukuri Prakash,Zhu, Longzhi,Xu, Xinhua,Yin, Shuang-Feng
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supporting information
p. 1970 - 1973
(2015/04/27)
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- Nickel-catalyzed direct thiolation of unactivated C(sp3)-H bonds with disulfides
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The first nickel-catalyzed thiolation of unactivated C(sp3)-H bonds with disulfides was described. This transformation uses (dppp)NiCl2 as a catalyst and BINOL as a ligand, which are efficient for the thiolation of β-methyl C(sp
- Yan, Sheng-Yi,Liu, Yue-Jin,Liu, Bin,Liu, Yan-Hua,Zhang, Zhuo-Zhuo,Shi, Bing-Feng
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supporting information
p. 7341 - 7344
(2015/04/27)
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- Nickel-catalyzed directed sulfenylation of sp2 and sp3 C-H bonds
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Directed sulfenylation of both sp2 and sp3 C-H bonds was achieved through nickel catalyzed directed C-S bond formation, giving the desired product in good to excellent yield (up to 90%). Other metal cations, including Cu, Fe, Pd, Rh, Ru and Co, gave almost no reaction under identical conditions, which highlighted the unique reactivity of this Ni system.
- Ye, Xiaohan,Petersen, Jeffrey L.,Shi, Xiaodong
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supporting information
p. 7863 - 7866
(2015/05/13)
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- Palladium(0)/PAr3-catalyzed intermolecular amination of C(sp3)-H bonds: Synthesis of β-amino acids
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An intermolecular C(sp3)-H amination using a Pd0/PAr3 catalyst was developed. The reaction begins with oxidative addition of R2N-OBz to a Pd0/PAr3 catalyst and subsequent cleavage of a C(sp3)-H bond by the generated Pd-NR2 intermediate. The catalytic cycle proceeds without the need for external oxidants in a similar manner to the extensively studied palladium(0)-catalyzed C-H arylation reactions. The electron-deficient triarylphosphine ligand is crucial for this C(sp3)-H amination reaction to occur.
- He, Jian,Shigenari, Toshihiko,Yu, Jin-Quan
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supporting information
p. 6545 - 6549
(2015/06/08)
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- Copper-mediated aryloxylation and vinyloxylation of β-C(sp3)-H bond of propionamides with organosilanes
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A novel copper-mediated method for the aryloxylation and vinyloxylation of β-C(sp3)-H bonds of propioamides with organosilanes is described. The reaction proceeds with the assistance of an 8-aminoquinolyl auxiliary in a tandem way by the first oxidation of β-C(sp3)-H bonds and subsequent arylation/vinylation to give the aryloxylation/vinyloxylation products. This unusual aryloxy/vinyloxy forming reaction offers a new avenue for the functionalization of unactivated sp3 C-H bonds in organic synthesis.
- Zhang, Jitan,Chen, Hui,Wang, Binjie,Liu, Zhanxiang,Zhang, Yuhong
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supporting information
p. 2768 - 2771
(2015/06/16)
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- Cobalt-Catalyzed Cyclization of Aliphatic Amides and Terminal Alkynes with Silver-Cocatalyst
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A new method of cobalt-catalyzed synthesis of pyrrolidinones from aliphatic amides and terminal alkynes was discovered through a C-H bond functionalization process on unactivated sp3 carbons with the silver cocatalyst using a bidentate auxiliary. For the first time, a broad range of easily accessible alkynes are exploited as the reaction partner in C(sp3)-H bond activation to give the important 5-ethylidene-pyrrolidin-2-ones in a site-selective fashion. The reaction tolerates a wide variety of functional groups including -F, -Cl, -Br, -CF3, ether, cyclopropane, and thiophene. Both pyridine ligand and aromatic solvent play the important role for the promotion of reactivity. This cobalt-catalyzed cyclization reaction can be successfully extended to a variety of aromatic amides to afford a variety of isoindolinones. Attractive features of this catalytic system include its low cost, easy operation, and convenient access to a wide range of pyrrolidinones and isoindolinones.
- Zhang, Jitan,Chen, Hui,Lin, Cong,Liu, Zhanxiang,Wang, Chen,Zhang, Yuhong
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supporting information
p. 12990 - 12996
(2015/10/28)
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- Readily Removable Directing Group Assisted Chemo- and Regioselective C(sp3)-H Activation by Palladium Catalysis
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Currently used directing groups for selective aliphatic β-functionalization of carbonyl compounds show excellent reactivity and selectivity with an amide as a linker. Described herein is 2-piconimide, used for the first time with commercially available 2-picolinamide/2-picolic acid as precursors, to direct C-H arylation/alkenylation by palladium catalysis. The directing group is essential for promoting the sequnetial primary and secondary C(sp3)-H arylation with different aryl iodides in one substrate. The directing group was easily removed under simple reaction conditions at room temperature.
- Zhang, Yun-Fei,Zhao, Hong-Wei,Wang, Hui,Wei, Jiang-Bo,Shi, Zhang-Jie
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supporting information
p. 13686 - 13690
(2015/11/16)
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- Nickel-Catalyzed Direct C (sp3)-H Arylation of Aliphatic Amides with Thiophenes
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Nickel-catalyzed heteroarylation of the inactive methyl C(sp3)-H bond of aliphatic amide with heteroarenes is described. The method takes advantage of chelation assistance by an 8-aminoquinolinyl moiety. The synthetic reaction has good tolerance toward functional groups, and it can be used in the construction of various kinds of alkyl-substituted heteroarenes.
- Wang, Xie,Zhu, Longzhi,Chen, Sihai,Xu, Xinhua,Au, Chak-Tong,Qiu, Renhua
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supporting information
p. 5228 - 5231
(2015/11/18)
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- Nickel-catalyzed direct arylation of C(sp3)-H bonds in aliphatic amides via bidentate-chelation assistance
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The Ni-catalyzed, direct arylation of C(sp3)-H (methyl and methylene) bonds in aliphatic amides containing an 8-aminoquinoline moiety as a bidentate directing group with aryl halides is described. Deuterium-labeling experiments indicate that the C-H bond cleavage step is fast and reversible. Various nickel complexes including both Ni(II) and Ni(0) show a high catalytic activity. The results of a series of mechanistic experiments indicate that the catalytic reaction does not proceed through a Ni(0)/Ni(II) catalytic cycle, but probably through a Ni(II)/Ni(IV) catalytic cycle.
- Aihara, Yoshinori,Chatani, Naoto
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supporting information
p. 898 - 901
(2014/02/14)
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- Copper-catalyzed intramolecular C(sp3)-H and C(sp2)-H amidation by oxidative cyclization
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The first copper-catalyzed intramolecular C(sp3)-H and C(sp 2)-H oxidative amidation has been developed. Using a Cu(OAc) 2 catalyst and an Ag2CO3 oxidant in dichloroethane solvent, C(sp3)-H
- Wang, Zhen,Ni, Jizhi,Kuninobu, Yoichiro,Kanai, Motomu
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supporting information
p. 3496 - 3499
(2014/04/03)
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- Palladium-catalyzed C(sp3)-H activation: A facile method for the synthesis of 3,4-dihydroquinolinone derivatives
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3,4-Dihydroquinolinones were synthesized by the palladium-catalyzed, oxidative-addition-initiated activation and arylation of inert C(sp 3)-H bonds. Pd(OAc)2 and P(o-tol)3 were used as the catalyst and ligand, respectively, to improve the efficiency of the reaction. A further advantage of this reaction is that it could be performed in air. A relatively rare seven-membered palladacycle was proposed as a key intermediate of the catalytic cycle.
- Yan, Jia-Xuan,Li, Hu,Liu, Xiang-Wei,Shi, Jiang-Ling,Wang, Xin,Shi, Zhang-Jie
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supporting information
p. 4945 - 4949
(2014/05/20)
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- Iron-catalyzed C(sp2)-H and C(sp3)-H arylation by triazole assistance
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Modular 1,2,3-triazoles enabled iron-catalyzed C-H arylations with broad scope. The novel triazole-based bidentate auxiliary is easily accessible in a highly modular fashion and allowed for user-friendly iron-catalyzed C(sp 2)-H functionalizations of arenes and alkenes with excellent chemo- and diastereoselectivities. The versatile iron catalyst also proved applicable for challenging C(sp3)-H functionalizations, and proceeds by an organometallic mode of action. The triazole-assisted C-H activation strategy occurred under remarkably mild reaction conditions, and the auxiliary was easily removed in a traceless fashion. Intriguingly, the triazole group proved superior to previously used auxiliaries. With a little help: A versatile iron catalyst allows the arylation of C(sp2)-H and C(sp3)-H bonds in the presence of a modular and removable triazolyldimethylmethyl (TAM) auxiliary, whose structure can be varied through 1,3-dipolar azide-alkyne cycloadditions.
- Gu, Qing,Al Mamari, Hamad H.,Graczyk, Karolina,Diers, Emelyne,Ackermann, Lutz
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supporting information
p. 3868 - 3871
(2014/05/06)
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- β-Arylation of carboxamides via iron-catalyzed C(sp3)-H bond activation
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A 2,2-disubstituted propionamide bearing an 8-aminoquinolinyl group as the amide moiety can be arylated at the β-methyl position with an organozinc reagent in the presence of an organic oxidant, a catalytic amount of an iron salt, and a biphosphine ligand at 50 C. Various features of selectivity and reactivity suggest the formation of an organometallic intermediate via rate-determining C-H bond cleavage rather than a free-radical-type reaction pathway.
- Shang, Rui,Ilies, Laurean,Matsumoto, Arimasa,Nakamura, Eiichi
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supporting information
p. 6030 - 6032,3
(2013/05/22)
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- Highly regioselective carbonylation of unactivated C(sp3)-H bonds by ruthenium carbonyl
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The regioselective carbonylation of unactivated C(sp3)-H bonds of aliphatic amides was achieved using Ru3(CO)12 as a catalyst. The presence of a 2-pyridinylmethylamine moiety in the amide is crucial for a successful reaction. The reaction shows a preference for C-H bonds of methyl groups as opposed to methylene C-H bonds and tolerates a variety of functional groups. The stoichiometric reaction of an amide with Ru 3(CO)12 gave a dinuclear ruthenium complex in which the 2-pyridinylmethylamino moiety was coordinated to the ruthenium center in an N,N manner.
- Hasegawa, Nao,Charra, Valentine,Inoue, Satoshi,Fukumoto, Yoshiya,Chatani, Naoto
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supporting information; experimental part
p. 8070 - 8073
(2011/07/08)
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- N-directed aliphatic C-H borylation using borenium cation equivalents
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Highly electrophilic boron cations derived from hindered amine borane complexes have been shown to undergo intramolecular aliphatic C-H borylation.
- Prokofjevs, Aleksandrs,Vedejs, Edwin
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supporting information; experimental part
p. 20056 - 20059
(2012/02/05)
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- Phenyl-1,2,4-Oxadiazolone Derivatives, Processes For Their Preparation and Methods For Their Use as Pharmaceuticals
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The inventive compounds of the present invention are comprised of phenyl and pyridinyl-1,2,4-oxadiazolone derivatives and their physiologically acceptable salts and functional derivatives that are shown to provide peroxisome proliferator activator recepto
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Page/Page column 51
(2008/12/04)
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- Synthesis of β-, γ-, and δ-lactams via Pd(II)-catalyzed C-H activation reactions
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Pd(II)-catalyzed intramolecular amination of sp2 and sp3 C-H bonds are developed using a combination of CuCl2 and AgOAc as the oxidant. The reaction protocol tolerates the presence of a double bond in the substrates. This catalytic reaction provides practical access to a wide range of β-, γ-, and δ-lactams. Copyright
- Wasa, Masayuki,Yu, Jin-Quan
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supporting information; experimental part
p. 14058 - 14059
(2009/03/11)
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- INHIBITORS OF SERINE PALMITOYLTRANSFERASE
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This invention provides compounds of the formula (I) useful in the inhibition or modulation of serine palmitoyl transferase and their use in methods of treatment or amelioration of type 2 diabetes, type 1 diabetes, insulin resistance, the effects of obesity, metabolic syndrome (sometimes referred to as Syndrome X), impaired glucose tolerance, Cushing's disease, cardiovascular disease, prothrombotic conditions, myocardial infarction, hypertension, congestive heart failure, cardiomyopathy, atherosclerosis, dyslipidemia, sepsis, liver damage, retinal degenerative disorders, cachexia, emphysema, hepatitis C infections, HIV infections and inflammatory disorders and useful in methods for raising HDL plasma levels in a mammal. The compounds of this invention can also be used to prevent damage or loss of pancreatic islet beta cells (such as in the case of pancreatic beta cell apoptosis, including those related to insulin-dependent diabetes mellitus).
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Page/Page column 50
(2008/12/07)
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- Design and synthesis of novel imidazoline derivatives with potent antihyperglycemic activity in a rat model of type 2 diabetes
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Imidazoline derivatives have been reported to show antihyperglycemic activity in vivo. In the present study, we first showed that there was no correlation between the in vivo antidiabetic activity and the in vitro affinities for the I1/I2
- Crane, Louis,Anastassiadou, Maria,Hage, Salome El,Stigliani, Jean Luc,Baziard-Mouysset, Genevieve,Payard, Marc,Leger, Jean Michel,Bizot-Espiard, Jean-Guy,Ktorza, Alain,Caignard, Daniel-Henri,Renard, Pierre
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p. 7419 - 7433
(2007/10/03)
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- CATALYTICS ASYMMETRIC ACTIVATION OF UNACTIVATED C-H BONDS, AND COMPOUNDS RELATED THERETO
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One aspect of the present invention is directed in part to catalytic and stereoselective functionalization of unactivated C-H bonds of simple organic substrates. The compounds and methods provided herein allow one to control the stereochemistry in a C-H activation step, activate substrates containing α-hydrogens next to the directing group, and remove a directing group under mild conditions. One aspect of the present invention relates to a transition-metal-catalyzed method for selective and asymmetric oxidation of carbons located in a β- or γ-position relative to an auxiliary. Another aspect of the invention relates to the enantiomerically-enriched substrates and the enantiomerically-enriched products formed via said method. In certain embodiments, oxazoline and oxazinone directing groups are used. In addition, the Boc protecting group has been identified as a directing group which does not necessitate removal.
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Page/Page column 76-77
(2010/10/20)
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- Palladium-catalyzed asymmetric iodination of unactivated C-H bonds under mild conditions
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(Chemical Equation Presented) Specific, asymmetric, and mild: Oxazoline (Oxa), a removable chelating chiral auxiliary, assists in the asymmetric activation of C(sp3)-H bonds at the β position and C(sp 2)-H bonds at the γ position. Pd-(OAc)2 is an effective catalyst for the selective and asymmetric iodination of methyl, cyclopropyl, and aryl groups at room temperature (see formulae).
- Giri, Ramesh,Chen, Xiao,Yu, Jin-Quan
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p. 2112 - 2115
(2007/10/03)
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- Pyrazole urea-based inhibitors of p38 MAP kinase: From lead compound to clinical candidate
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We report on a series of N-pyrazole, N′-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5′-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.
- Regan, John,Moss, Neil,Pargellis, Chris,Pav, Sue,Proto, Alfred,Swinamer, Alan,Tong, Liang,Torcellini, Carol,Breitfelder, Steffen,Cirillo, Pier,Gilmore, Thomas,Graham, Anne G.,Hickey, Eugene,Klaus, Bernhard,Madwed, Jeffrey,Moriak, Monica
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p. 2994 - 3008
(2007/10/03)
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- Bis(2-(acylamino)phenyl) disulfides, 2-(acylamino)benzenethiols, and S-(2-(acylamino)phenyl) alkanethioates as novel inhibitors of cholesteryl ester transfer protein
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A series of bis(2-(acylamino)phenyl) disulfides, 2-(acylamino)benzenethiols, S-(2-(acylamino)-phenyl) alkanethioates, and related compounds were synthesized, and their inhibitory effect on cholesteryl ester transfer protein activity in human plasma was evaluated. This study elucidated the structural requirements for inhibitory activity and determined that the optimum compound was S-(2-((1-(2-ethylbutyl)cyclohexane)carbonylamino)phenyl) 2-methylpropanethioate (27) (JTT-705). This compound achieved 50% inhibition of CETP activity in human plasma at a concentration of 9 μM and 95% inhibition of CETP activity in male Japanese white rabbits at an oral dose of 30 mg/kg. It increased the plasma HDL cholesterol level by 27% and 54%, respectively, when given at oral doses of 30 or 100 mg/kg once a day for 3 days to male Japanese white rabbits.
- Shinkai,Maeda,Yamasaki,Okamoto,Uchida
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p. 3566 - 3572
(2007/10/03)
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- 4-INDOLYLPIPERAZINYL DERIVATIVES
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This invention provides anxiolytic/antidepressant agents of the formula: STR1 in which R 1 is alkyl;R 2 and R 3 are alkyl or taken together they are polymethylene; R 4 is hydrogen or alkyl;R 5 is phenyl, benzyl, substituted phenyl, or s
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- Decarboxylative radical addition to vinylsulphones and vinylphosphonium bromide: Some further novel transformations of geminal (pyridine-2-thiyl) phenylsulphones
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Irradiation of O-acyl derivatives 1 of N-hydroxy-2-thiopyridone with visible light in the presence of phenyl vinyl sulphone or vinyl triphenylphosphonium bromide leads to the corresponding adducts 8 and 9 which can undergo a wide variety of further transformations.
- Barton,Boivin,Crepon nee da Silva,Sarma,Togo,Zard
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p. 7091 - 7108
(2007/10/02)
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- THE INVENTION OF NEW RADICAL CHAIN REACTIONS. PART XIII. HIGH YIELDING DECARBOXYLATIVE CHALCOGENATION OF ALIPHATIC AND ALICYCLIC ACIDS
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Irradiation with a tungsten lamp of mixed anhydrides (e.g. 8) derived from aliphatic or alicyclic carboxylic acids and N-hydroxy-2-pyridine thione 3 in the presence of a disulphide, diselenide or ditelluride gives the corresponding chalcogenide (e.g. 9, 10, or 11) in high yield.The process involves a radical decarboxylation followed by SH2 reaction of the intermediate carbon radical on the dichalcogenide.
- Barton, Derek H.R.,Bridon, Dominique,Zard, Samir Z.
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p. 449 - 462
(2007/10/02)
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- Cyclopentanone Synthesis by Intramolecular Carbon-Hydrogen Insertion of Diazo Ketones. A Diterpene-to-Steroid Skeleton Conversion
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Intramolecular carbon-hydrogen insertion on cupric sulfate assisted decomposition of diazomethyl ketones derived from four 1-methylcycloalkanecarboxylic acids and (hexahydrophenyl)acetic, homopivalic, and enanthic acids is shown to yield mostly cyclopentanones.The yields are appreciable in the conformationally favorable cases, and insertion in the solvent cyclohexane can be avoided by the use of Freon TF as the solvent.The conversion of a primaradienic diterpene into a 14-iso-16-androstanone derivative shows the power of the new method of cyclopentanone synthesis.
- Wenkert, Ernest,Davis, Linda L.,Mylari, Banavara L.,Solomon, Mary F.,Silva, Roberto R. da,et al.
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p. 3242 - 3247
(2007/10/02)
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