- Rhodium(III)-Catalyzed Aerobic Oxidative C-H Olefination of Unsaturated Acrylamides with Unactivated Olefins
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A rhodium(III)-catalyzed aerobic oxidative cross-coupling of acrylamides with unactivated alkenes via vinylic C-H activation has been developed. The present cross-coupling reaction was examined with a variety of differently functionalized acrylamides and unactivated olefins. In these reactions, highly valuable amide-functionalized butadienes were prepared in good to excellent yields. This protocol was also compatible with Weinreb amides. A possible reaction mechanism involving the chelation-assisted vinylic C-H activation via a carboxylate-assisted deprotonation pathway is proposed.
- Logeswaran, Ravichandran,Jeganmohan, Masilamani
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supporting information
p. 767 - 771
(2021/02/06)
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- Effect of Transition Metals on Chemodivergent Cross-Coupling of Acrylamides with Vinyl Acetate via C-H Activation
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A novel chemodivergent cross-coupling of acrylamides and vinyl acetates has been realized via metal-catalyzed vinylic C-H activation. The selective olefinic C-H vinylation and alkenylation reaction was examined with a variety of differently functionalized acrylamides. The reaction efficiently generates a range of highly synthetically valuable butadienes with good functional group tolerance in good to moderate yields. A possible catalytic reaction mechanism involving the chelation-assisted olefinic C-H activation via an acetate-assisted deprotonation pathway is proposed.
- Logeswaran, Ravichandran,Jeganmohan, Masilamani
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supporting information
p. 5679 - 5683
(2021/08/03)
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- Rhodium(III)-catalyzed chemodivergent annulations between phenyloxazoles and diazos via C–H activation
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Acid-controlled, chemodivergent and redox-neutral annulations for the synthesis of isocoumarins and isoquinolinones have been realized via Rh(III)-catalyzed C[sbnd]H activation. Diazo compounds act as a carbene precursor, and coupling occurs in one-pot process, where adipic acid and trimethylacetic acid promote chemodivergent cyclizations.
- Zhang, Xueguo,Wang, Peigen,Zhu, Liangwei,Chen, Baohua
-
supporting information
p. 695 - 699
(2020/06/28)
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- RhIII-Catalyzed C-H (Het)arylation/Vinylation of N-2,6-Difluoroaryl Acrylamides
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RhIII-catalyzed sp2 C-H cross-coupling of acrylamides with organoboron reactants has been accomplished using a commercially available N-2,6-difluoroaryl acrylamide auxiliary. A broad range of aryl and vinyl boronates as well as a variety of heterocyclic boronates with strong coordinating ability can serve as the coupling partners. This transformation proceeds under moderate reaction conditions with excellent functional group tolerance and high regioselectivity.
- Wang, Huai-Wei,Qiao, Yu-Han,Wu, Jia-Xue,Wang, Qiu-Ping,Tian, Meng-Xin,Li, Yong-Fei,Yao, Qing-Xia,Li, Da-Cheng,Dou, Jian-Min,Lu, Yi
-
supporting information
p. 656 - 662
(2021/02/01)
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- Unified total syntheses of (±)-sessilifoliamides B, C, and D
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The first total syntheses of the Stemona alkaloids sessilifoliamides B and D and the second synthesis of sessilifoliamide C have been completed from a simple pyrrole substrate. The bicyclic lactam core was prepared on a gram scale via a Br?nsted acid mediated cyclization and controlled oxidation with Dess-Martin periodinane. This delivered sessilifoliamide C (and its C-11 epimer) in 24% yield over 11 steps, and sessilifoliamides B and D in 13 and 17 steps, respectively.
- Olivier, Wesley J.,Bissember, Alex C.,Smith, Jason A.
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supporting information
p. 3437 - 3441
(2021/05/10)
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- Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities
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Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC50= 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC50= 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.
- Feng, Jia-Hao,He, Qi-Wei,Hou, Ji-Qin,Hu, Xiao-Long,Long, Huan,Wang, Bao-Lin,Wang, Hao,Wang, Quan,Wang, Rong,Ye, Wen-Cai,Zhang, Li-Xin,Zhang, Xiao-Qi
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p. 1954 - 1966
(2021/07/20)
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- Preparation method of 2,4,6-trimethylbenzoyl chloride and acyl chloride co-production technology
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The invention relates to the field of new materials of fine chemicals, in particular to 2,4,6-trimethylbenzoyl chloride (also known as trimesoyl chloride) and an environment-friendly and economical novel preparation process technology for co-producing series acyl chloride products.
- -
-
Paragraph 0042-0044
(2020/11/25)
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- Synthesis of Forms of a Chiral Ruthenium Complex Containing a Ru-Colefin(sp2) Bond and Their Application to Catalytic Asymmetric Cyclopropanation Reactions
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Organometallic complexes [Ru-Colefin(sp2)-Ru(II)-Pheox 2a-2d] containing a Ru-Colefin(sp2) bond have been prepared from unsaturated chiral oxazoline derivatives and evaluated for asymmetric cyclopropanation reactions. The corresponding optically active cyclopropanes were obtained with high yields and high stereoselectivities (≥99/2) bond. In particular, Ru(II)-Prox catalyst 2c, in which there was no geminal substituent on the metal, was shown to have the highest enantioselectivities.
- Fujisawa, Ikuhide,Inoue, Hayato,Iwasa, Seiji,Phan Thi Thanh, Nga
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supporting information
(2020/02/15)
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- Direct Regio- and Diastereoselective Synthesis of δ-Lactams from Acrylamides and Unactivated Alkenes Initiated by RhIII-Catalyzed C?H Activation
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We report a RhIII-catalyzed regio- and diastereoselective synthesis of δ-lactams from readily available acrylamide derivatives and unactivated alkenes. The reaction provides a rapid route to a diverse set of δ-lactams in good yield and stereoselectivity, which serve as useful building blocks for substituted piperidines. The regioselectivity of the reaction with unactivated terminal alkene is significantly improved by using Cpt ligand on the RhIII catalyst. The synthetic utility of the reaction is demonstrated by the preparation of a potential drug candidate containing a trisubstituted piperidine moiety. Mechanistic studies show that the reversibility of the C?H activation depends on the choice of Cp ligand on the RhIII catalyst. The irreversible C?H activation is observed and becomes turnover-limiting with [CptRhCl2]2 as catalyst.
- Lee, Sumin,Rovis, Tomislav,Semakul, Natthawat
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supporting information
p. 4965 - 4969
(2020/02/20)
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- Stereospecific Electrophilic Fluorocyclization of α,β-Unsaturated Amides with Selectfluor
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An efficient fluorocyclization of α,β-unsaturated amides through a formal halocyclization process is developed. The reaction proceeds under transition-metal-free conditions and leads to the formation of fluorinated oxazolidine-2,4-diones with excellent regio- and diastereoselectivity. The evaluation of the reaction mechanism based on preliminary experiments and density functional theory calculations suggests that a synergetic syn-oxo-fluorination occurs and is followed by an anti-oxo substitution reaction. The reaction opens a new window in the field of stereospecific fluorofunctionalization.
- Fei, Haiyang,Fu, Yao,Jalani, Hitesh B.,Li, Guigen,Lu, Hongjian,Wu, Hongmiao,Xu, Zheyuan,Zhu, Lin
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supporting information
(2020/03/30)
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- Base-promoted Lewis acid catalyzed synthesis of quinazoline derivatives
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A one-pot protocol has been developed for the synthesis of quinazolinones from amide-oxazolines with TsCl via a cyclic 1,3-azaoxonium intermediate and 6π electron cyclization in the presence of a Lewis acid and base. The process is operationally simple and has a broad substrate scope. This method provides a unique strategy for the construction of quinazolinones.
- Cui, Xin-Feng,Hu, Fang-Peng,Huang, Guo-Sheng,Lu, Guo-Qiang
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supporting information
p. 4376 - 4380
(2020/10/20)
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- Rhodium-Catalyzed Electrooxidative C?H Olefination of Benzamides
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Metal-catalyzed chelation-assisted C?H olefinations have emerged as powerful tools for the construction of functionalized alkenes. Herein, we describe the rhoda-electrocatalyzed C?H activation/alkenylation of arenes. The olefinations of challenging electron-poor benzamides were thus accomplished in a fully dehydrogenative fashion under electrochemical conditions, avoiding stoichiometric chemical oxidants, and with H2 as the only byproduct. This versatile alkenylation reaction also features broad substrate scope and used electricity as a green oxidant.
- Ackermann, Lutz,Struwe, Julia,Zhang, Yan
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supporting information
p. 15076 - 15080
(2020/06/20)
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- Macrolactam Synthesis via Ring-Closing Alkene-Alkene Cross-Coupling Reactions
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Reported herein is a practical method for macrolactam synthesis via a Rh(III)-catalyzed ring closing alkene-alkene cross-coupling reaction. The reaction proceeded via a Rh-catalyzed alkenyl sp2 C-H activation process, which allows access to macrocyclic molecules of different ring sizes. Macrolactams containing a conjugated diene framework could be easily prepared in high chemoselectivities and Z,E stereoselectivities.
- Goh, Jeffrey,Loh, Teck-Peng,Maraswami, Manikantha
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supporting information
p. 9724 - 9728
(2020/12/21)
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- Rh-Catalyzed asymmetric hydroaminomethylation of α-Substituted acrylamides: Application in the synthesis of RWAY
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The successful rhodium-catalyzed asymmetric hydroformylation and hydroaminomethylation of α-substituted acrylamides is described using 1,3-phosphite-phosphoramidite ligands based on a sugar backbone. A broad scope of chiral aldehydes and amines were afforded in high yields and excellent enantioselectivities (up to 99%). Furthermore, the synthetic potential of this method is demonstrated by the single-step synthesis of the brain imaging molecule RWAY.
- B?rner, Armin,Cunillera, Anton,Diéguez, Montserrat,Godard, Cyril,Lutz, Domke,Margalef, Jessica,Miró, Roger,Pamies, Oscar
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supporting information
p. 9036 - 9040
(2020/11/30)
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- Asymmetric δ-Lactam Synthesis with a Monomeric Streptavidin Artificial Metalloenzyme
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Reliable design of artificial metalloenzymes (ArMs) to access transformations not observed in nature remains a long-standing and important challenge. We report that a monomeric streptavidin (mSav) Rh(III) ArM permits asymmetric synthesis of α,β-unsaturated-δ-lactams via a tandem C-H activation and [4+2] annulation reaction. These products are readily derivatized to enantioenriched piperidines, the most common N-heterocycle found in FDA approved pharmaceuticals. Desired δ-lactams are achieved in yields as high as 99% and enantiomeric excess of 97% under aqueous conditions at room temperature. Embedding a Rh cyclopentadienyl (Cp?) catalyst in the active site of mSav results in improved stereocontrol and a 7-fold enhancement in reactivity relative to the isolated biotinylated Rh(III) cofactor. In addition, mSav-Rh outperforms its well-established tetrameric forms, displaying 11-33 times more reactivity.
- Hassan, Isra S.,Ta, Angeline N.,Danneman, Michael W.,Semakul, Natthawat,Burns, Matthew,Basch, Corey H.,Dippon, Vanessa N.,McNaughton, Brian R.,Rovis, Tomislav
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supporting information
p. 4815 - 4819
(2019/03/26)
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- Polymerizable compound, preparation method thereof and display device
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The invention provides a polymerizable compound, a preparation method thereof and a display device and relates to the field of liquid crystal display. The polymerizable compound is suitable for use asa reactive mesocrystal and is used for increasing the response speed of a liquid crystal molecule in a liquid crystal medium in which a polymer is stably oriented. The polymerizable compound has a structural general formula as shown in the specification. The invention relates to an application of the polymerizable compound to the liquid crystal medium.
- -
-
Paragraph 0087; 0091; 0103; 0133; 0154
(2018/06/26)
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- Macrolide Synthesis through Intramolecular Oxidative Cross-Coupling of Alkenes
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A RhIII-catalyzed intramolecular oxidative cross-coupling between double bonds for the synthesis of macrolides is described. Under the optimized reaction conditions, macrocycles containing a diene moiety can be formed in reasonable yields and with excellent chemo- and stereoselectivity. This method provides an efficient approach to synthesize macrocyclic compounds containing a 1,3-conjugated diene structure.
- Jiang, Bing,Zhao, Meng,Li, Shu-Sen,Xu, Yun-He,Loh, Teck-Peng
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supporting information
p. 555 - 559
(2018/02/21)
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- Design, synthesis, antiproliferative activity and docking studies of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline as potential EGFR inhibitors
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Eight series of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, MCF-7 and PC-3). Most of the forty nine target compounds showed excellent antiproliferative activity against one or several cancer cell lines. The compound 13a showed the best activity against A549, MCF-7 and PC-3 cancer cell lines, with the IC50 values of 1.09 ± 0.04 μM, 1.34 ± 0.13 μM and 1.23 ± 0.09 μM, respectively. Eight selected compounds were further selected to evaluated for the inhibitory activity against EGFR kinase. Three of them showed equal activity against EGFR kinase to positive control afatinib. AnnexinV-FITC, propidium iodide (PI) double staining and acridine orange single staining results indicated that the compound 13a could induce apoptosis of human lung cancer A549 cells.
- OuYang, Yiqiang,Zou, Wensheng,Peng, Liang,Yang, Zunhua,Tang, Qidong,Chen, Mengzi,Jia, Shuang,Zhang, Hong,Lan, Zhou,Zheng, Pengwu,Zhu, Wufu
-
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- Synthetic method and application of azaspirocyclohexadienone
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The invention discloses a method of synthesizing aryl substituted azaspirocyclohexadienone by aromatizing a visible light induced (N)-benzylacrylamide compound and diazonium salt of fluoboric acid toform a ring. The synthesized target compound has the structure as shown in the formula as described in the specification. A preparation method comprises the following steps: carrying out a reaction bytaking the (N)-benzylacrylamide compound and the diazonium salt as a reaction primer for 18 h, Ru(bpy)3Cl2 as a catalyst, K2CO3 as alkali and DMF (N,N-dimethylformamide) as a solvent in a nitrogen environment, wherein the reaction temperature is room temperature; and carrying out column chromatography or thin-layer chromatographic separation and purification on the product through washing, concentration and the like to obtain the target product azaspirocyclohexadienone. The synthesizing reaction is simple to operate, the adopted free radical source is low in price and easy to obtain, the reaction system is mild and environmentally friendly, and the method is high in selectivity, simple in condition and high in yield, and has a huge popularization and application value.
- -
-
Paragraph 0009; 0010; 0011
(2018/08/04)
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- Ni-Catalyzed Enantioselective Reductive Diarylation of Activated Alkenes by Domino Cyclization/Cross-Coupling
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A Ni-catalyzed enantioselective reductive diarylation of activated alkenes by domino cyclizative/cross-coupling of two aryl bromides is developed. This reaction proceeds under very mild conditions and shows broad substrate scope, without requiring the use of preformed organometallic reagents. Moreover, this approach provides direct access to various bis-heterocycles bearing all-carbon quaternary centers in synthetically useful yields (up to 81%) with excellent enantioselectivity (>30 examples, 90-99% ee).
- Wang, Kuai,DIng, Zhengtian,Zhou, Zhijun,Kong, Wangqing
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supporting information
p. 12364 - 12368
(2018/10/05)
-
- Production method of trifluoroethyl methacrylate
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The invention relates to the technical field of chemical synthesis and particularly relates to a production method of trifluoroethyl methacrylate. The production method comprises the following steps of: (1) preparation of methylpropenoyl chloride: adding triethylamine hydrochloride and a polymerization inhibitor into methacrylic acid, adding solid phosgene in 1 hour at a room temperature, reactingfor 5-8 hours at a temperature of 30-70 DEG C, distilling at a normal pressure, collecting fractions with the temperature of 95-98 DEG C to obtain methylpropenoyl chloride, wherein the mass ratio ofthe solid phosgene to methacrylic acid is 1:0.5; (2) preparation of trifluoroethyl methacrylate: leading trifluoroethanol, methylpropenoyl chloride and the polymerization inhibitor for 8-12 hours at the temperature of 40-75 DEG C, then collecting a target product of trifluoroethyl methacrylate from reaction products. The production method has the advantages of mild condition in the reaction process, stable product quality and cost reduction, and is suitable for industrial production.
- -
-
Paragraph 0015; 0017; 0019
(2018/12/02)
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- Copper-Promoted Thiolation of C(sp2)–H Bonds Using a 2-Amino Alkylbenzimidazole Directing Group
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A copper-promoted thiolation of C(sp2)–H bonds with disulfides was achieved by using 2-amino alkylbenzimidazole (MBIP amine) as a new and removable N,N-bidentate directing group. This strategy gives a variety of functionalized thioethers in moderate to excellent yields in a simple and efficient way. Importantly, the substrate scope is not limited to aromatic amides; diverse alkenyl amides are also compatible. Furthermore, this synthetic approach provides a potentially feasible way to achieve structural modification of related benzimidazole-containing compounds through direct C–H activation.
- Liu, Shuang-Liang,Li, Xue-Hong,Shi, Tan-Hao,Yang, Guang-Chao,Wang, Hai-Li,Gong, Jun-Fang,Song, Mao-Ping
-
supporting information
p. 2280 - 2289
(2017/05/01)
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- General C-H Arylation Strategy for the Synthesis of Tunable Visible Light-Emitting Benzo[a]imidazo[2,1,5-c,d]indolizine Fluorophores
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Herein we report the discovery of the benzo[a]imidazo[2,1,5-c,d]indolizine motif displaying tunable emission covering most of the visible spectrum. The polycyclic core is obtained from readily available amides via a chemoselective process involving Tf2O-mediated amide cyclodehydration, followed by intramolecular C-H arylation. Additionally, these fluorescent heterocycles are easily functionalized using electrophilic reagents, enabling divergent access to varied substitution. The effects of said substitution on the compounds' photophysical properties were rationalized by density functional theory calculations. For some compounds, emission wavelengths are directly correlated to the substituent's Hammett constants. Easily introduced nonconjugated reactive functional groups allow the labeling of biomolecules without modification of emissive properties. This work provides a straightforward platform for the synthesis of new moderately bright fluorescent dyes remarkable for their chemical stability, predictability, and unusually high excitation-emission differential.
- Lévesque, éric,Bechara, William S.,Constantineau-Forget, Léa,Pelletier, Guillaume,Rachel, Natalie M.,Pelletier, Joelle N.,Charette, André B.
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p. 5046 - 5067
(2017/05/24)
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- C-H and N-H Bond Annulation of Benzamides with Isonitriles Catalyzed by Cobalt(III)
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A simple efficient, atom-economical procedure was developed for the cobalt-catalyzed C-H bond annulation of benzamides with isonitriles under mild conditions. The reaction tolerates a variety of functional group including heterocycles. Diverse 3-(alkylimino)-2-quinolin-8-yl-2,3-dihydro-1 H -isoindol-1-ones were synthesized using isonitriles as the C1 source through C-H and N-H bond annulation via C-H bond activation in a 'green' solvent. Vinylamides were also used similarly with tert -butyl isonitrile to give 3-(tert -butylimino)-1-quinolin-8-yl-1 H -pyrrol-2(5 H)-ones.
- Kalsi, Deepti,Barsu, Nagaraju,Dahiya, Pardeep,Sundararaju, Basker
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supporting information
p. 3937 - 3944
(2017/08/29)
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- Transformable Sulfoximine Assisted One-Pot Double Annulation of Vinylic C-H Bonds with Unactivated Alkynes
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The methylphenyl sulfoximine (MPS) directing group (DG) successfully promotes the one-pot double annulation of acrylic acids with alkynes under Ru catalysis, which is unprecedented. Diverse arrays of pyrido-fused-isoquinolinone skeletons are fabricated from acrylamides, creating two C-C and two C-N bonds in a single operation. The unsymmetrical annulation with two distinct alkynes is presented. The recovery of methylphenyl sulfoxide, a precursor of MPS, validates the synthetic adaptability of transformable-DG (TfDG) in C-H activation.
- Shankar, Majji,Guntreddi, Tirumaleswararao,Ramesh,Sahoo, Akhila K.
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supporting information
p. 5665 - 5668
(2017/10/25)
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- An amphiphilic and photoswitchable organocatalyst for the aldol reaction based on a product-imprinted polymer
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A series of amphiphilic molecularly imprinted polymers (MIP1, MIP2, MIP3, MIP4, MIP5, and MIP6) containing hydrophobic photoresponsive sites and hydrophilic catalytically active sites were fabricated using bifunctional monomers. These polymers were characterized by scanning electron microscopy, N2 adsorption–desorption analysis, Fourier Transform infrared spectroscopy, thermal gravimetric analysis, and ultraviolet–visible spectroscopy. The catalytic activity of the amphiphilic molecularly imprinted polymer was investigated towards the aldol reaction between p-nitroaldehyde and acetone (a molecular enlargement reaction) in a mixed solvent of DMSO and water at room temperature. The polymer catalyst MIP3 performs best, and displayed good conversions with low catalyst loading (5 mol% of L-hydroxyproline with respect to the aldehyde) and photoswitching properties (photo-regulated conversion difference of 20%). Compared with the corresponding non-imprinted polymer, a higher binding capacity, higher conversion, and better photoswitching properties were obtained when the molecularly imprinted polymer was used as the catalyst, illustrating the importance of the specific cavities in the molecularly imprinted polymer.
- Zheng, An-xun,Gong, Cheng-bin,Zhang, Wei-jing,Tang, Qian,Huang, Hai-rong,Chow, Cheuk-fai,Tang, Qian
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p. 115 - 125
(2017/10/30)
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- Expedient Iron-Catalyzed C-H Allylation/Alkylation by Triazole Assistance with Ample Scope
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Triazole assistance set the stage for a unified strategy for the iron-catalyzed C-H allylation of arenes, heteroarenes, and alkenes with ample scope. The versatile catalyst also proved competent for site-selective methylation, benzylation, and alkylation with challenging primary and secondary halides. Triazole-assisted C-H activation proceeded chemo-, site-, and diastereo-selectively, and the modular TAM directing group was readily removed in a traceless fashion under exceedingly mild reaction conditions. One for all: A unified strategy for iron-catalyzed C-H allylation and alkylation was developed by the use of a triazole directing group that could be cleaved under exceedingly mild conditions.
- Cera, Gianpiero,Haven, Tobias,Ackermann, Lutz
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supporting information
p. 1484 - 1488
(2016/02/12)
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- RhIII-Catalyzed C-H Allylation of Amides and Domino Cycling Synthesis of 3,4-Dihydroisoquinolin-1(2H)-ones with N-Bromosuccinimide
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A RhIII-catalyzed C-H allylation of electron-deficient arenes, heteroarenes, and alkenes at room temperature was developed with allyl bromide. The reaction was carried out in diethyl ether without dehydration, and C-H activation was assisted by the directing anionic nitrogen of the aniline-derived amide. Following the allylation, a domino cycling synthesis of 3,4-dihydroisoquinolin-1(2H)-ones with N-bromosuccinimide (NBS) through intramolecular aminobromination of the introduced double bond was achieved. A C-H allylation of amides with allyl halides at room temperature and a tandem synthesis of 3,4-dihydroisoquinolin-1(2H)-ones with N-bromosuccinimide (NBS) are reported.
- Dai, Huimin,Yu, Chao,Lu, Changsheng,Yan, Hong
-
supporting information
p. 1255 - 1259
(2016/03/16)
-
- Enantioselective Total Syntheses of (R)- A nd (S)-Naphthotectone, and Stereochemical Assignment of the Natural Product
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Both isomers of naphthotectone, an isoprenoid quinone from Verbenaceae Tectona grandis possessing interesting biological activities, were enantioselectively obtained by two different synthetic routes in which the carbon side-chain of the naphthoquinone core was introduced using either a Sonogashira or a Heck coupling reaction. In both cases, the naphthoquinone core of the final products was obtained by a late-stage anodic treatment. (R)-Naphthotectone was obtained in six steps from leuconaphthazarin with an overall yield of 38 % and an enantiomeric excess of 86 %. This compound was found to have the same absolute configuration as the natural product at its C-3′ stereogenic center. (S)-Naphthotectone was obtained in five steps from leuconaphthazarin with an overall yield of 36 % and an enantiomeric excess of 80 %. Naphthotectone was synthesized in both racemic and enantioenriched forms by two different synthetic strategies using Pd coupling reactions and anodic treatment as key steps. The stereochemistry of the natural product has been assigned.
- Guerrero-Vásquez, Guillermo A.,Galarza, Flávia A. D.,Molinillo, José M. G.,Andrade, Carlos Kleber Z.,Macías, Francisco A.
-
supporting information
p. 1599 - 1604
(2016/04/05)
-
- High-valent palladium-promoted formal Wagner-Meerwein rearrangement
-
An oxy-palladation, formal Wagner-Meerwein rearrangement and fluorination cascade has been established for generating fluorinated oxazolidine-2,4-diones and oxazolidin-2-ones. The reaction has a broad substrate scope in which both aryl and alkyl groups can be utilized as efficient migrating groups. Experimental evidence suggests that the reaction is initiated by anti-oxy-palladation of the olefin, followed by oxidative generation of an alkyl PdIV intermediate and a concerted migration-fluorination.
- Wu, Hongmiao,Yang, Bin,Zhu, Lin,Lu, Ronghua,Li, Guigen,Lu, Hongjian
-
supporting information
p. 5804 - 5807
(2016/11/29)
-
- Regiocontrolled Coupling of Aromatic and Vinylic Amides with α-Allenols to Form γ-Lactams via Rhodium(III)-Catalyzed C-H Activation
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A mild, regiocontrolled coupling of aromatic and vinylic amides with α-allenols to form γ-lactams via rhodium(III)-catalyzed C-H activation has been demonstrated. This [4 + 1] annulation reaction provides an efficient method for the synthesis of isoindolinones and 1,5-dihydro-pyrrol-2-ones bearing a tetrasubstituted carbon atom α to the nitrogen atom with good functional group tolerance. The hydroxyl group in the allene substrate is essential in controlling the chemo- and regioselectivity of the reaction probably by coordination interaction with the rhodium catalyst.
- Zhou, Zhi,Liu, Guixia,Lu, Xiyan
-
supporting information
p. 5668 - 5671
(2016/11/17)
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- Safe, selective, and high-yielding synthesis of acryloyl chloride in a continuous-flow system
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Acid chlorides are an important class of compounds and their high reactivity and instability has prompted us to develop a straightforward procedure for their synthesis with ondemand and on-site synthesis possibilities. The focus of this report is acryloyl chloride, mainly important for the acrylate and polymer industry. A continuous-flow methodology was developed for the fast and selective synthesis of the otherwise highly unstable acryloyl chloride. Three routes were investigated in a microreactor setup and all three can potentially be used for its production. The methodology was further expanded to the synthesis of other unstable acid chlorides by both the thionyl chloride and the oxalyl chloride mediated processes. The most sustainable method was the oxalyl chloride mediated procedure under solvent-free conditions, in which nearequimolar amounts of carboxylic acid and oxalyl chloride were used in the presence of catalytic amounts of DMF at room temperature. Within 1 to 3 min, nearly full conversions into the acid chlorides were achieved.
- Movsisyan, Marine,Heugebaert, Thomas S. A.,Dams, Rudy,Stevens, Christian V.
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p. 1945 - 1952
(2018/08/17)
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- Asymmetric dihydroxylation of esters and amides of methacrylic, tiglic, and angelic acid: No exception to the sharpless mnemonic!
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Literature findings on the facial selectivity of the Sharpless asymmetric dihydroxylation (SAD) of isobutyl angelate are contradictory and partly in conflict with the Sharpless mnemonic. We systematically screened the SAD of esters and amides of angelic, tiglic, and methacrylic acid. Enantiocontrol arose in 14 of the 15 reactions, culminating at 99 % ee for the Weinreb amide of tiglic acid. The absolute configurations of all the nonracemic products were established by (stereo)chemical correlations. Without exception, they conform to the Sharpless mnemonic.
- Weber, Fabian,Brückner, Reinhard
-
supporting information
p. 2428 - 2449
(2015/04/22)
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- High purity production of methacrylic acid chloride
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PROBLEM TO BE SOLVED: To provide a method for increasing the productivity of high-purity methacrylic acid chloride of an industrially useful compound by reducing the influence of the polymerization loss of a raw material, and effectively subjecting the raw material to a desired reaction without requiring a raw material that forms impurities whose separation is difficult and is difficult to treat. SOLUTION: The method for producing the methacrylic acid chloride includes reacting an aromatic acid chloride [molar amount: A] represented by general formula (1) (wherein, X is hydrogen, chlorine or methyl; and n is an integer of 0-2) with methacrylic acid [molar amount: B] represented by general formula (2) in a molar ratio [A/B] of 1.2-1.65 when producing the methacrylic acid chloride represented by formula (3) by reacting the aromatic acid chloride represented by formula (1) with the methacrylic acid represented by formula (2). COPYRIGHT: (C)2012,JPO&INPIT
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Paragraph 0018; 0019
(2016/12/12)
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- Rhodium(iii)-catalyzed C-H/C-C activation sequence: Vinylcyclopropanes as versatile synthons in direct C-H allylation reactions
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Succession of C-H activation and C-C activation was achieved by using a single rhodium(iii) catalyst. Vinylcyclopropanes were used as versatile coupling partners. Mechanistic studies suggest that the olefin insertion step is rate-determining and a facile β-carbon elimination is involved, which represents a novel ring opening mode of vinylcyclopropanes. This journal is
- Wu, Jia-Qiang,Qiu, Zhi-Ping,Zhang, Shang-Shi,Liu, Jing-Gong,Lao, Ye-Xing,Gu, Lian-Quan,Huang, Zhi-Shu,Li, Juan,Wang, Honggen
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supporting information
p. 77 - 80
(2015/01/09)
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- Direct ortho-thiolation of arenes and alkenes by nickel catalysis
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The direct thiolation of arenes and alkenes with diaryl disulfides was developed by nickel catalysis. The reaction displayed exceptional compatibility with a wide range of functional groups to regioselectively give the diaryl sulfides and alkenyl sulfides in high yields.
- Lin, Cong,Li, Danyang,Wang, Binjie,Yao, Jinzhong,Zhang, Yuhong
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supporting information
p. 1328 - 1331
(2015/03/14)
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- The role of phosphate in a multistep enzymatic reaction: Reactions of the substrate and intermediate in pieces
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Several mechanistically unrelated enzymes utilize the binding energy of their substrate's nonreacting phosphoryl group to accelerate catalysis. Evidence for the involvement of the phosphodianion in transition state formation has come from reactions of the substrate in pieces, in which reaction of a truncated substrate lacking its phosphorylmethyl group is activated by inorganic phosphite. What has remained unknown until now is how the phosphodianion group influences the reaction energetics at different points along the reaction coordinate. 1-Deoxy-d-xylulose-5-phosphate (DXP) reductoisomerase (DXR), which catalyzes the isomerization of DXP to 2-C-methyl-d-erythrose 4-phosphate (MEsP) and subsequent NADPH-dependent reduction, presents a unique opportunity to address this concern. Previously, we have reported the effect of covalently linked phosphate on the energetics of DXP turnover. Through the use of chemically synthesized MEsP and its phosphate-truncated analogue, 2-C-methyl-d-glyceraldehyde, the current study revealed a loss of 6.1 kcal/mol of kinetic barrier stabilization upon truncation, of which 4.4 kcal/mol was regained in the presence of phosphite dianion. The activating effect of phosphite was accompanied by apparent tightening of its interactions within the active site at the intermediate stage of the reaction, suggesting a role of the phosphodianion in disfavoring intermediate release and in modulation of the on-enzyme isomerization equilibrium. The results of kinetic isotope effect and structural studies indicate rate limitation by physical steps when the covalent linkage is severed. These striking differences in the energetics of the natural reaction and the reactions in pieces provide a deeper insight into the contribution of enzyme-phosphodianion interactions to the reaction coordinate.
- Kholodar, Svetlana A.,Allen, C. Leigh,Gulick, Andrew M.,Murkin, Andrew S.
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p. 2748 - 2756
(2015/03/04)
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- Palladium-catalyzed picolinamide-directed coupling of C(sp2)-H and C(sp2)-H: A straightforward approach to quinolinone and pyridone scaffolds
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An unprecedented palladium-catalyzed picolinamide-directed coupling of C(sp2)-H and C(sp2)-H has been developed with exclusive formation of the six-membered ring heterocyclics-quinolinone and pyridone. The method employs cyclic hypervalent iodine as oxidant and features good functional-group tolerance. Another advantage of this reaction is that sequential C-H/C-H and C-H/N-H coupling could be achieved. This journal is
- Zhang, Dengyou,Gao, Feng,Nian, Yong,Zhou, Yu,Jiang, Hualiang,Liu, Hong
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supporting information
p. 7509 - 7511
(2015/05/04)
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- Domino Heck/borylation sequence towards indolinone-3-methyl boronic esters: trapping of the σ-alkylpalladium intermediate with boron
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Pd-catalyzed domino Heck/borylation of acrylamides with B2pin2 is reported to generate synthetically useful indolinone-3-methyl boronic esters, via capturing σ-alkyl palladium with boron. Further functionalization of the obtained boronic ester qualify it as a new starting point for the functionalization of specific C(sp3)-H bond. Moreover, the application of an Ugi-adduct as starting material or B2nep2 as an alternative boron source works equally well, making this a broadly applicable and robust method for the formation of a C-C and C-B bond in a single operation.
- Vachhani, Dipak D.,Butani, Himanshu H.,Sharma, Nandini,Bhoya, Umed C.,Shah, Anamik K.,Van Der Eycken, Erik V.
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supporting information
p. 14862 - 14865
(2015/10/06)
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- An LC-MS/MS method to quantify acylcarnitine species including isomeric and odd-numbered forms in plasma and tissues
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Acylcarnitines are intermediates of fatty acid and amino acid oxidation found in tissues and body fluids. They are important diagnostic markers for inherited diseases of peroxisomal and mitochondrial oxidation processes and were recently described as biomarkers of complex diseases like the metabolic syndrome. Quantification of acylcarnitine species can become challenging because various species occur as isomers and/or have very low concentrations. Here we describe a new LC-MS/MS method for quantification of 56 acylcarnitine species with acyl-chain lengths from C2 to C18. Our method includes amino acid-derived positional isomers, like methacrylyl-carnitine (2-M-C3:1-CN) and crotonyl-carnitine (C4:1-CN), and odd-numbered carbon species, like pentadecanoyl-carnitine (C15:0-CN) and heptadecanoyl-carnitine (C17:0-CN), occurring at very low concentrations in plasma and tissues. Method validation in plasma and liver samples showed high sensitivity and excellent accuracy and precision. In an application to samples from streptozotocin-treated diabetic mice, we identified significantly increased concentrations of acylcarnitines derived from branched-chain amino acid degradation and of odd-numbered straight-chain species, recently proposed as potential biomarkers for the metabolic syndrome. In conclusion, the LC-MS/MS method presented here allows robust quantification of isomeric acylcarnitine species and extends the palette of acylcarnitines with diagnostic potential derived from fatty acid and amino acid metabolism.
- Giesbertz, Pieter,Ecker, Josef,Haag, Alexander,Spanier, Britta,Daniel, Hannelore
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p. 2029 - 2039
(2015/11/17)
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- Polymerizable mesogen compound having improved photoreactive efficiency and polymerizable liquid crystal compositions containing the same
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The present invention relates to a polymerizable mesogen compound having improved photo-reaction efficiency by introducing an alpha-thiomethyl acrylate group as a photo-reactive group, and to a polymerizable liquid crystal composition containing the same. The polymerizable mesogen compound of the present invention has improved photo-reaction efficiency at a relatively low energy state by introducing an alpha-thiomethyl acrylate group as a photo-reactive group, retains excellent solubility in a host liquid crystal due to an asymmetric structure thereof, and improves stability of the pretilt angle after photo-crosslinking, and thus can be useful as a polymerizable liquid crystal composition, particularly, a polymerizable liquid crystal composition for a polymer stabilization alignment type liquid crystal display.
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Paragraph 0129-0131
(2016/12/26)
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- Methacryloyl chloride dimers: From structure elucidation to a manifold of chemical transformations
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We report the isolation and elucidation of structure, formation mechanisms, and reactivity of elusive methacryloyl chloride dimers. Upon standing of a sample of methacryloyl chloride (1) for prolonged periods of time dimer 3 forms via oxa-Diels-Alder reaction even at low temperatures. If traces of a Lewis acid are present, dimer 3 isomerizes into a mixture of 2-oxo-cyclopentanecarbonyl chlorides 4, 14, and traces of 5, with a relative ratio that depends on the nature of the Lewis acid and reaction time. Dimer 3 can also be separated and isolated by vacuum distillation and selectively converted into derivatives of 2,5-dimethyl-2-hydroxyadipic acid, as well as into the compound 14 by treating with a catalytic amount of titanium tetrachloride. Additionally, based on the study, suggestions on purification and handling of methacryloyl chloride are proposed.
- Warneke, Jonas,Wang, Ziyan,Zeller, Matthias,Leibfritz, Dieter,Plaumann, Markus,Azov, Vladimir A.
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p. 6515 - 6521
(2015/03/30)
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- Phenylboronate-diol crosslinked glycopolymeric nanocarriers for insulin delivery at physiological pH
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Research into polymers with glucose-sensitivity in physiological conditions has expanded recently due to their therapeutic potential in diabetes. Herein, to explore the glucose-responsive properties of a new polymer under physiological conditions, we synthesized an amphiphilic block glycopolymer based on phenylboronic acid and a carbohydrate, which was named poly(d- gluconamidoethyl methacrylate-block-3-acrylamidophenylboronic acid) (p(AAPBA-b-GAMA)). Based on the cross-linking between the diol groups of the carbohydrates and phenylboronic acid, the glycopolymers self-assembled to form nanoparticles (NPs). The glucose-sensitivity was revealed by the swelling behavior of the NPs at different glucose concentrations and was found to be dependent on the glucose level. The morphology of the NPs revealed by transmission electron microscopy showed that the NPs were spherical in shape with good dispersity. The cell viability of the NPs investigated by MTT assay was more than 90%, indicating that the glycopolymers had good cytocompatibility. Insulin could be loaded onto the glycopolymer NPs with high efficiency (up to 10%), and insulin release increased with enhancement of the glucose level in the medium. Such a glucose-responsive glycopolymer is an excellent candidate that holds great potential in the treatment of diabetes.
- Guo, Qianqian,Wu, Zhongming,Zhang, Xinge,Sun, Lei,Li, Chaoxing
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p. 911 - 920
(2014/02/14)
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- 1-(2-hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile derivatives as potent and tissue selective androgen receptor modulators
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We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.
- Chekler, Eugene L. Piatnitski,Unwalla, Rayomond,Khan, Taukeer A.,Tangirala, Raghuram S.,Johnson, Mark,St. Andre, Michael,Anderson, James T.,Kenney, Thomas,Chiparri, Sue,McNally, Chris,Kilbourne, Edward,Thompson, Catherine,Nagpal, Sunil,Weber, Gregory,Schelling, Scott,Owens, Jane,Morris, Carl A.,Powell, Dennis,Verhoest, Patrick R.,Gilbert, Adam M.
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supporting information
p. 2462 - 2471
(2014/04/17)
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- Discovery of imigliptin, a novel selective DPP-4 inhibitor for the treatment of type 2 diabetes
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We report our discovery of a novel series of potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors. Starting from a lead identified by scaffold-hopping approach, our discovery and development efforts were focused on exploring structure-activity relationships, optimizing pharmacokinetic profile, improving in vitro and in vivo efficacy, and evaluating safety profile. The selected candidate, Imigliptin, is now undergoing clinical trial.
- Shu, Chutian,Ge, Hu,Song, Michael,Chen, Jyun-Hong,Zhou, Huimin,Qi, Qu,Wang, Feng,Ma, Xifeng,Yang, Xiaolei,Zhang, Genyan,Ding, Yanwei,Zhou, Dapeng,Peng, Peng,Shih, Cheng-Kon,Xu, Jun,Wu, Frank
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supporting information
p. 921 - 926
(2014/09/17)
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- Mild rhodium(III)-catalyzed C-H allylation with 4-vinyl-1,3-dioxolan-2-ones: Direct and stereoselective synthesis of (E)-allylic alcohols
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A rhodium(III)-catalyzed C-H direct allylation reaction with 4-vinyl-1,3-dioxolan-2-ones has been developed. The reaction provides a facile and stereoselective access to substituted-(E)-allylic alcohols under mild and redox-neutral reaction conditions. Olefinic C-H activation is applicable, giving multifunctionalized skipped dienes in good yields. Minimal double-bond migration was observed.
- Zhang, Shang-Shi,Wu, Jia-Qiang,Lao, Ye-Xing,Liu, Xu-Ge,Liu, Yao,Lv, Wen-Xin,Tan, Dong-Hang,Zeng, Yao-Fu,Wang, Honggen
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supporting information
p. 6412 - 6415
(2015/01/09)
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- Ligand-promoted alkylation of C(sp3)-H and C(sp2)-H bonds
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9-Methylacridine was identified as a generally effective ligand to promote a Pd(II)-catalyzed C(sp3) - H and C(sp2) - H alkylation of simple amides with various alkyl iodides. This alkylation reaction was applied to the preparation of unnatural amino acids and geometrically controlled tri- and tetrasubstituted acrylic acids.
- Zhu, Ru-Yi,He, Jian,Wang, Xiao-Chen,Yu, Jin-Quan
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supporting information
p. 13194 - 13197
(2015/03/30)
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- Rh(III)-catalyzed halogenation of vinylic C-H bonds: Rapid and general access to Z-halo acrylamides
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Herein, the regio- and stereoselective iodination, along with some examples for the bromination, of readily available acrylamides to access a variety of differently substituted Z-haloacrylic acid derivatives is reported. The reaction proceeds under mild conditions via a Rh(III)-catalyzed C-H-activation/ halogenation mechanism and represents a rare example of a direct halogenation of electron-poor acrylic acid derivatives.
- Kuhl, Nadine,Schroeder, Nils,Glorius, Frank
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supporting information
p. 3860 - 3863
(2013/09/02)
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- Ir(III)-catalyzed mild C-H amidation of arenes and alkenes: An efficient usage of acyl azides as the nitrogen source
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Reported herein is the development of the Ir(III)-catalyzed direct C-H amidation of arenes and alkenes using acyl azides as the nitrogen source. This procedure utilizes an in situ generated cationic half-sandwich iridium complex as a catalyst. The reaction takes place under very mild conditions, and a broad range of sp2 C-H bonds of chelate group-containing arenes and olefins are smoothly amidated with acyl azides without the intervention of the Curtius rearrangement. Significantly, a wide range of reactants of aryl-, aliphatic-, and olefinic acyl azides were all efficiently amidated with high functional group tolerance. Using the developed approach, Z-enamides were readily accessed with a complete control of regio- and stereoselectivity. The developed direct amidation proceeds in the absence of external oxidants and releases molecular nitrogen as a single byproduct, thus offering an environmentally benign process with wide potential applications in organic synthesis and medicinal chemistry.
- Ryu, Jaeyune,Kwak, Jaesung,Shin, Kwangmin,Lee, Donggun,Chang, Sukbok
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supporting information
p. 12861 - 12868
(2013/09/23)
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- PROCESS FOR THE PREPARATION OF MUSCARINIC RECEPTOR ANTAGONIST
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The present invention relates to novel and improved processes for the preparation of (r)-2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenylisobutyrate represented by the following structural formula-1 and its pharmaceutically acceptable salts thereof.
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Page/Page column 60
(2012/08/07)
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