- Two-dimensional (2d) correlation analysis and the search for intermediates: A strictly mathematical approach to an important mechanistic question
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In situ spectroscopic studies of metal-mediated syntheses of new and previously unstudied systems are being increasingly used to better understand speciation and mechanistic aspects. These types of experiments give rise to an interesting question: namely, can one deduce from in situ data alone, and with no a priori chemical knowledge (i.e. chemical assignments), which pure component spectral estimates correspond to intermediates? In the present contribution, a statistical 2D correlation analysis is introduced to solve this problem for unicyclic catalytic systems. Such a methodological development achieves two goals: (1) it allows the experimentalist to concentrate on the most meaningful information at the outset of a new exploratory study (focus on the species directly associated with the catalysis), and (2) it helps to free the experimentalist from chemical bias and prejudice, i.e. believing that a specific organometallic species has to be an intermediate due to one or more chemical arguments, when in fact it may be just a side product or spectator species in the metal-mediated synthesis. The 2D correlation analysis is first tested with a numerically simulated data set and then with a real in situ FTIR data set from an unmodified rhodium-catalyzed hydroformylation. The resulting statistical 2D correlation analysis provides a clear and correct answer.
- Xu, Qisong,Guo, Liangfeng,Dinh, Tung Nguyen,Cheong, Angie,Garland, Marc
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- Synchronicity of mononuclear and dinuclear events in homogeneous catalysis. Hydroformylation of cyclopentene using Rh4(CO)12 and HRe(CO)5 as precursors
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The combined application of two or more metals in homogeneous catalysis can lead to synergistic effects; however, the phenomenological basis for these observations often goes undetermined. The heterobimetallic catalytic binuclear elimination reaction, a system involving both mononuclear and dinuclear intermediates, has been repeatedly suggested as a possible mechanism. In the present contribution, the simultaneous application of Rh4(CO) 12 and HRe(CO)5 as precursors in the hydroformylation reaction leads to a very strong synergistic rate effect. In situ spectroscopic measurements confirm the presence of both mononuclear and dinuclear intermediates such as RCORh(CO)4 and RhRe(CO)9 in the active system. Moreover, kinetic analysis confirms interconversion of these intermediates as well as their statistical correlation with organic product formation. Specifically, the rate of hydrogen activation by RhRe(CO)9 is exactly equal to the rate of aldehyde formation from binuclear elimination between HRe(CO)5 and RCORh-(CO)4 at all reaction conditions studied. Thus the catalytic events involving mononuclear species and those involving dinuclear species are synchronized. In the present experiments, the new topology is orders of magnitude more efficient than the corresponding unicyclic rhodium system.
- Li, Chuanzhao,Chen, Li,Garland, Marc
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- Concurrent synergism and inhibition in bimetallic catalysis: Catalytic binuclear elimination, solute-solute interactions and a hetero-bimetallic hydrogen-bonded complex in Rh-Mo hydroformylations
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Hydroformylations of cyclopentene and 3,3-dimethylbut-1-ene were performed using both Rh4(CO)12 and (η5-C 5H5)Mo(CO)3H as precursors in n-hexane at 298 K. Both stoichiometric and catalytic hydroformylations were conducted as well as isotopic labeling experiments. Six organometallic pure component spectra were recovered from the high-pressure FTIR experiments, namely the known species Rh4(CO)12, (η5-C5H 5)Mo(CO)3H, RCORh(CO)4, and the new heterobimetallic complexes RhMo(CO)7(η5-C 5H5), a weak hydrogen bonded species (η5- C5H5)Mo(CO)3H-C5H 9CORh(CO)4, and a substituted RhMo(CO) 7-y(η5-C5H5)Ly, where y = 1 or 2 and L = (--C5H8). The main findings were (1) catalytic binuclear elimination (CBER) occurs between (η5-C 5H5)Mo(CO)3H and RCORh(CO)4 resulting in aldehyde and RhMo(CO)7(η5-C 5H5), and this mechanism is responsible for ca. 10% of the product formation; (2) molecular hydrogen is readily activated by the new heterobimetallic complex(es); (3) FTIR and DFT spectroscopic evidence suggests that the weak hydrogen bonded species (η5-C5H 5)Mo(CO)3H-C5H9CORh(CO)4 has an interaction of the type η5-C5H4-HO - C; and (4) independent physicochemical experiments for volumes of interaction confirm that significant solute-solute interactions are present. With respect to the efficiency of the catalytic cycle, the formation of a weak (η5-C5H5)Mo(CO)3H-C 5H9CORh(CO)4 complex results in a significant decrease in the measured turnover frequency (TOF) and is the primary reason for the inhibition observed in the bimetallic catalytic hydroformylation. Such hydrogen bonding through the η5-C5H5 ring might have relevance to inhibition observed in other catalytic metallocene systems. The present catalytic system is an example of concurrent synergism and inhibition in bimetallic homogeneous catalysis.
- Li, Chuanzhao,Cheng, Shuying,Tjahjono, Martin,Schreyer, Martin,Garland, Marc
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- Highly efficient polymer-based nanoreactors for selective oxidation of alcohols in water
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In this study, we demonstrate the fabrication of thermo-responsive polymer-based TEMPO nanoreactors and their application in the catalytic selective oxidation of alcohols as a highly efficient and recoverable catalyst in aqueous media. First, a diblock amphiphilic copolymer NHS-P(MMA25-b-OEGMA75) consisting of poly(methyl methacrylate) (PMMA) and poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA300) with a terminal N-hydroxysuccinimide (NHS) activated ester was synthesized utilizing reversible addition–fragmentation chain transfer polymerization (RAFT) techniques. Free radical 2,2,6,6,-tetramethyipiperidinooxy (TEMPO) was then introduced into the end of the copolymer based on activated ester functionalization to afford the temperature responsive polymer-supported catalyst TEMPO-P(MMA25-b-OEGMA75). Next, core-shell TEMPO nanoreactors were formed through self-assembly of the amphiphilic block polymers in deionized water. The morphology of the nanoreactors was well characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The nanoreactors were then successfully applied in the selective oxidative of alcohols in water. A variety of aldehydes and ketones were achieved in excellent yields and selectivities in high reaction rates with low catalyst loading. The high efficiency in catalysis of the nanoreactors may attributed to the ideal environment where enhancing the interactions between the catalyst and the alcohol substrate, mimicking the environment of enzymes. The thermo-responsive polymer-based nanoreactors could be conveniently recovered in the temperature above the LCST of the polymer after extraction of product from the reaction mixture. This strategy provides an effective and cleaner way for the selective oxidative of alcohols in organic synthesis and industrial application.
- Chen, Tao,Xu, Zhenkai,Zhou, Lei,Qiu, Jiaqi,Wang, Maolin,Wang, Jiping
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- Facile One-Pot Transformation of Primary Alcohols into 3-Aryl- and 3-Alkyl-isoxazoles and -pyrazoles
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Various primary alcohols were smoothly transformed into 3-aryl- and 3-alkylisoxazoles in good yields in one pot by successive treatment with PhI(OAc) 2 in the presence of TEMPO, NH 2 OH, and then NCS, followed by reaction with alkynes in the presence of Et 3 N. Similarly, various primary alcohols were smoothly transformed into 3-aryl- and 3-alkylpyrazoles in good yields in one pot by successive treatment with PhI(OAc) 2 in the presence of TEMPO, PhNHNH 2, and then NCS and decyl methyl sulfide, followed by reaction with alkynes in the presence of Et 3 N. Thus, both 3-aryl- and 3-alkylisoxazoles, and 3-aryl- and 3-alkylpyrazoles could be prepared from readily available primary alcohols in one pot under transition-metal-free conditions.
- Kobayashi, Eiji,Togo, Hideo
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p. 3723 - 3735
(2019/09/30)
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- Supported rhodium liquid metal catalysts for the hydroformylation of olefins
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The hydroformylation of olefins in supported room temperature liquid metals was developed, and the supported Rh liquid metal catalysts (Rh SLMCs) showed unprecedented activity and high selectivity for the hydroformylation of olefins to aldehydes. The turnover frequency is up to 7000?h?1, much higher than that of homogeneous RhCl3?+?3PPh3 catalyst. Moreover, the Rh SLMCs can be recovered conveniently without obvious deactivation, and the total turnover number is up to 250?000. The active Rh(I) catalyst formed in situ can be reduced back to Rh(0) by the free electrons in liquid metal when H2/CO gas is emitted, and thus Rh is not leaked into the organic solvent. Long-chain olefins, cycloolefins and styrenes were applied, and the corresponding aldehydes were obtained in good to excellent yields.
- Sun, Hao,Guo, Wanwan,Liu, Junmei,Feng, Zhipeng,Li, Ruyue,Zhou, Xuyang,Huang, Jun
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- Intermediate of JAK inhibitor, and preparation method thereof
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The present invention relates to a novel key intermediate of a JAK inhibitor ruxolitinib, and a preparation method thereof, wherein the chemical name of the intermediate is (R)-3-(4-boric acid-1H-pyrazole-1-yl)-3-cyclopentylpropionitrile. According to the present invention, the new ruxolitinib preparation route is provided, wherein each reaction of the route has the high yield, the total yield ofthe route is high, the purity of the obtained product is good, the post-treatment of the reaction is simple, and column chromatography is not required; by adopting the route, the required raw materials or catalysts and other materials are relatively easy to obtain; and compared to the method in the prior art, the method of the present invention is economical and is suitable for industrial production.
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Paragraph 0076; 0077
(2018/03/24)
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- Preparation methods of JAK inhibitor and salt thereof
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The present invention relates to preparation methods of a JAK inhibitor and a salt thereof. The preparation method comprises: (1) carrying out a Suzuki coupling reaction on (R)-3-(4-boronic acid-1H-pyrazol-1-yl)-3-cyclopentylpropionitrile and 6-halogen-5-(2-methoxyvinyl)pyrimidin-4-ylamine to generate (3R)-cyclopentyl-3-[4-(5-(2-methoxyvinyl)pyrimidin-4-ylamine)pyrazol-1-yl]propionitrile; and (2)carrying out a protection group removing and ring-closure reaction on the (3R)-cyclopentyl-3-[4-(5-(2-methoxyvinyl)pyrimidin-4-ylamine)pyrazol-1-yl]propionitrile to generate a JAK inhibitor ruxolitinib. According to the present invention, the new ruxolitinib preparation route is provided, wherein each reaction of the route has the high yield, the total yield of the route is high, the purity of theobtained product is good, the post-treatment of the reaction is simple, and column chromatography is not required; by adopting the route, the required raw materials or catalysts and other materials are relatively easy to obtain; and compared to the method in the prior art, the method of the present invention is economical and is suitable for industrial production.
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Paragraph 0063; 0064; 0075; 0076
(2018/03/24)
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- Maximizing the Number of Interfacial Sites in Single-Atom Catalysts for the Highly Selective, Solvent-Free Oxidation of Primary Alcohols
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The solvent-free selective oxidation of alcohols to aldehydes with molecular oxygen is highly attractive yet challenging. Interfacial sites between a metal and an oxide support are crucial in determining the activity and selectivity of such heterogeneous catalysts. Herein, we demonstrate that the use of supported single-atom catalysts (SACs) leads to high activity and selectivity in this reaction. The significantly increased number of interfacial sites, resulting from the presence of individually dispersed metal atoms on the support, renders SACs one or two orders of magnitude more active than the corresponding nanoparticle (NP) catalysts. Lattice oxygen atoms activated at interfacial sites were found to be more selective than O2 activated on metal NPs in oxidizing the alcohol substrate. This work demonstrates for the first time that the number of interfacial sites is maximized in SACs, providing a new avenue for improving catalytic performance by developing appropriate SACs for alcohol oxidation and other reactions occurring at metal–support interfacial sites.
- Li, Tianbo,Liu, Fei,Tang, Yan,Li, Lin,Miao, Shu,Su, Yang,Zhang, Junying,Huang, Jiahui,Sun, Hui,Haruta, Masatake,Wang, Aiqin,Qiao, Botao,Li, Jun,Zhang, Tao
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supporting information
p. 7795 - 7799
(2018/06/26)
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- Ordered nanoporous lyotropic liquid crystal polymer resin for heterogeneous catalytic aerobic oxidation of alcohols
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An ordered, nanoporous, TEMPO-based polymer resin formed from lyotropic liquid crystal monomers catalyzes the hetereogeneous oxidation of alcohols with high activity and substrate size selectivity under transition-metal-free, aerobic conditions.
- Dwulet, Gregory E.,Gin, Douglas L.
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supporting information
p. 12053 - 12056
(2018/12/01)
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- Green and selective oxidation of alcohols by immobilized Pd onto triazole functionalized Fe 3O 4 magnetic nanoparticles
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Abstract: Carbonyl compounds were prepared by selective oxidation of alcohols in the presence of recoverable Fe 3O 4@ SiO 2@ Pd magnetic nanocatalyst in aqueous media as a green solvent. Molecular oxygen served as an oxidant. The catalyst was removed from the reaction media by external magnetic field, washed with methanol, and reused for six more times without any considerable reduction in its reactivity. The chemoselectivity and regioselectivity of the catalyst can serve for selective oxidation of primary alcohols in the presence of secondary ones, and for oxidation of unhindered alcohols in the presence of hindered ones. Graphical Abstract: Selective and facile oxidation of alcohols to their corresponding carbonyl compounds in the presence of immobilized, recoverable, and magnetic nano Pd-particles in water by molecular oxygen. [Figure not available: see fulltext.].
- Dadras, Arefeh,Naimi-Jamal, M Reza,Moghaddam, F Matloubi,Ayati, Seyed Ebrahim
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- Production of 1,6-hexanediol from tetrahydropyran-2-methanol by dehydration-hydration and hydrogenation
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In this work we present an alternate method for the conversion of tetrahydropyran-2-methanol (THP2M), a cellulose-derived renewable building block, to 1,6-hexanediol (1,6-HDO). Our method is composed of three consecutive steps that either use relatively inexpensive catalysts or no catalyst at all. First, THP2M is catalytically dehydrated to 2,3,4,5-tetrahydrooxepine (THO) in up to 40% yield. THO is then hydrated to 2-oxepanol (OXL) and 6-hydroxyhexanal (6HDHX) with a combined yield of 85% in the absence of a catalyst. OXL and 6HDHX are then quantitatively hydrogenated to 1,6-HDO over a commercially available Ni/C or Ru/C catalyst. Various silicoaluminates were screened for the first acid-catalyzed reaction, and it was found that K-BEA shows the highest THO yield (40% over fresh catalyst, 20% after 25 h on stream). An overall 1,6-HDO yield of 34% from THP2M was obtained.
- Burt, Samuel P.,Barnett, Kevin J.,McClelland, Daniel J.,Wolf, Patrick,Dumesic, James A.,Huber, George W.,Hermans, Ive
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supporting information
p. 1390 - 1398
(2017/08/15)
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- One-Pot Process for Hydrodeoxygenation of Lignin to Alkanes Using Ru-Based Bimetallic and Bifunctional Catalysts Supported on Zeolite Y
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The synthesis of high-efficiency and low-cost catalysts for hydrodeoxygenation (HDO) of waste lignin to advanced biofuels is crucial for enhancing current biorefinery processes. Inexpensive transition metals, including Fe, Ni, Cu, and Zn, were severally co-loaded with Ru on HY zeolite to form bimetallic and bifunctional catalysts. These catalysts were subsequently tested for HDO conversion of softwood lignin and several lignin model compounds. Results indicated that the inexpensive earth-abundant metals could modulate the hydrogenolysis activity of Ru and decrease the yield of low-molecular-weight gaseous products. Among these catalysts, Ru-Cu/HY showed the best HDO performance, affording the highest selectivity to hydrocarbon products. The improved catalytic performance of Ru-Cu/HY was probably a result of the following three factors: (1) high total and strong acid sites, (2) good dispersion of metal species and limited segregation, and (3) high adsorption capacity for polar fractions, including hydroxyl groups and ether bonds. Moreover, all bifunctional catalysts proved to be superior over the combination catalysts of Ru/Al2O3 and HY zeolite.
- Wang, Hongliang,Ruan, Hao,Feng, Maoqi,Qin, Yuling,Job, Heather,Luo, Langli,Wang, Chongmin,Engelhard, Mark H.,Kuhn, Erik,Chen, Xiaowen,Tucker, Melvin P.,Yang, Bin
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p. 1846 - 1856
(2017/04/27)
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- Rhodium-Complex-Catalyzed Hydroformylation of Olefins with CO2and Hydrosilane
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A rhodium-catalyzed one-pot hydroformylation of olefins with CO2, hydrosilane, and H2has been developed that affords the aldehydes in good chemoselectivities at low catalyst loading. Mechanistic studies indicate that the transformation is likely to proceed through a tandem sequence of poly(methylhydrosiloxane) (PMHS) mediated CO2reduction to CO and a conventional rhodium-catalyzed hydroformylation with CO/H2. The hydrosilylane-mediated reduction of CO2in preference to aldehydes was found to be crucial for the selective formation of aldehydes under the reaction conditions.
- Ren, Xinyi,Zheng, Zhiyao,Zhang, Lei,Wang, Zheng,Xia, Chungu,Ding, Kuiling
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supporting information
p. 310 - 313
(2016/12/30)
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- Transition State-Based Sialyltransferase Inhibitors: Mimicking Oxocarbenium Ion by Simple Amide
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In the new transition-state based sialyltransferase inhibitors, an amide group was placed at the corresponding C-2 position of CMP-sialic acid to mimic the geometry and charge distribution in the transition state, and simple aromatic or aliphatic rings were used instead of the sialic acid moiety. All synthetic compounds exhibited excellent α(2-6)-sialyltransferase inhibition, resulting in up to a 2600-fold higher affinity for the enzyme than CMP-Neu5Ac, suggesting that amide is a key element for simulating transition-state features.
- Guo, Jian,Li, Wenming,Xue, Weiwei,Ye, Xin-Shan
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supporting information
p. 2135 - 2141
(2017/03/17)
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- An investigation on the aqueous-phase hydrodeoxygenation of various methoxy-substituted lignin monomers on Pd/C and HZSM-5 catalysts
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Aqueous phase catalytic upgrading of lignin monomers to hydrocarbons via hydrodeoxygenation (HDO) has been explored using a combination of Pd/C and HZSM-5 catalysts under 2 MPa of H2 (ambient temperature). Model monomers with varying numbers of methoxy groups, including phenol, anisole, guaiacol and 2,6-dimethoxy-phenol, were chosen as lignin model compounds. Mechanistic studies revealed cascade and parallel reaction pathways via hydrogenation and dehydration (hydrolysis) processes, which were catalyzed by Pd/C and HZSM-5, respectively. Hydrogenation was preferred at lower temperature, whereas higher temperature was favorable for the removal of oxygen-containing functional groups. The effect of methoxy groups on the HDO of these monomers was also investigated systematically. Basically, the conversion of multi-substituted monomers was tougher than that of mono-substituted ones, due to steric constraint and the inhibition of the electron-donating hydroxyl group. The selectivities to cyclohexane from phenol and anisole were improved significantly by increasing the temperature to 413 K. However, cyclohexanone was preferably produced over cyclohexane when using model compounds with multi-substituents (guaiacol and 2,6-dimethoxy-phenol), even at temperatures above 513 K. Comparative experiments were also conducted on the HDO of 1,2-cyclohexanediol with or without the presence of phenol, which clearly suggested that the further HDO of guaiacol and 2,6-dimethoxy-phenol was inhibited, probably due to the strong interactions between cyclohexanediol molecules and Br?nsted acid sites.
- Zhang, Cong,Qi, Jingbo,Xing, Jing,Tang, Si-Fu,Song, Liang,Sun, Yuanyuan,Zhang, Chuanhui,Xin, Hongchuan,Li, Xuebing
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p. 104398 - 104406
(2016/11/17)
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- COMPOUNDS AND METHODS OF TREATING OCULAR DISORDERS
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A method of treating an ocular disorder in a subject associated with increased all-trans-retinal in an ocular tissue includes administering to the subject a therapeutically effective amount of a primary amine compound of formula (I); and pharmaceutically acceptable salts thereof.
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Paragraph 00204
(2016/06/14)
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- Difluorocyclobutylacetylenes as positive allosteric modulators of mGluR5 with reduced bioactivation potential
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Schizophrenia is a serious illness that affects millions of patients and has been associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction. It has been demonstrated that activation of metabotropic glutamate receptor 5 (mGluR5) enhances NMDA receptor function, suggesting the potential utility of mGluR5 positive allosteric modulators (PAMs) in the treatment of schizophrenia. Herein we describe the optimization of an mGluR5 PAM by replacement of a phenyl with aliphatic heterocycles and carbocycles as a strategy to reduce bioactivation in a biaryl acetylene chemotype. Replacement with a difluorocyclobutane followed by further optimization culminated in the identification of compound 32, a low fold shift PAM with reduced bioactivation potential. Compound 32 demonstrated favorable brain uptake and robust efficacy in mouse novel object recognition (NOR) at low doses.
- Degnan, Andrew P.,Maxwell, Darrell,Balakrishnan, Anand,Brown, Jeffrey M.,Easton, Amy,Gulianello, Michael,Hanumegowda, Umesh,Hill-Drzewi, Melissa,Miller, Regina,Santone, Kenneth S.,Senapati, Arun,Shields, Eric E.,Sivarao, Digavalli V.,Westphal, Ryan,Whiterock, Valerie J.,Zhuo, Xiaoliang,Bronson, Joanne J.,Macor, John E.
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supporting information
p. 5871 - 5876
(2016/12/06)
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- NOVEL ORGANOLEPTIC COMPOUNDS
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The present invention relates to novel compounds and their use as fragrance materials.
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Paragraph 0057-0060
(2015/03/04)
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- Water-Assisted Selective Hydrodeoxygenation of Lignin-Derived Guaiacol to Monooxygenates
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Water, which frequently inhibits organic reactions, improves the hydrodeoxygenation activity of lignin-derived guaiacol on a bifunctional catalyst of Rh/SiO2-Al2O3 in a biphasic mixture of n-decane and water. The unique properties of subcritical water appear to promote hydrodeoxygenation, which improves the production of monooxygenates by removing more oxygen atoms of guaiacol while suppressing the formation of fully deoxygenated hydrocarbons because of the poor solubility of hydrophobic monooxygenates.
- Yoon, Ji Sun,Choi, Jae-Wook,Suh, Dong Jin,Lee, Kangtaek,Lee, Hyunjoo,Ha, Jeong-Myeong
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p. 2669 - 2674
(2015/09/15)
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- First rhodium-catalyzed hydroformylation of cyclopentadiene
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This paper describes the first rhodium-catalyzed hydroformylation of cyclopentadiene (Cpd) using a homogeneous catalyst system consisting of [Rh(OAc)2]2 and the chelate ligand BISBI. At a reaction temperature of 100°C and a syngas pressure of 30 bar the cyclopentane carbaldehyde is formed in 68% yield while 20% of the respective dialdehyde species are obtained within 3 hours. An important side reaction in Cpd hydroformylation reaction can be the dimerization of Cpd to its dimer dicyclopentadiene (Dcpd). This unwanted side reaction could be overcome by the use of tertiary alkyl amines as additives. Furthermore, the possibility to steer the reaction via the influence of the bite angle of diphosphine ligands was found.
- Behr, Arno,Levikov, Denys,Vogelsang, Dennis
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p. 114 - 117
(2015/06/23)
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- Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration
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All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation.
- Zhang, Jianye,Dong, Zhiqian,Mundla, Sreenivasa Reddy,Hu, X. Eric,Seibel, William,Papoian, Ruben,Palczewski, Krzysztof,Golczak, Marcin
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supporting information
p. 477 - 491
(2015/01/30)
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- Synergistic effects of Ni and acid sites for hydrogenation and C-O bond cleavage of substituted phenols
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The cleavage of C-O bonds in phenol, catechol, and guaiacol has been explored with mono- and dual-functional catalysts containing Ni and/or HZSM-5 in the aqueous phase. The aromatic ring of phenol is hydrogenated in the first step, and the C-O bond of the resulting cyclohexanol is dehydrated in sequence. The initial turnover frequency (TOF) of phenol hydrodeoxygenation increases in parallel with the acid site concentration irrespective of the concentration of the accessible surface Ni atoms. For catechol and guaiacol conversion, Ni catalyzes the hydrogenolysis of the C-O bonds in addition to arene hydrogenation. For catechol, the hydrogenation of the aromatic ring and the hydrogenolysis of the phenolic -OH group occur in parallel with a ratio of 8 : 1. The saturated cyclohexane-1,2-diol can be further dehydrated over HZSM-5 or hydrogenolyzed on Ni to complete hydrodeoxygenation. Guaiacol undergoes primarily hydrogenolysis (75%) to phenol via demethoxylation, and the hydrogenation route accounts for only 25%. This is attributed to the steric effects arising from the adjacent sp3 hybrid O-CH3 group. 2-Methoxycyclohexanol (from guaiacol hydrogenation) reacts further either via hydrogenolysis by Ni to cyclohexanol or via acid catalyzed demethoxylation and rearrangement steps followed by the subsequent hydrogenation of the intermediately formed olefins. On Ni/HZSM-5, the hydrodeoxygenation activities are much higher for the phenolic monomers than for their respective saturated analogues, pointing to the importance of sp2 orbitals. The presence of proximal acid sites increases the activities of Ni in the presence of H2 by a synergistic action. This journal is
- Song, Wenji,Liu, Yuanshuai,Barth, Eszter,Zhao, Chen,Lercher, Johannes A.
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p. 1204 - 1218
(2015/03/04)
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- Hypoiodite-catalyzed regioselective oxidation of alkenes: An expeditious access to aldehydes in aqueous micellar media
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A highly anti-Markovnikov selective oxidation of alkenes based on in situ generated hypoiodite catalysis in aqueous micellar media under mild conditions has been described. This novel catalytic system realizes an efficient synthesis of aldehydes from alkenes in an economically viable and environmentally safe fashion. The preliminary mechanistic studies suggest that the reaction proceeds via tandem iodofunctionalization/1,2-aryl or alkyl migration. The scope and limitations of this tandem process are demonstrated with various mono- and disubstituted (terminal and internal) olefins.
- Swamy, Peraka,Reddy, Marri Mahender,Naresh, Mameda,Kumar, Macharla Arun,Srujana, Kodumuri,Durgaiah, Chevella,Narender, Nama
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p. 1125 - 1130
(2015/04/22)
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- Highly Substituted Cyclopentane-CMP Conjugates as Potent Sialyltransferase Inhibitors
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Sialylconjugates on cell surfaces are involved in many biological events such as cellular recognition, signal transduction, and immune response. It has been reported that aberrant sialylation at the nonreducing end of glycoconjugates and overexpression of sialyltransferases (STs) in cells are correlated with the malignance, invasion, and metastasis of tumors. Therefore, inhibitors of STs would provide valuable leads for the discovery of antitumor drugs. On the basis of the transition state of the enzyme-catalyzed sialylation reaction, we proposed that the cyclopentane skeleton in its two puckered conformations might mimic the planar structure of the donor (CMP-Neu5Ac) in the transition state. A series of cyclopentane-containing compounds were designed and synthesized by coupling different cyclopentane α-hydroxyphosphonates with cytidine phosphoramidite. Their inhibitory activities against recombinant human ST6Gal-I were assayed, and a potent inhibitor 48l with a Ki of 0.028 ± 0.006 μM was identified. The results show that the cyclopentanoid-type compounds could become a new type of sialyltransferase inhibitors as biological probes or drug leads.
- Li, Wenming,Niu, Youhong,Xiong, De-Cai,Cao, Xiaoping,Ye, Xin-Shan
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p. 7972 - 7990
(2015/11/09)
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- Selective hydroformylation of various olefins using diphosphinite ligands
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Novel diphosphinite ligands are synthesized by the reaction of various derivatives of 1,3-diols with chlorodiphenylphosphine. The synthesized ligands exhibited considerable impact on hydroformylation of various olefins with excellent regioselectivity toward branched aldehyde. The effect of solvent, temperature, pressure and catalyst loading on the hydroformylation reaction is also described. The synthesized diphosphinite ligands with rhodium precursor works under milder reaction conditions as compared to traditional phosphine and phosphite-based ligands. Copyright 2013 John Wiley & Sons, Ltd. A novel diphosphinite ligands are synthesized by the reaction of various derivatives of 1,3-diol with chlorodiphenylphosphine. The synthesized ligands exhibited a considerable impact on hydroformylation of various olefins with excellent regioselectivity toward branched aldehyde. The effect of solvent, temperature, pressure and catalyst loading on the hydroformylation reaction is also described. The synthesized diphosphinite ligands with Rhodium precursor works at milder reaction conditions as compared to traditional phosphine and phosphite based ligands. Copyright
- Khan, Shoeb R.,Bhanage, Bhalchandra M.
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p. 313 - 317
(2013/07/04)
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- Selective hydroformylation-acetalization of various olefins using simple and efficient Rh-phosphinite complex catalyst
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A simple and efficient Rh-phosphinite complex catalyst was studied for the selective hydroformylation of various olefins. The influence of various reaction parameters including the effect of temperature, pressure, catalyst loading, time, and solvents was studied. The protocol was also applied for the synthesis of various acetals via tandem hydroformylation-acetalization of olefins in alcohols as solvents. High activity and selectivity for acetal formation was achieved in the absence of co-catalysts with admirable substrate to catalyst mole ratio (TON 2500). The developed protocol works for a wide range of olefins to synthesize corresponding aldehydes and acetals under optimized reaction conditions.
- Khan, Shoeb R.,Bhanage, Bhalchandra M.
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p. 5998 - 6001
(2013/10/22)
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- Site-selective catalysis: Toward a regiodivergent resolution of 1,2-diols
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This paper demonstrates that the secondary hydroxyl can be functionalized in preference to the primary hydroxyl of a 1,2-diol. The site selectivity is achieved by using an enantioselective organic catalyst that is able to bond to the diol reversibly and covalently. The reaction has been parlayed into a divergent kinetic resolution on a racemic mixture, providing access to highly enantioenriched secondary-protected 1,2-diols in a single synthetic step.
- Worthy, Amanda D.,Sun, Xixi,Tan, Kian L.
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supporting information; experimental part
p. 7321 - 7324
(2012/06/16)
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- Intramolecular regioselective addition of radicals and carbanions to ynol ethers. A strategy for the synthesis of exocyclic enol ethers
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The scope and limitations of radical and anionic cyclization reactions involving halo ynol ethers have been investigated. 5-exo and 6-exo radical cyclizations of 6-iodo and 7-iodo ynol ethers proceeded well when the oxygen of the ynol ether was bearing an ethyl group. Exocyclic iodoenol ethers resulting from these cyclizations were highly unstable and decomposed rapidly. Li-I exchange of iodo ynol ethers proceeded smoothly at -78 °C. 6-Alkoxy-5-hexynyllithiums underwent regiospecific 5-exo-dig anionic cyclization to produce five-membered rings bearing an exocyclic enol ether moiety. The cyclized vinyllithium intermediate was successfully trapped with electrophiles to afford functionalized cycloalkoxyalkylidene derivatives in modest to good yields. 7-Alkoxy-6-heptynyllithiums did not cyclize via a 6-exo anionic process.
- Hanna, Rana,Daoust, Benoit
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experimental part
p. 92 - 99
(2011/03/17)
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- Biooxidation of Primary Alcohols to Aldehydes through Hydrogen Transfer Employing Janibacter terrae
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Chemoselective oxidations still represent a challenge for chemists. Lyophilized cells of Janibacter terrae were employed for the chemoselective oxidation of primary alcohols to the corresponding aldehydes by hydrogen transfer with the use of acetaldehyde as the hydrogen acceptor. Secondary alcohol moieties were transformed at a much slower rate. The substrate spectrum encompasses substituted benzyl alcohols, whereby substrates with a substituent in the meta position were well tolerated, whereas only very small substituants were tolerated in the ortho position. Furthermore, nalkanols and allylic alcohols were transformed with good conversions. The biocatalyst was compatible with DMSO as a water miscible organic solvent up to 30 % v/v.
- Orbegozo, Thomas,De Vries, Johannes G.,Kroutil, Wolfgang
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experimental part
p. 3445 - 3448
(2010/09/05)
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- Tandem metal and organocatalysis in sequential hydroformylation and enantioselective mannich reactions
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Metal-catalysed hydroformylation is successfully combined with an organocatalysed stereoselective Mannich reaction in a tandem reaction sequence. This novel type of "tandem catalysis" allows access to complex molecular systems with high levels of enantioselectivity, using simple starting materials and an amino acid as the chiral catalyst.
- Chercheja, Serghei,Rothenbuecher, Thomas,Eilbracht, Peter
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experimental part
p. 339 - 344
(2009/11/30)
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- Oligomeric iodosylbenzene sulfate: A convenient hypervalent iodine reagent for oxidation of organic sulfides and alkenes
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Oligomeric iodosylbenzene sulfate, (PhIO)3·SO 3, which can be formally considered as a partially depolymerized activated iodosylbenzene, is a readily available, stable, and water-soluble hypervalent iodine reagent that is useful for the oxidation of sulfides or alkenes. Furthermore, this reagent can be conveniently generated in situ from (diacetoxyiodo)benzene and sodium bisulfate and used without isolation in oxidations in aqueous solution or under solvent-free conditions. The reaction of iodosylbenzene sulfate in situ with organic sulfides at room temperature affords sulfoxides in high yields without over-oxidation to sulfones, and this reaction is compatible with the presence in the substrate molecule of hydroxy groups, double bonds, benzylic carbon atoms, carboxylate groups, and various substituted phenyl rings. The reaction of an alkene with iodosylbenzene sulfate generated in situ results in oxidative rearrangement to form a ketone or aldehyde. Georg Thieme Verlag Stuttgart.
- Yusubov, Mehman S.,Yusubova, Rosa Y.,Funk, Tatyana V.,Chi, Ki-Whan,Zhdankin, Viktor V.
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experimental part
p. 2505 - 2508
(2009/12/08)
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- Halonium ion-assisted deiodination of styrene-based vicinal iodohydrins followed by rearrangement through phenyl migration
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(Chemical Equation Presented) Acid activation of bromate/bromide couple at 0-10°C was found to trigger the deiodination of styrene-based vicinal iodohydrins. Violet coloration of the organic layer was ascribed to formation of IBr. Deiodination was followed by phenyl migration and deprotonation leading to formation of phenyl acetone and 2-phenylpropanal in good yields from 1-iodo-2-phenylpropan-2-ol and 2-iodo-1-phenylpropan-1-ol, respectively. Phenyl acetaldehyde-which was obtained in 92% GC yield from styrene iodohydrin-was also presumably formed in analogous manner. NBS and HOCl too were effective for transformation of styrene iodohydrin into phenyl acetaldehyde. 2009 American Chemical Society.
- Agrawal, Manoj K.,Ghosh, Pushpito K.
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experimental part
p. 7947 - 7950
(2010/01/16)
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- Synthesis of exo-3-ammo-7-azabicyclo[2.2.1]heptanes as a class of malarial aspartic protease inhibitors: Exploration of two binding pockets
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The increasing prevalence of drug-resisLant strains of malaria-causing Plasmodium parasites necessitates the development of therapeutic agents that inhibit new biochemical targets. We herein describe the design, synthesis, and in vitro evaluation of a class of inhibitors that target the malarial aspartic proteases known as the plasmepsins. The title compounds feature a 7-azanorbornane skeleton that bears an exo-amino function, which was designed to interact with the catalytic dyad of aspartic proteases while providing vectors for the attachment of binding elements that target the flap and S1/S3 binding pockets at. the enzyme active site. Their synthesis takes advantage of a solvent-free and highly diastereoselective conjugate addition of amines to bicyclic vinyl sulfones. Structural optimization based on a little-known conformational preference of aryl sulfones produced the most potent inhibitors of this new class. In vitro assays demonstrate that the title compounds are capable of potent (IC50 ≥ 1.0 nM) inhibition of plasmepsins, while remaining relatively weak inhibitors of the closely related human enzymes cathepsins D and E. The ideal occupation of the flap pocket is crucial for both potency and selectivity over the human proteases. Differently functionalized compounds were synthesized to gain new insights info the molecular recognition properties of this cavity. Wiley-VCH Verlag GmbH & Co. KGaA.
- Zuercher, Martina,Hof, Fraser,Barandun, Luzi,Schuetz, Andri,Schweizer, W. Bernd,Meyer, Solange,Bur, Daniel,Diederich, Francois
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supporting information; experimental part
p. 1707 - 1719
(2009/08/09)
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- Tandem metal- and organocatalysis in sequential hydroformylation and enantioselective aldol reactions
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Metal-catalysed hydroformylation is successfully combined with organocatalysed stereoselective aldol addition into a tandem reaction sequence. This novel type of "tandem catalysis" allows access to complex molecular systems with high levels of enantioselectivity, using simple starting materials and an amino acid as the chiral catalyst.
- Chercheja, Serghei,Eilbracht, Peter
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p. 1897 - 1905
(2008/09/17)
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- Catalytic deprotection of acetals in basic solution with a self-assembled supramolecular "nanozyme"
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(Formula Presented) Changing on the inside: Acetals are a commonly used protecting groups for aldehydes and ketones in organic synthesis because of their ease of installation and resistance to cleavage in neutral or basic solution. A self-assembled supramolecular assembly has been shown to catalyze the hydrolysis of acetals and ketals in basic solution (see scheme).
- Pluth, Michael D.,Bergman, Robert G.,Raymond, Kenneth N.
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p. 8587 - 8589
(2008/09/18)
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- Synthesis of novel cyclopropylic sulfones and sulfonamides acting as glucokinase activators
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A synthetic route towards cyclopropylic compounds, which act as glucokinase activators is described herein. The present synthesis gives easy and rapid access to a wide variety of either sulfones or sulfonamides starting from readily available late-stage intermediates.
- Heuser, Stefan,Barrett, David G.,Berg, Martina,Bonnier, Benjamin,Kahl, Astrid,De La Puente, Maria Luz,Oram, Niall,Riedl, Rainer,Roettig, Ulrike,Gil, Gema Sanz,Seger, Erich,Steggles, David J.,Wanner, Jutta,Weichert, Andreas G.
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p. 2675 - 2678
(2007/10/03)
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- Three-phase microemulsion/sol-gel system for aqueous catalytic hydroformylation of hydrophobie alkenes
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We extended the three-phase transport methodology to the catalytic hydroformylation of alkenes. The method enables to carry out an all-hydrophobic reaction - substrate, product and catalyst - in water. The alkene is microemulsified in the aqueous medium and the solubilized substrate is assumed to be carried to an organometallic rhodium catalyst entrapped within a partially hydrophobicized silica sol-gel matrix. The substrate is then spilled into the porous heterogenized catalyst in which the hydroformylation takes place. The products formed are desorbed from the ceramic material and microemulsified by the same surfactant. Upon breaking of the microemulsion the products are separated. The heterogenized catalyst can be easily separated from the reaction mixture by filtration and be recycled. The hydroformylation process was carried out on various alkenes with reaction yields from ca. 62 to 99%. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Abu-Reziq, Raed,Avnir, David,Blum, Jochanan
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p. 3640 - 3642
(2007/10/03)
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- New oxidative transformations of alkenes and alkynes under the action of diacetoxyiodobenzene
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Treatment of alkenes and alkynes with diacetoxyiodobenzene activated by mineral and organic acids predominantly results in oxidative rearrangement. 1,4-Diphenylbutadiene in MeOH gives 3,4-dimethoxy-1,4-diphenylbut-1-ene.
- Yusubov,Zholobova,Filimonova,Chi, Ki-Whan
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p. 1735 - 1742
(2007/10/03)
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- Trifluoromethylthiocopper catalyzed oxirane ring opening
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Trifluoromethylthiocopper has been found to catalyze the opening of the epoxide ring and to furnish not-so-easily accessible novel trifluoromethylthiolated α-hydroxy compounds. This communication presents the mechanism of the formation of the various comp
- Munavalli,Rohrbaugh,Durst
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p. 1657 - 1671
(2007/10/03)
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- Erbium(III) triflate: A valuable catalyst for the rearrangement of epoxides to aldehydes and ketones
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Rearrangement of epoxides is performed with erbium triflate as catalyst. In contrast to most proposed catalysts for this re-action, erbium triflate works well with both aromatic and aliphatic epoxides.
- Procopio, Antonio,Dalpozzo, Renato,De Nino, Antonio,Nardi, Monica,Sindona, Giovanni,Tagarelli, Antonio
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p. 2633 - 2635
(2007/10/03)
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- TEMPO-mediated environmentally benign oxidation of primary alcohols to carboxylic acids with poly[4-(diacetoxyiodo)styrene]
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An operationally simple and environmentally benign oxidation of primary alcohols to the corresponding carboxylic acids with a TEMPO-mediated poly[4-(diacetoxyiodo)styrene] system in acetone and water was carried out.
- Tashino, Yousuke,Togo, Hideo
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p. 2010 - 2012
(2007/10/03)
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- SUBSTITUTED ARYLCYCLOPROPYLACETAMIDES AS GLUCOKINASE ACTIVATORS
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According to the present invention there is provided a compounds of formula (I): and pharmaceutically acceptable salts thereof.
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- DIARYL ETHERS AS OPIOID RECEPTOR ANTAGONIST
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A compound of the formula (I) wherein the variables X1 to X10, R1 to R7 including R3', E, v, y, z, A and B are as described, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.
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Page/Page column 90
(2008/06/13)
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- Photochemical synthesis of highly functionalized cyclopropyl ketones
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A series of di- and trisubstituted cyclopropyl ketones 11 were prepared by irradiation of ketones 3 and 5, which bear a leaving group adjacent to the carbonyl C-atom. The required ketones 3 could be easily synthesized either by functionalization of ketones 1 with a hypervalent iodine reagent, 2, or by O-sulfonylation of α-hydroxy ketones 7. The nitrates 5 were obtained by treatment of the corresponding α-bromo ketones with AgNO3. The irradiation of 3 and 5 must be performed in the presence of an acid scavenger (1-methyl-1H-imidazole) to obtain the cyclopropanes 11 in good yields. The synthetic efficiency of the method was, among other things, demonstrated by the preparation of a highly strained bicyclo[2.1.0]pentane 11i in good yield. The mechanism of the photochemical cyclization was investigated by means of photokinetic measurements, as well as by quantum-chemical calculations. It was shown that the presence of the leaving group substantially influences all steps of the photochemical reaction cascade. The X-ray crystal structures of 11j and exo-11k were also determined.
- Wessig, Pablo,Muehling, Olaf
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p. 865 - 893
(2007/10/03)
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- Isoxazolo pyrimidinones and the use thereof
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The invention relates to novel isoxazolo pyrimidinones of general formula (I), a method for producing the same and the pharmaceutical use thereof.
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- Viral polymerase inhibitors
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An isomer, enantiomer, diastereoisomer, or tautomer of a compound, represented by formula I: wherein: A is O, S, NR1, or CR1, wherein R1 is defined herein; ---- represents either a single or a double bond; R2 is selected from: H, halogen, R21, OR21, SR21, COOR21, SO2N(R22)2, N(R22)2, CON(R22)2, NR22C(O)R22 or NR22C(O)NR22 wherein R21 and each R22 is defined herein; B is NR3 or CR3, with the proviso that one of A or B is either CR1 or CR3, wherein R3 is defined herein; K is N or CR4, wherein R4 is defined herein; L is N or CR5, wherein R5 has the same definition as R4 defined above; M is N or CR7, wherein R7 has the same definition as R4 defined above; Y1 is O or S; Z is N(R6a)R6 or OR6, wherein R6a is H or alkyl or NR61R62 wherein R61 and R62 are defined herein; a salt or a derivative thereof, as an inhibitor of HCV NS5B polymerase.
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- A facile method for the conversion of oximes and tosylhydrazones to carbonyl compounds with Cr-MCM-41 zeolite under microwave irradiation
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Cr-MCM-41 zeolite supported on silica gel can be used as an effective and mild oxidizing agent for the direct conversion of oximes and tosylhydrazones to carbonyl compounds under microwave irradiation in good yield. The procedure is applicable to the variety of oximes and tosylhydrazones and the zeolite can be recycled.
- Nagarapu, Lingaiah,Ravirala, Narender,Akkewar, Dattatray
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p. 2195 - 2202
(2007/10/03)
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- A new photochemical route to cyclopropanes
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Especially highly substituted cyclopropanes can be produced with a new photochemical approach. Starting with aromatic ketones that bear a leaving group adjacent to the carbonyl carbon atom, photolysis leads to the formation of 1,3-diradicals, which efficiently cyclize to cyclopropanes (see scheme; Ms=MeSO2).
- Wessig, Pablo,Muehling, Olaf
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p. 1064 - 1065
(2007/10/03)
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