- Realization of an Asymmetric Non-Aqueous Redox Flow Battery through Molecular Design to Minimize Active Species Crossover and Decomposition
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This communication presents a mechanism-based approach to identify organic electrolytes for non-aqueous redox flow batteries (RFBs). Symmetrical flow cell cycling of a pyridinium anolyte and a cyclopropenium catholyte resulted in extensive capacity fade due to competing decomposition of the pyridinium species. Characterization of this decomposition pathway enabled the rational design of next-generation anolyte/catholyte pairs with dramatically enhanced cycling performance. Three factors were identified as critical for slowing capacity fade: (1) separating the anolyte–catholyte in an asymmetric flow cell using an anion exchange membrane (AEM); (2) moving from monomeric to oligomeric electrolytes to limit crossover through the AEM; and (3) removing the basic carbonyl moiety from the anolyte to slow the protonation-induced decomposition pathway. Ultimately, these modifications led to a novel anolyte–catholyte pair that can be cycled in an AEM-separated asymmetric RFB for 96 h with >95 % capacity retention at an open circuit voltage of 1.57 V.
- Hendriks, Koen H.,Minteer, Shelley D.,Sanford, Melanie S.,Shrestha, Anuska,Sigman, Mathew S.
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Read Online
- Electronic Effect-Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols
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Herein, we developed an electronic effect-guided rational design strategy to enhance the enantioselectivity of Candida antarctica lipase B (CALB) mutants towards bulky pyridyl(phenyl)methanols. Compared to W104A mutant previously reported with reversed S-stereoselectivity toward sec-alcohols, three mutants (W104C, W104S and W104T) displayed significant improvement of S-enantioselectivity in the kinetic resolution (KR) of various phenyl pyridyl methyl acetates due to the increased electronic effects between pyridyl and polar residues. The electronic effects were also observed when mutating other residues surrounding the stereospecificity pocket of CALB, such as T42A, S47A, A281S or A281C, and can be used to manipulate the stereoselectivity. A series of bulky pyridyl(phenyl) methanols, including S-(4-chlorophenyl)(pyridin-2-yl) methanol (S-CPMA), the intermediate of bepotastine, were obtained in good yields and ee values. (Figure presented.).
- Li, Dan-Yang,Lou, Yu-Jiao,Xu, Jian,Chen, Xiao-Yang,Lin, Xian-Fu,Wu, Qi
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supporting information
p. 1867 - 1872
(2021/02/12)
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- Tunable System for Electrochemical Reduction of Ketones and Phthalimides
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Herein, we report an efficient, tunable system for electrochemical reduction of ketones and phthalimides at room temperature without the need for stoichiometric external reductants. By utilizing NaN3 as the electrolyte and graphite felt as both the cathode and the anode, we were able to selectively reduce the carbonyl groups of the substrates to alcohols, pinacols, or methylene groups by judiciously choosing the solvent and an acidic additive. The reaction conditions were compatible with a diverse array of functional groups, and phthalimides could undergo one-pot reductive cyclization to afford products with indolizidine scaffolds. Mechanistic studies showed that the reactions involved electron, proton, and hydrogen atom transfers. Importantly, an N3/HN3 cycle operated as a hydrogen atom shuttle, which was critical for reduction of the carbonyl groups to methylene groups.
- Chen, Gong,Qiao, Tianjiao,Wang, Yaxin,Zhang, Jian,Zhao, Jianyou
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supporting information
p. 3297 - 3302
(2021/10/14)
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- Electrochemical Arylation of Aldehydes, Ketones, and Alcohols: from Cathodic Reduction to Convergent Paired Electrolysis
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Arylation of carbonyls, one of the most common approaches toward alcohols, has received tremendous attention, as alcohols are important feedstocks and building blocks in organic synthesis. Despite great progress, there is still a great gap to develop an ideal arylation method featuring mild conditions, good functional group tolerance, and readily available starting materials. We now show that electrochemical arylation can fill the gap. By taking advantage of synthetic electrochemistry, commercially available aldehydes (ketones) and benzylic alcohols can be readily arylated to provide a general and scalable access to structurally diverse alcohols (97 examples, >10 gram-scale). More importantly, convergent paired electrolysis, the ideal but challenging electrochemical technology, was employed to transform low-value alcohols into more useful alcohols. Detailed mechanism study suggests that two plausible pathways are involved in the redox neutral α-arylation of benzylic alcohols.
- Zhang, Sheng,Li, Lijun,Li, Jingjing,Shi, Jianxue,Xu, Kun,Gao, Wenchao,Zong, Luyi,Li, Guigen,Findlater, Michael
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supporting information
p. 7275 - 7282
(2021/03/01)
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- Reductive arylation of aliphatic and aromatic aldehydes with cyanoarenes by electrolysis for the synthesis of alcohols
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An electroreductive arylation reaction of aliphatic and aromatic aldehydes as well as ketones with electro-deficient (hetero)arenes is described. A variety of cyano(hetero)arenes and carbonyl compounds, especially aliphatic aldehydes, have been examined, providing secondary and tertiary alcohols in moderate to good yields. Mechanistic studies, including cyclic voltammetry (CV), electron paramagnetic resonance (EPR), and divided-cell experiments, support the generation of aliphatic ketyl radicals and persistent heteroaryl radical anions via cathodic reduction followed by radical-radical cross-coupling.
- Zhang, Xiao,Yang, Chao,Gao, Han,Wang, Lei,Guo, Lin,Xia, Wujiong
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supporting information
p. 3472 - 3476
(2021/05/10)
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- Transition-Metal Free Chemoselective Hydroxylation and Hydroxylation-Deuteration of Heterobenzylic Methylenes
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We developed an approach for direct selective hydroxylation of heterobenzylic methylenes to secondary alcohols avoiding overoxidation to ketones by using a KOBu-t/DMSO/air system. Most reactions could reach completion in several minutes to give hydroxylated products in 41-76% yields. Using DMSO-d6, this protocol resulted in difunctionalization of heterobenzylic methylenes to afford α-deuterated secondary alcohols (>93% incorporation). By employing this method, active pharmaceutical ingredients carbinoxamine and doxylamine were synthesized in two steps in moderate yields.
- Fu, Yiwei,Li, Hao,Liu, Yonghai,Mang, Zhiguo,Shi, Lei,Sun, Chengyu,Yu, Yang
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supporting information
p. 8127 - 8131
(2020/11/03)
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- Benzylic C-H heteroarylation of: N-(benzyloxy)phthalimides with cyanopyridines enabled by photoredox 1,2-hydrogen atom transfer
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A visible light initiated α-C(sp3)-H arylation of N-(benzyloxy)phthalimides with cyanopyridines for the construction of highly valuable pyridinyl-containing diarylmethanols, including bioactive motif-based analogues, is reported. This method enables arylation of the C(sp3)-H bonds adjacent to an oxygen atom through alkoxy radical formation by O-N bond cleavage, 1,2-hydrogen atom transfer (HAT), arylation and C-CN bond cleavage cascades, and offers a means to exploit 1,2-HAT modes to incorporate functional groups for constructing functionalized alcohols.
- Zhong, Long-Jin,Wang, Hong-Yu,Ouyang, Xuan-Hui,Li, Jin-Heng,An, De-Lie
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supporting information
p. 8671 - 8674
(2020/08/21)
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- Electrochemical Hydrogenation with Gaseous Ammonia
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As a carbon-free and sustainable fuel, ammonia serves as high-energy-density hydrogen-storage material. It is important to develop new reactions able to utilize ammonia as a hydrogen source directly. Herein, we report an electrochemical hydrogenation of alkenes, alkynes, and ketones using ammonia as the hydrogen source and carbon electrodes. A variety of heterocycles and functional groups, including for example sulfide, benzyl, benzyl carbamate, and allyl carbamate were well tolerated. Fast stepwise electron transfer and proton transfer processes were proposed to account for the transformation.
- Li, Jin,He, Lingfeng,Liu, Xu,Cheng, Xu,Li, Guigen
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supporting information
p. 1759 - 1763
(2019/01/16)
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- Highly Enantioselective Hydrogenation of Non- ortho-Substituted 2-Pyridyl Aryl Ketones via Iridium- f-Diaphos Catalysis
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This work disclosed a highly enantioselective hydrogenation of non-ortho-substituted 2-pyridyl aryl ketones via Ir/f-diaphos catalysis. This catalytic system allows for full control over the configuration of the stereocenter, affording two enantiomers of the desired products with extremely high enantioselectivity (up to >99% ee in most cases) and excellent reactivity (TON of up to 19600, TOF of 1633 h-1) under mild conditions. Density functional theory calculations and control experiments revealed that the relay hydrogen bonding among the solvent isopropanol, substrate, and ligand is crucial for high ee's.
- Nian, Sanfei,Ling, Fei,Chen, Jiachen,Wang, Ze,Shen, Haiwei,Yi, Xiao,Yang, Yun-Fang,She, Yuanbin,Zhong, Weihui
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supporting information
p. 5392 - 5396
(2019/08/01)
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- Photo-induced reductive cross-coupling of aldehydes, ketones and imines with electron-deficient arenes to construct aryl substituted alcohols and amines
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Umpolung reactions of C=X bonds (X = O, N) are valuable ways of constructing new C–C bonds, which are sometimes difficult to be constructed using traditional synthetic pathways. Classical polarity inversion of C=X bonds (X = O, N) usually requires air or moisture-sensitive and strong reducing agents, which limit the feasibility of substrate scope. Herein we describe a photo-induced reductive cross-coupling reaction of aldehydes, ketones and imines with electron-deficient arenes (aromatic nitriles) using fac-Ir(ppy)3 as a photocatalyst and diisopropylethylamine (DIPEA) as a terminal reductant under visible light irradiation. Mild conditions and high yields mean that this new polarity inversion strategy can be used with aryl-substituted alcohols and amines. Spectroscopic studies and control experiments have demonstrated the oxidative quenching of Ir(ppy)3* by electron-deficient arenes involved in the key step for the C–C bond formation.
- Liu, Zan,Nan, Xiaolei,Lei, Tao,Zhou, Chao,Wang, Yang,Liu, Wenqiang,Chen, Bin,Tung, Chenho,Wu, Lizhu
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p. 487 - 494
(2018/03/22)
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- Direct allylation of benzyl alcohols, diarylmethanols, and triarylmethanols mediated by XtalFluor-E
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We report the direct allylation of benzyl alcohols, diarylmethanols and triarylmethanols mediated by XtalFluor-E using allyltrimethylsilane. The resulting allylated products are obtained in moderate to high yield.
- Lebleu, Thomas,Paquin, Jean-Fran?ois
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supporting information
p. 442 - 444
(2017/01/10)
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- Metal-Free Synthesis of C-4 Substituted Pyridine Derivatives Using Pyridine-boryl Radicals via a Radical Addition/Coupling Mechanism: A Combined Computational and Experimental Study
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Density functional theory investigations revealed that the pyridine-boryl radical generated in situ using 4-cyanopyridine and bis(pinacolato)diboron could be used as a bifunctional “reagent”, which serves as not only a pyridine precursor but also a boryl radical. With the unique reactivity of such radicals, 4-substituted pyridine derivatives could be synthesized using α,β-unsaturated ketones and 4-cyanopyridine via a novel radical addition/C-C coupling mechanism. Several controlled experiments were conducted to provide supportive evidence for the proposed mechanism. In addition to enones, the scope could be extended to a wide range of boryl radical acceptors, including various aldehydes and ketones, aryl imines and alkynones. Lastly, this transformation was applied in the late-stage modification of a complicated pharmaceutical molecule.
- Wang, Guoqiang,Cao, Jia,Gao, Liuzhou,Chen, Wenxin,Huang, Wenhao,Cheng, Xu,Li, Shuhua
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supporting information
p. 3904 - 3910
(2017/03/20)
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- Copper-Catalyzed Aerobic Oxygenation of Benzylpyridine N-Oxides and Subsequent Post-Functionalization
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A copper-catalyzed aerobic oxidation of benzylpyridine N-oxides is reported. The N-oxide moiety acts as a built-in activator for the benzylic methylene oxidation, without requirement of additives. Reaction conditions were identified which suppress undesired benzoylpyridine formation via N-deoxygenation involving intermolecular oxygen transfer. The versatility of the N-oxide group of the benzoylpyridine N-oxide reaction products for post-functionalization of the pyridine ring is demonstrated through efficient C–C, C–N, C–O and C–Cl bond forming procedures, with both nucleophiles and electrophiles. Finally, the applicability of the new synthetic methodology is demonstrated in an alternative route towards the antihistaminic drug Acrivastine via three consecutive N-oxide activated C–H functionalization processes, starting from picoline N-oxide. (Figure presented.).
- Sterckx, Hans,Sambiagio, Carlo,Médran-Navarrete, Vincent,Maes, Bert U. W.
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p. 3226 - 3236
(2017/09/13)
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- Transition-Metal-Free Decarboxylative Photoredox Coupling of Carboxylic Acids and Alcohols with Aromatic Nitriles
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A transition-metal-free protocol for the redox-neutral light-induced decarboxylative coupling of carboxylic acids with (hetero)aromatic nitriles at ambient temperature is presented. A broad scope of acids and nitriles is accepted, and alcohols can be coupled in a similar fashion through their oxalate half esters. Various inexpensive sources of UV light and even sunlight can be used to achieve this C-C bond formation proceeding through a free radical mechanism.
- Lipp, Benjamin,Nauth, Alexander M.,Opatz, Till
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p. 6875 - 6882
(2016/08/16)
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- Palladium-Catalyzed Benzylic Arylation of Pyridylmethyl Silyl Ethers: One-Pot Synthesis of Aryl(pyridyl)methanols
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An efficient palladium-catalyzed direct arylation of pyridylmethyl silyl ethers with aryl bromides is described. A Pd(OAc)2/NIXANTPHOS-based catalyst provides aryl(pyridyl)methyl alcohol derivatives in good to excellent yields (33 examples, 57-100% yield). This protocol is compatible with different silyl ether protecting groups, affording either the protected or the free alcohols in an effective one-pot process. The scalability of the reaction is demonstrated.
- Rivero, Alexandra R.,Kim, Byeong-Seon,Walsh, Patrick J.
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supporting information
p. 1590 - 1593
(2016/05/02)
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- PBr3-mediated unexpected reductive deoxygenation of α-aryl-pyridinemethanols: Synthesis of arylmethylpyridines
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PBr3-mediated reductive deoxygenation of α-aryl-pyridinemethanols to provide arylmethylpyridines is described, the alcohol substrate scope is explored, free radical trap TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) is introduced, and the hydrogen source of the methylene product is defined. The unexpected reaction enabled us to prepare previously inaccessible, novel EP1 antagonists.
- Nishigaya, Yosuke,Umei, Kentaro,Watanabe, Daisuke,Kohno, Yasushi,Seto, Shigeki
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supporting information
p. 1566 - 1572
(2016/03/01)
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- Aerobic oxidation of secondary pyridine-derivative alcohols in the presence of carbon-supported noble metal catalysts
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Pt/C and PtBi/C catalysts prepared on a synthetic mesoporous carbon were evaluated in the oxidation of secondary aromatic alcohols (1-phenylethanol, α-methyl or phenyl pyridinemethanol) with air in different dioxane/water mixtures at 100 °C under 10 bar air. The observed activity for all substrates over both types of catalysts was strongly improved with the addition of water to the dioxane solvent as a result of different interactions of the alcohols with the metallic surface in the apolar dioxane solvent or polar aqueous medium. A promoting effect of bismuth was observed for all substrates. However, the reaction rate was also dramatically influenced by the nature of the aromatic moiety, the nature of the α-group, and the position of the substituent on the pyridine moiety. As a general rule the reactivity was meta para ortho and the pyridine derivatives with a phenyl group were more reactive. α-Phenyl-2-pyridinemethanol was totally converted to 2-benzoylpyridine with a selectivity of 96% in dioxane/water 50/50 vol% in the presence of a 2.7% Pt-0.9% Bi/C. Nevertheless, platinum leaching was detected, which could be limited with the promotion by bismuth.
- Frassoldati, Antonio,Pinel, Catherine,Besson, Michèle
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p. 133 - 138
(2013/08/24)
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- Rabbit 3-hydroxyhexobarbital dehydrogenase is a NADPH-preferring reductase with broad substrate specificity for ketosteroids, prostaglandin D2, and other endogenous and xenobiotic carbonyl compounds
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3-Hydroxyhexobarbital dehydrogenase (3HBD) catalyzes NAD(P) +-linked oxidation of 3-hydroxyhexobarbital into 3-oxohexobarbital. The enzyme has been thought to act as a dehydrogenase for xenobiotic alcohols and some hydroxysteroids, but its physiological function remains unknown. We have purified rabbit 3HBD, isolated its cDNA, and examined its specificity for coenzymes and substrates, reaction directionality and tissue distribution. 3HBD is a member (AKR1C29) of the aldo-keto reductase (AKR) superfamily, and exhibited high preference for NADP(H) over NAD(H) at a physiological pH of 7.4. In the NADPH-linked reduction, 3HBD showed broad substrate specificity for a variety of quinones, ketones and aldehydes, including 3-, 17- and 20-ketosteroids and prostaglandin D2, which were converted to 3α-, 17β- and 20α-hydroxysteroids and 9α,11β- prostaglandin F2, respectively. Especially, α-diketones (such as isatin and diacetyl) and lipid peroxidation-derived aldehydes (such as 4-oxo- and 4-hydroxy-2-nonenals) were excellent substrates showing low Km values (0.1-5.9 μM). In 3HBD-overexpressed cells, 3-oxohexobarbital and 5β-androstan-3α-ol-17-one were metabolized into 3-hydroxyhexobarbital and 5β-androstane-3α,17β-diol, respectively, but the reverse reactions did not proceed. The overexpression of the enzyme in the cells decreased the cytotoxicity of 4-oxo-2-nonenal. The mRNA for 3HBD was ubiquitously expressed in rabbit tissues. The results suggest that 3HBD is an NADPH-preferring reductase, and plays roles in the metabolisms of steroids, prostaglandin D2, carbohydrates and xenobiotics, as well as a defense system, protecting against reactive carbonyl compounds.
- Endo, Satoshi,Matsunaga, Toshiyuki,Matsumoto, Atsuko,Arai, Yuki,Ohno, Satoshi,El-Kabbani, Ossama,Tajima, Kazuo,Bunai, Yasuo,Yamano, Shigeru,Hara, Akira,Kitade, Yukio
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p. 1366 - 1375
(2013/11/19)
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- Kinetic resolution of diarylmethanols using a mutated variant of lipase CALB
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An enzymatic kinetic resolution of diarylmethanols via acylation has been developed. This was achieved by the use of a mutated variant of CALB that accepts larger substrates compared to the wild type. By the use of diarylmethanols with two differently sized aryl groups, enantioselective transformations were achieved. A larger size-difference led to a higher enantioselectivity. In addition, substrates with electronically different aryl groups, such as phenyl and pyridyl, also gave an enantioselective reaction. The highest E value was observed with a substrate where steric and electronic effects were combined.
- Engstr?m, Karin,Vallin, Michaela,Hult, Karl,B?ckvall, Jan-E.
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body text
p. 7613 - 7618
(2012/09/07)
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- METHOD FOR SYNTHESIS OF SECONDARY ALCOHOLS
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A method for synthesis of secondary alcohols is provided for pharmaceutical secondary alcohol by addition of organoboronic acids with aldehydes in presence of the cobalt ion and bidentate ligands as the catalyst. In addition, an enantioselective synthesis method for secondary alcohols is also herein provided in the present invention. The present invention has advantages in using less expensive cobalt ion and commercially available chiral ligands as the catalyst, wide scope of organoboronic acids and aldehydes compatible with this catalytic reaction and achieving excellent yields and/or enantiomeric excess.
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Page/Page column 2
(2012/06/16)
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- Cobalt-catalyzed addition reaction of organoboronic acids with aldehydes: Highly enantioselective synthesis of diarylmethanols
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Predicted outcomes: The addition reaction of organoboronic acids with aldehydes in the presence of K2CO3 catalyzed by CoI 2/ACHTUNGRE(R,R)-BDPP gives chiral secondary alcohols in excellent yields with 90-99 % enantiomeric excess (see scheme; (R,R)-BDPP = (2R,4R)-(+)-2,4-bis(diphenyl-phosphino)pentane). This method provides an alternative to prepare an R and S enantiomeric pair by using the same chiral ligand and allows the stereochemical outcome of the reaction to be predicted.
- Karthikeyan, Jaganathan,Jeganmohan, Masilamani,Cheng, Chien-Hong
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supporting information; experimental part
p. 8989 - 8992
(2010/10/02)
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- PIPERAZINYL DERIVATIVES USEFUL AS MODULATORS OF THE NEUROPEPTIDE Y2 RECEPTOR
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The present invention is directed to piperidinyl and piperazinyl derivatives of formula (II) useful as inhibitors of the NPY Y2 receptor, pharmaceutical compositions comprising said compounds, processes for the preparation of said compounds and the use of said compounds for the treatment and / or prevention of disorders, diseases and conditions mediated by the NPY Y2 receptor.
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Page/Page column 74-75
(2009/07/18)
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- Ruthenium(II) complex catalysts bearing a pyridyl-supported pyrazolyl-imine ligand for transfer hydrogenation of ketones
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A new class of hemilabile unsymmetrical 2-(1-arylimino)-6-(pyzazol-1-yl)pyridine ligands and their ruthenium(II) and nickel(II) NNN complexes were synthesized. The Ru(II) complex catalysts have been fully characterized and exhibited good to excellent catalytic activity in the transfer hydrogenation (TH) of ketones in refluxing 2-propanol. These results have demonstrated rare examples of active ruthenium(II) NNN complex catalysts that do not feature a N-H functionality for TH of ketones.
- Zhao, Miao,Yu, Zhengkun,Yan, Shenggang,Li, Yang
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experimental part
p. 3068 - 3075
(2009/12/08)
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- Kinetics and mechanism of the reaction of Cr(II) aqua ions with benzoylpyridine N-oxide
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Aqueous chromium(II) ions, Craq2+, react with benzoylpyridine oxide (BPO) much more rapidly than with other pyridine N-oxides previously explored. The kinetics were studied under pseudo-first order conditions with either reagent in excess. Under both sets of conditions, the major kinetic term exhibits first order dependence on limiting reagent, and second order dependence on excess reagent, i.e. kCr = k2Cr[BPO][Craq2+]2 (excess Craq2+), and kBPO = k2BPO[Craq2+][BPO]2 (excess BPO), where k2Cr = (6.90 +/- 0.27) x 104 M-2s-1 and k2BPO = (3.32 +/- 0.28) x 105 M-2s-1 in 0.10 M HClO4. The rate constant k2Cr contains terms corresponding to [H+]-independent and [H+]-catalyzed paths. In the proposed mechanism, the initially formed Craq(BPO)2+ engages in parallel oxidation of Craq2+ and reduction of BPO. The latter reaction provides the basis for a convenient new preparative route for the BPO complex of Cr(III).
- Cheng, Mingming,Bakac, Andreja
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p. 2077 - 2082
(2008/02/12)
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- Design, synthesis, and structure-activity relationships of pyrazolo[3,4-d]pyrimidines: A novel class of potent enterovirus inhibitors
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A series of pyrazolo[3,4-d]pyrimidines were synthesized and their antiviral activity was evaluated in a plaque reduction assay. It is very interesting that this class of compounds provide remarkable evidence that they are very specific for human enteroviruses, in particular, coxsackieviruses. Some derivatives proved to be highly effective in inhibiting enterovirus replication at nanomolar concentrations. SAR studies revealed that the phenyl group at the N-1 position and the hydrophobic diarylmethyl group at the piperazine largely influenced the in vitro antienteroviral activity of this new class of potent antiviral agents. It was found that the pyrazolo[3,4-d]pyrimidines with a thiophene substituent, such as compounds 20-24, in general exhibited high activity against coxsackievirus B3 (IC50=0.063-0.089μM) and moderate activity against enterovirus 71 (IC50=0.32-0.65μM) with no apparent cytotoxic effect toward RD (rhabdomyosarcoma) cell lines (CC5025μ M).
- Chern, Jyh-Haur,Shia, Kak-Shan,Hsu, Tsu-An,Tai, Chia-Liang,Lee, Chung-Chi,Lee, Yen-Chun,Chang, Chih-Shiang,Tseng, Sung-Nien,Shih, Shin-Ru
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p. 2519 - 2525
(2007/10/03)
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- The redox chemistry of 4-benzoyi-N′-methyipyridinium cations in acetonitrile with and without proton donors: The role of hydrogen bonding
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In anhydrous CH3CN, 4-benzoyl-W-methyIpyridinium cations undergo two reversible, well-separated (ΔE1/2 ~ 0.6 V) one-electron reductions in analogy to quinones and viologens. If the solvent contains weak protic acids, such as water or alcohols, the first cyclic voltammetric wave remains unaffected while the second wave is shifted closer to the first. Both voltammetric and spectroelectrochemical evidence suggest that the positive shift of the second wave is due to hydrogen bonding between the two-electron reduced form of the ketone and the proton donors. While the one-electron reduction product is stable both in the presence and in the absence of the weak-acid proton donors, the two-electron reduction wave is reversible only in the time scale of cyclic voltammetry. Interestingly, at longer times, the hydrogen bonded adduct reacts further giving nonquaternized 4-benzoylpyridine and 4-(a-hydroxybenzyl)pyridine as the two main terminal products. In the presence of stronger acids, such as acetic acid, the second wave merges quickly with the first, producing an irreversible two-electron reduction wave. The only terminal product in this case is the quatemized 4-(α-hydroxybenzyl)-N-methyIpyridinium cation. Experimental evidence points toward a common mechanism for the formation of the nonquaternized products in the presence of weaker acids and the quaternized product in the presence of CH3CO2H.
- Leventis, Nicholas,Elder, Ian A.,Gao, Xuerong,Bohannan, Eric W.,Sotiriou-Leventis, Chariklia,Rawashdeh, Abdel Monem M.,Overschmidt, Travis J.,Gaston, Kimberly R.
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p. 3663 - 3674
(2007/10/03)
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- New syntheses of substituted pyridines via bromine-magnesium exchange
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Bromine-magnesium exchange using iPrMgCl in THF at room temperature on 2-, 3- and 4-bromopyridines allowed the synthesis of various functionalized pyridines. The methodology was successfully used for the synthesis of 4- azaxanthone. Moreover, single exchange reactions observed on 2,6-, 3,5-, 2,3- and 2,5-dibromopyridines, with complete regioselectivity in the case of 2,3- and 2,5-dibromopyridines, afforded substituted bromopyridines, which were then involved in a second exchange step to provide difunctionalized pyridines. (C) 2000 Elsevier Science Ltd.
- Trécourt, Fran?ois,Breton, Gilles,Bonnet, Véronique,Mongin, Florence,Marsais, Francis,Quéguiner, Guy
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p. 1349 - 1360
(2007/10/03)
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- SUBSTITUTED 1-INDOLYLPROPYL-4-BENZYL-TETRAHYDROPYRIDINE DERIVATIVES
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A class of 1-[3-(1H-indol-3-yl)propyl]-4-benzyl-1,2,5,6-tetrahydropyridine derivatives, substituted at the 5-position of the indole nucleus by a 1,2,4-triazol-4-yl moiety, and on the methylene linkage of the benzyl moiety by an alkyl, alkoxy, or alkoxy-alkoxy substituent, are selective agonists of 5-HT 1-like receptors, being potent agonists of the human 5-HT 1Dα receptor subtype while possessing at least a 10-fold selective affinity for the 5HT 1D. alpha. receptor subtype relative to the 5-HT 1Dβ subtype. They are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT 1Dα receptors is indicated, and are expected to have fewer undesirable cardiovascular and other side effects.
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- Carbonyl reductase activity exhibited by pig testicular 20β- hydroxysteroid dehydrogenase
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The carbonyl reductase activity exhibited by pig testicular 20β- hydroxysteroid dehydrogenase (20β-HSD) was examined using a recombinant enzyme. Kinetic parameters were obtained for 48 carbonyl group-containing substrates, including aromatic aldehydes, aromatic ketones, cycloketones, quinones, aliphatic aldehydes and aliphatic ketones. 20β-HSD showed a high affinity towards quinones, such as 9,10-phenanthrenequinone, α- naphthoquinone and menadione (K(m) values of 4, 2 and 5 μM, respectively), and the substrate utilization efficiency (V(max)/K(m)) of the enzyme against these quinones was very high. Cyclohexanone and 2-methylcyclohexanone were also reduced with a high V(max)/K(m) value, but not cyclopentanone or 2- methylcyclopentanone. Various aromatic aldehydes and ketones including benzaldehyde- and acetophenone-derivatives were reduced by 20β-HSD. Especially, 4-nitrobenzaldehyde and 4-nitroacetophenone were reduced with high V(max)/K(m) values in the related compounds. The enzyme also reduced the pyridine-derivatives, 2-, 3-, and 4-benzoylpyridine, with the V(max)/K(m) value for 2-benzoylpyridine being the highest. 20β-HSD reduced aliphatic aldehydes and aliphatic ketones, but was more effective on the former. The correlation between the structure of carbonyl compounds and their substrate V(max)/K(m) is discussed.
- Nakajin, Shizuo,Tamura, Fumihiro,Takase, Noriko,Toyoshima, Satoshi
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p. 1215 - 1218
(2007/10/03)
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- Effect of inhibitor or immobilization on reduction of benzoylpyridines by baker's yeast
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The stereochemical course of the reduction of benzolpyridine derivatives (1a-e) by baker's yeast can be modified by immobilization or by treating the reduction system with allyl alcohol or ethyl chloroacetate.
- Takemoto, Masumi,Yamamoto, Yuichi,Achiwa, Kazuo
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p. 853 - 855
(2007/10/03)
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- Synthesis of optically active α-phenylpyridylmethanols with cell cultures of Nicotiana tabacum
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We have synthesized optically active α-phenylpyridylmethanols by reduction or hydrolysis with cell cultures of Nicotiana tabacum or immobilized cells of N. tabacum.
- Takemoto,Moriyasu,Achiwa
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p. 1458 - 1461
(2007/10/03)
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- A novel hydroxyalkyl-decyanation of 4-pyridinecarbonitrile: A facile selective synthesis of 4-pyridinemethanols
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Reactions of 4-pyridinecarbonitrile with alkali metal and ketones or aldehydes provide a convenient and useful method for synthesis of 4-pyridinemethanols in good yields.
- Zeng,Cai,Gu
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p. 7275 - 7276
(2007/10/02)
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- Synthesis of optically active α-phenylpyridylmethanols with Baker's yeast
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We have synthesized optically active α-phenylpyridylmethanols by using free baker's yeast (FBY) in water, immobilized baker's yeast (IMBY) in water, and IMBY in hexane.
- Takemoto,Achiwa
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p. 802 - 805
(2007/10/02)
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- Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: Synthesis and monoamine oxidase catalyzed bioactivation
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Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.
- Efange,Michelson,Remmel,Boudreau,Dutta,Freshler
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p. 3133 - 3138
(2007/10/02)
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- PREPARATION OF PYRIDYL GRIGNARD REAGENTS AND CROSS COUPLING REACTIONS WITH SULFOXIDES BEARING AZAHETEROCYCLES
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Pyridyl Grignard reagents were prepared from the corresponding iodopyridine and EtMgBr.New cross coupling reactions of the Grignard reagents with azaheterocycles took place on the sulfinyl sulfur atom to afford biazaheteroaryls.
- Furukawa, Naomichi,Shibutani, Tadao,Fujihara, Hisashi
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p. 5845 - 5848
(2007/10/02)
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- REACTIONS OF PYRIDYL AND QUINOLYL SULFOXIDES WITH GRIGNARD REAGENT : A CONVENIENT PREPARATION OF PYRIDYL AND QUINOLYL GRIGNARD REAGENTS
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3-,4-Pyridyl and 4-quinolyl Grignard reagents were generated by the reaction of the corresponding phenyl sulfoxides with PhMgBr and give the adducts upon treatment with various aldehydes and ketones.The stereochemistry for the reaction was investigated.
- Furukawa, Naomichi,Shibutani, Tadao,Matsumura, Kazunori,Fujihara, Hisashi,Oae, Shigeru
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p. 3899 - 3902
(2007/10/02)
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- Zn/OH- REDUCTIONS OF ORGANIC COMPOUNDS IN DIMETHYLSULFOXIDE ; A NEW SIMPLE METHOD OF PREPARING RADICAL ANIONS
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A new method of preparing radical anions from a variety of organic substrates is proposed that involves the use of Zn/KOH in DMSO as electron source.
- Handoo, Kishan L.,Gadru, Kanchan
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p. 1371 - 1372
(2007/10/02)
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