- Nickel-catalyzed α-alkylation of ketones with benzyl alcohols
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We reported an efficient method for α-alkylation of ketones with benzyl alcohols using the pyridine-bridged pincer-type N-heterocyclic carbenes nickel complexes as catalysts. A wide range of ketones and benzyl alcohols were efficiently converted into various alkylated products in moderate to high yields. In addition, these nickel complexes were also successfully applied for the synthesis of a wide range of quinoline derivatives.
- Wu, Di,Wang, Yubin,Li, Min,Shi, Lei,Liu, Jichang,Liu, Ning
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- SmI2-mediated C-alkylation of Ketones with Alcohols under Microwave Conditions: A Novel Route to Alkylated Ketones
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A novel protocol is developed towards the preparation of alkylated ketones from alcohols in presence of catalytic amount of SmI2 and base with the elimination of water as a single by-product under microwave irradiation conditions. Furthermore, applicability of this methodology to the synthesis of Donepezil and late-stage functionalization in Pregnenolone is also reported. Successful application of this methodology in Friedl?nder quinolone synthesis using 2-aminobenzyl alcohol and various acetophenones expand the synthetic utility of this protocol.
- Gour, Jitendra,Kar, Swayamsiddha,Mahammad Ghouse, Shaik,Manohar Chelli, Sai,Nanduri, Srinivas,Pawar, Gaurav,Reddy Dannarm, Srinivas,Sonti, Rajesh
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- Novel bispidine-monoterpene conjugates—Synthesis and application as ligands for the catalytic ethylation of chalcones
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A number of new chiral bispidines containing monoterpenoid fragments have been ob-tained. The bispidines were studied as ligands for Ni-catalyzed addition of diethylzinc to chalcones. The conditions for chromatographic analysis by HPLC-UV were developed,
- Dalinger, Alexander I.,Kalinin, Mikhail A.,Kuranov, Sergey O.,Munkuev, Aldar A.,Okhina, Alina A.,Ottenbacher, Roman V.,Patrusheva, Oxana S.,Ponomarev, Konstantin Y.,Rogachev, Artem D.,Salakhutdinov, Nariman F.,Suslov, Evgeniy V.,Vatsadze, Sergey Z.,Volcho, Konstantin P.
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- Electrochemical-Induced Hydrogenation of Electron-Deficient Internal Olefins and Alkynes with CH3OH as Hydrogen Donor
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Efficient hydrogenation of electron-deficient internal olefins and alkynes access to saturate ketone with CH3OH as a single hydrogen donor under electrochemical conditions has been successfully developed. This hydrogenation strategy can be used to convert electron-deficient internal olefins and alkynes to saturate ketone under electrochemical conditions with exogenous-reductant and a metal catalyst. Mechanistic studies reveal that radical hydrogenation was involved in this transformation. Notably, various electron-deficient internal olefins and alkynes could be tolerated in such an electrochemical hydrogenation synthetic strategy and can be easily scaled up with good efficiency. (Figure presented.).
- Qin, Hongyun,Yang, Jianjing,Yan, Kelu,Xue, Yaxuan,Zhang, Meichen,Sun, Xuejun,Wen, Jiangwei,Wang, Hua
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supporting information
p. 2104 - 2109
(2021/03/15)
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- Neutral-eosin Y-catalyzed regioselective hydroacylation of aryl alkenes under visible-light irradiation
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Styrene derivatives were hydroacylated with exclusive anti-Markovnikov selectivity by using neutral eosin Y as a direct hydrogen-atom-transfer (HAT) catalyst under visible-light irradiation. Aldehydes and styrenes with various substituents were tolerated (>20 examples), giving the corresponding products in moderate to high yields. The key acyl radical intermediate was generated from a direct HAT process induced by photoexcited eosin Y. Subsequent addition to styrenes and a reverse HAT process generated the ketone products.
- Liu, Haiwang,Xue, Fei,Wang, Mu,Tang, Xinxin,Wu, Jie
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supporting information
p. 406 - 410
(2020/12/30)
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- Chemoselective reduction of ?,¢-unsaturated carbonyl and carboxylic compounds by hydrogen iodide
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The selective reduction of ?,¢-unsaturated carbonyl compounds was achieved to produce saturated carbonyl compounds with aqueous HI solution. The introduction of an aryl group at an ? or ¢ position efficiently facilitated the reduction with good yield. The reaction was applicable to compounds bearing carboxylic acids and halogen atoms. Through the investigation of the reaction mechanism, it was found that Michael-type addition of iodide occurred to produce ¢-iodo compounds followed by the reduction of C-I bond via anionic and radical paths.
- Matsumoto, Shoji,Marumoto, Hayato,Akazome, Motohiro,Otani, Yasuhiko,Kaiho, Tatsuo
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p. 590 - 599
(2021/03/29)
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- A Proton-Responsive Pyridyl(benzamide)-Functionalized NHC Ligand on Ir Complex for Alkylation of Ketones and Secondary Alcohols
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A Cp*Ir(III) complex (1) of a newly designed ligand L1 featuring a proton-responsive pyridyl(benzamide) appended on N-heterocyclic carbene (NHC) has been synthesized. The molecular structure of 1 reveals a dearomatized form of the ligand. The protonation of 1 with HBF4 in tetrahydrofuran gives the corresponding aromatized complex [Cp*Ir(L1H)Cl]BF4 (2). Both compounds are characterized spectroscopically and by X-ray crystallography. The protonation of 1 with acid is examined by 1H NMR and UV-vis spectra. The proton-responsive character of 1 is exploited for catalyzing α-alkylation of ketones and β-alkylation of secondary alcohols using primary alcohols as alkylating agents through hydrogen-borrowing methodology. Compound 1 is an effective catalyst for these reactions and exhibits a superior activity in comparison to a structurally similar iridium complex [Cp*Ir(L2)Cl]PF6 (3) lacking a proton-responsive pendant amide moiety. The catalytic alkylation is characterized by a wide substrate scope, low catalyst and base loadings, and a short reaction time. The catalytic efficacy of 1 is also demonstrated for the syntheses of quinoline and lactone derivatives via acceptorless dehydrogenation, and selective alkylation of two steroids, pregnenolone and testosterone. Detailed mechanistic investigations and DFT calculations substantiate the role of the proton-responsive ligand in the hydrogen-borrowing process.
- Kaur, Mandeep,U Din Reshi, Noor,Patra, Kamaless,Bhattacherya, Arindom,Kunnikuruvan, Sooraj,Bera, Jitendra K.
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supporting information
p. 10737 - 10748
(2021/06/15)
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- Iridium Complexes as Efficient Catalysts for Construction of α-Substituted Ketones via Hydrogen Borrowing of Alcohols in Water
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Ketones are of great importance in synthesis, biology, and pharmaceuticals. This paper reports an iridium complexes-catalyzed cross-coupling of alcohols via hydrogen borrowing, affording a series of α-alkylated ketones in high yield (86 %–95 %) and chemoselectivities (>99 : 1). This methodology has the advantages of low catalyst loading (0.1 mol%) and environmentally benign water as the solvent. Studies have shown the amount of base has a great impact on chemoselectivities. Meanwhile, deuteration experiments show water plays an important role in accelerating the reduction of the unsaturated ketones intermediates. Remarkably, a gram-scale experiment demonstrates this methodology of iridium-catalyzed cross-coupling of alcohols has potential application in the practical synthesis of α-alkylated ketones.
- Luo, Nianhua,Zhong, Yuhong,Wen, Huiling,Shui, Hongling,Luo, Renshi
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p. 1355 - 1364
(2021/03/03)
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- Application of 4, 6-dimethyl-2-mercaptopyrimidine bivalent nickel complex in preparation of [alpha]-alkyl ketone
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The invention relates to the field of metal organic chemistry, in particular to application of a 4, 6-dimethyl-2-mercaptopyrimidine bivalent nickel complex in preparation of [alpha]-alkyl ketone, which takes a 4, 6-dimethyl-2-mercaptopyrimidine nickel (II) compound as a catalyst and realizes selective preparation of [alpha]-alkyl ketone through cross-coupling reaction of secondary alcohol and primary alcohol by regulating and controlling reaction conditions. The coupling reaction is carried out in anhydrous toluene in the presence of alkali under the protection of inert gas. The application has the advantages of mild reaction system conditions and wide substrate applicability, and effectively avoids the use of organic phosphine ligands and noble metals.
- -
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Paragraph 0045-0046
(2021/04/07)
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- Tuning the Product Selectivity of the α-Alkylation of Ketones with Primary Alcohols using Oxidized Titanium Nitride Photocatalysts and Visible Light
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The direct α-alkylation of ketones with alcohol to synthesize important α-alkylated ketones and enones is an attractive procedure for C-C bond formation. High reaction temperatures are always needed for heterogeneous catalysis using non-noble metals, and switching product selectivity in one catalysis system remains a great challenge. In the present study, a visible-light-driven procedure for this reaction is proposed, using oxidized TiN photocatalysts under mild conditions, whereby the product selectivity can be well-tuned. Oxidized TiN photocatalysts with tunable surface N/O ratios were successfully synthesized through the facile and flexible thermal oxidation treatment of low-cost TiN nanopowder. The α-alkylation of acetophenone with benzyl alcohol to form the two important compounds chalcone and dihydrochalcone occurred even at room temperature and almost complete conversion was achieved at 100 °C under visible light. The proportion of the two products can be well-tuned by switching the surface N/O ratio of the synthesized photocatalysts. Visible light is demonstrated to affect the surface N/O ratio of the photocatalysts and contribute to tuning the product selectivity. Light intensity and action spectrum study proves that the generation of energetic charge carriers results in the observed activities under visible light, based on interband transitions of TiN or the ligand-to-metal charge transfer (LMCT) effect of the surface complex formed on TiO2. Thermal energy can be coupled with light energy within this photocatalytic system, which will facilitate the full use of solar energy. Different sequential reaction mechanisms on TiN and TiO2 are proposed to be responsible for the tunable product selectivity. The wide reaction scope, the fine conversion at a low light intensity, and the favorable reusability of photocatalysts prove the great application potential of this visible-light-driven procedure for the α-alkylation of ketones with primary alcohols.
- Li, Peifeng,Su, Haijia,Xiao, Gang,Zhao, Yilin
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p. 3640 - 3649
(2020/04/09)
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- Chemoselective Hydrosilylation of the α,β-Site Double Bond in α,β- And α,β,γ,δ-Unsaturated Ketones Catalyzed by Macrosteric Borane Promoted by Hexafluoro-2-propanol
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The B(C6F5)3-catalyzed chemoselective hydrosilylation of α,β- and α,β,γ,δ-unsaturated ketones into the corresponding non-symmetric ketones in mild reaction conditions is developed. Nearly 55 substrates including those bearing reducible functional groups such as alkynyl, alkenyl, cyano, and aromatic heterocycles are chemoselectively hydrosilylated in good to excellent yields. Isotope-labeling studies revealed that hexafluoro-2-propanol also served as a hydrogen source in the process.
- Zhan, Xiao-Yu,Zhang, Hua,Dong, Yu,Yang, Jian,He, Shuai,Shi, Zhi-Chuan,Tang, Lei,Wang, Ji-Yu
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p. 6578 - 6592
(2020/07/17)
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- Alkylation synthesis method of in-situ catalytic alcohol (by machine translation)
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The method comprises VIB metal complexes, an auxiliary ligand and a base as a catalytic reaction system, wherein the alcohol serves as an alkylating agent, and the nucleophilic substrate is subjected to in-situ catalytic alkylation reaction in a solvent and an inert gas atmosphere. The catalytic system has a wide application range on a substrate, can catalyze the synthesis of C-N and C-C bond compounds of different structures under mild conditions, and can green synthesize a series of valuable N - alkylation and C - alkylation compounds. (by machine translation)
- -
-
Paragraph 0099-0101; 0108-0110
(2020/11/01)
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- Phosphine-free pincer-ruthenium catalyzed biofuel production: High rates, yields and turnovers of solventless alcohol alkylation
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Phosphine-free pincer-ruthenium carbonyl complexes based on bis(imino)pyridine and 2,6-bis(benzimidazole-2-yl) pyridine ligands have been synthesized. For the β-alkylation of 1-phenyl ethanol with benzyl alcohol at 140 °C under solvent-free conditions, (Cy2NNN)RuCl2(CO) (0.00025 mol%) in combination with NaOH (2.5 mol%) was highly efficient (ca. 93% yield, 372?000 TON at 12?000 TO h-1). These are the highest reported values hitherto for a ruthenium based catalyst. The β-alkylation of various alcohol combinations was accomplished with ease which culminated to give 380?000 TON at 19?000 TO h-1 for the β-alkylation of 1-phenyl ethanol with 3-methoxy benzyl alcohol. DFT studies were complementary to mechanistic studies and indicate the β-hydride elimination step involving the extrusion of acetophenone to be the overall RDS. While the hydrogenation step is favored for the formation of α-alkylated ketone, the alcoholysis step is preferred for the formation of β-alkylated alcohol. The studies were extended for the upgradation of ethanol to biofuels. Among the pincer-ruthenium complexes based on bis(imino)pyridine, (Cy2NNN)RuCl2(CO) provided high productivity (335 TON at 170 TO h-1). Sterically more open pincer-ruthenium complexes such as (Bim2NNN)RuCl2(CO) based on the 2,6-bis(benzimidazole-2-yl) pyridine ligand demonstrated better reactivity and gave not only good ethanol conversion (ca. 58%) but also high turnovers (ca. 2100) with a good rate (ca. 710 TO h-1). Kinetic studies indicate first order dependence on concentration of both the catalyst and ethanol. Phosphine-free catalytic systems operating with unprecedented activity at a very low base loading to couple lower alcohols to higher alcohols of fuel and pharmaceutical importance are the salient features of this report. This journal is
- Das, Babulal,Das, Kanu,Kumar, Akshai,Srivastava, Hemant Kumar,Yasmin, Eileen
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p. 8347 - 8358
(2020/12/31)
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- Iodine-catalyzed α,β-dehydrogenation of ketones and aldehydes generating conjugated enones and enals
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A transition metal-free α,β-dehydrogenation of ketones and aldehydes was developed. This reaction was conducted in a facile I2/KI/DMSO system to produce the corresponding unsaturated compounds in good to high yields. The gram-scale experiment also indicated the potential synthetic value of this new reaction in organic synthesis. In the reaction, DMSO acted as both solvent and mild oxidant.
- Cao, Yuanjie,Chen, Tieqiao,Huang, Tianzeng,Liu, Long
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supporting information
p. 8697 - 8701
(2020/06/08)
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- Method for preparing alpha-alkyl substituted ketone compound
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The invention relates to a method for preparing an alpha-alkyl substituted ketone compound, which comprises the following steps: preparing a primary alcohol compound and a secondary alcohol compound as raw materials, adding alkali; with a cyclic iridium complex as a catalyst and water as a reaction medium, heating and stirring the mixture and reacting for 10 to 24 hours under the protection of inert gas, and cooling a reaction product to room temperature after the reaction is finished; carrying out reduced pressure distillation and concentration to obtain a crude product, and carrying out column chromatography purification to obtain a series of alpha alkyl substituted ketone compounds. The method is simple to operate, available in raw materials, low in price, high in reaction efficiency and selectivity, good in adaptability to various functional groups and wide in substrate universality; since water is used as a reaction medium to meet the green and environment-friendly requirements, the method is environmentally friendly and is carried out at gram level, so that the potential of industrially synthesizing the alpha alkyl substituted ketone compound is achieved; therefore, The method has expanded application in the fields of medicines, organic synthesis and the like.
- -
-
Paragraph 0101-0108
(2020/12/29)
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- Sustainable and Selective Alkylation of Deactivated Secondary Alcohols to Ketones by Non-bifunctional Pincer N-heterocyclic Carbene Manganese
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A sustainable and green route to access diverse functionalized ketones via dehydrogenative–dehydrative cross-coupling of primary and secondary alcohols is demonstrated. This borrowing hydrogen approach employing a pincer N-heterocyclic carbene Mn complex displays high activity and selectivity. A variety of primary and secondary alcohols are well tolerant and result in satisfactory isolated yields. Mechanistic studies suggest that this reaction proceeds via a direct outer-sphere mechanism and the dehydrogenation of the secondary alcohol substrates plays a vital role in the rate-limiting step.
- Lan, Xiao-Bing,Ye, Zongren,Liu, Jiahao,Huang, Ming,Shao, Youxiang,Cai, Xiang,Liu, Yan,Ke, Zhuofeng
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p. 2557 - 2563
(2020/05/04)
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- Proton-Coupled Electron Transfer: Transition-Metal-Free Selective Reduction of Chalcones and Alkynes Using Xanthate/Formic Acid
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Highly chemoselective reduction of α,β-unsaturated ketones to saturated ketones and stereoselective reduction of alkynes to (E)-alkenes has been developed under a transition-metal-free condition using a xanthate/formic acid mixture through proton-coupled electron transfer (PCET). Mechanistic experiments and DFT calculations support the possibility of a concerted proton electron-transfer (CPET) pathway. This Birch-type reduction demonstrates that a small nucleophilic organic molecule can be used as a single electron-transfer (SET) reducing agent with a proper proton source.
- Prasanna, Ramanathan,Guha, Somraj,Sekar, Govindasamy
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supporting information
p. 2650 - 2653
(2019/04/17)
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- Aldehydes as Alkylating Agents for Ketones
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Common and non-toxic aldehydes are proposed as reagents for alkylation of ketones instead of carcinogenic alkyl halides. The developed reductive alkylation reaction proceeds in the presence of the commercially available ruthenium catalyst [(cymene)RuCl2]2 (as low as 250 ppm) and carbon monoxide as the reducing agent. The reaction works well for a broad substrate scope, including aromatic and aliphatic aldehydes and ketones. It can be carried out without a solvent and often gives nearly quantitative yields of the products. This straightforward and cost-effective method is promising not only for laboratory application but also for industry, which produces carbon monoxide as a large-scale waste product.
- Runikhina, Sofiya A.,Afanasyev, Oleg I.,Biriukov, Klim,Perekalin, Dmitry S.,Klussmann, Martin,Chusov, Denis
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p. 16225 - 16229
(2019/11/22)
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- A Radical Approach to Anionic Chemistry: Synthesis of Ketones, Alcohols, and Amines
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Historically accessed through two-electron, anionic chemistry, ketones, alcohols, and amines are of foundational importance to the practice of organic synthesis. After placing this work in proper historical context, this Article reports the development, f
- Ni, Shengyang,Padial, Natalia M.,Kingston, Cian,Vantourout, Julien C.,Schmitt, Daniel C.,Edwards, Jacob T.,Kruszyk, Monika M.,Merchant, Rohan R.,Mykhailiuk, Pavel K.,Sanchez, Brittany B.,Yang, Shouliang,Perry, Matthew A.,Gallego, Gary M.,Mousseau, James J.,Collins, Michael R.,Cherney, Robert J.,Lebed, Pavlo S.,Chen, Jason S.,Qin, Tian,Baran, Phil S.
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p. 6726 - 6739
(2019/05/06)
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- C?C Bond Formation of Benzyl Alcohols and Alkynes Using a Catalytic Amount of KOtBu: Unusual Regioselectivity through a Radical Mechanism
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We report a C?C bond-forming reaction between benzyl alcohols and alkynes in the presence of a catalytic amount of KOtBu to form α-alkylated ketones in which the C=O group is located on the side derived from the alcohol. The reaction proceeds under thermal conditions (125 °C) and produces no waste, making the reaction highly atom efficient, environmentally benign, and sustainable. Based on our mechanistic investigations, we propose that the reaction proceeds through radical pathways.
- Kumar, Amit,Janes, Trevor,Chakraborty, Subrata,Daw, Prosenjit,von Wolff, Niklas,Carmieli, Raanan,Diskin-Posner, Yael,Milstein, David
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supporting information
p. 3373 - 3377
(2019/02/14)
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- Nonbifunctional Outer-Sphere Strategy Achieved Highly Active α-Alkylation of Ketones with Alcohols by N-Heterocyclic Carbene Manganese (NHC-Mn)
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The unusual nonbifunctional outer-sphere strategy was successfully utilized in developing an easily accessible N-heterocyclic carbene manganese (NHC-Mn) system for highly active α-alkylation of ketones with alcohols. This system was efficient for a wide range of ketones and alcohols under mild reaction conditions, and also for the green synthesis of quinoline derivatives. The direct outer-sphere mechanism and the high activity of the present system demonstrate the potential of nonbifunctional outer-sphere strategy in catalyst design for acceptorless dehydrogenative transformations.
- Lan, Xiao-Bing,Ye, Zongren,Huang, Ming,Liu, Jiahao,Liu, Yan,Ke, Zhuofeng
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supporting information
p. 8065 - 8070
(2019/10/11)
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- Controlling the selectivity and efficiency of the hydrogen borrowing reaction by switching between rhodium and iridium catalysts
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The catalytic alkylation of ketones with alcohols via the hydrogen borrowing methodology (HB) has the potential to be a highly efficient approach for forming new carbon-carbon bonds. However, this transformation can result in more than one product being formed. The work reported here utilises bidentate triazole-carbene ligated iridium and rhodium complexes as catalysts for the selective formation of alkylated ketone or alcohol products. Switching from an iridium centre to a rhodium centre in the complex resulted in significant changes in product selectivity. Other factors-base, base loading, solvent and reaction temperature-were also investigated to tune the selectivity further. The optimised conditions were used to demonstrate the scope of the reaction across 17 ketones and 14 alcohols containing a variety of functional groups. A series of mechanistic investigations were performed to probe the reasons behind the product selectivity, including kinetic and deuterium studies.
- Wang, Danfeng,McBurney, Roy T.,Pernik, Indrek,Messerle, Barbara A.
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supporting information
p. 13989 - 13999
(2019/10/01)
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- The α-alkylation of ketones with alcohols in pure water catalyzed by a water-soluble Cp?Ir complex bearing a functional ligand
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A water-soluble dinuclear Cp?Ir complex bearing 4,4′,6,6′-tetrahydroxy-2,2′-bipyrimidine as a bridging ligand was found to be a highly effective catalyst for the α-alkylation of ketones with alcohols in pure water. In the presence of catalyst (0.5 mol%), a series of desirable products were obtained with high reaction economy under environmentally benign conditions. The importance of the hydroxy group in the ligand for catalytic hydrogen transfer was confirmed by mechanism experiments. Furthermore, the application of this catalytic system for the synthesis of a biologically active molecule donepezil in pure water has been accomplished. Notably, this research would facilitate the progress of C-C bond-forming reactions in water catalyzed by water-soluble metal-ligand bifunctional catalysts.
- Meng, Chong,Xu, Jing,Tang, Yawen,Ai, Yao,Li, Feng
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p. 14057 - 14065
(2019/09/18)
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- Nickel-Catalyzed Alkylation of Ketone Enolates: Synthesis of Monoselective Linear Ketones
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Herein we have developed a Ni-catalyzed protocol for the synthesis of linear ketones. Aryl, alkyl, and heteroaryl ketones as well as alcohols yielded the monoselective ketones in up to 90% yield. The catalytic protocol was successfully applied in to a gram-scale synthesis. For a practical utility, applications of a steroid derivative, oleyl alcohol, and naproxen alcohol were employed. Preliminary catalytic investigations involving the isolation of a Ni intermediate and defined Ni-H species as well as a series of deuterium-labeling experiments were performed.
- Das, Jagadish,Vellakkaran, Mari,Banerjee, Debasis
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p. 769 - 779
(2019/01/24)
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- Ruthenium-Catalyzed β-Alkylation of Secondary Alcohols and α-Alkylation of Ketones via Borrowing Hydrogen: Dramatic Influence of the Pendant N-Heterocycle
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Three bidentate ruthenium(II) complexes with a pyridonate fragment were prepared and fully characterized. These complexes are structurally similar, but differ in their pendant substituents. Complex 1 contains a phenyl unit, whereas complexes 2 and 3 have uncoordinated thienyl and thiazolyl groups, respectively. These complexes were tested as catalysts for β-alkylation of secondary alcohols with primary alcohols, and 3 shows the highest activity, suggesting the thiazolyl ring participates in the catalytic process. Furthermore, 3 is an excellent catalyst for α-alkylation of ketones with primary alcohols. Various α-alkylated ketones were synthesized in high yields, by using 0.05 mol % 3 and 0.25 equiv of t-BuOK within 30 min.
- Zhang, Chong,Zhao, Jiong-Peng,Hu, Bowen,Shi, Jing,Chen, Dafa
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p. 654 - 664
(2019/02/17)
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- Palladium on carbon-catalyzed Α-alkylation of ketones with alcohols as electrophiles: Scope and mechanism
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The α-alkylation of ketones with alcohols represents a green strategy for the formation of crucial carbon–carbon bonds since it only produces water as byproduct. In terms of reaction mechanism, the evidence for homogeneous catalysis supports a catalytic hydrogen-borrowing pathway; however, the reaction mechanism has not been investigated for heterogeneous Pd/C catalysts. Here, we report an improved method for α-alkylation of ketones with alcohols using commercially available Pd/C, ubiquitous in organic synthesis labs, as catalyst. The reaction conditions are mild compared to state-of-the-art for both homo- and heterogeneous catalysts, and the developed conditions produces quantitative yields for most ketones and alcohols. A hot filtration experiment and recycling of the catalyst supports the heterogeneous nature of catalysis. Importantly, the reaction mechanism is studied for the first time by a combination of stoichiometric experiments and kinetic analyses by in-situ IR (React-IR).
- Bennedsen, Niklas R.,Mortensen, Rasmus L.,Kramer, S?ren,Kegn?s, S?ren
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p. 153 - 160
(2019/02/14)
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- Reaction condition controlled nickel(ii)-catalyzed C-C cross-coupling of alcohols
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The challenge in the C-C cross-coupling of secondary and primary alcohols using acceptorless dehydrogenation coupling (ADC) is the difficulty in accurately controlling product selectivities. Herein, we report a controlled approach to a diverse range of β-alkylated secondary alcohols, α-alkylated ketones and α,β-unsaturated ketones using the ADC methodology employing a Ni(ii) 4,6-dimethylpyrimidine-2-thiolate cluster catalyst under different reaction conditions. This catalyst could tolerate a wide range of substrates and exhibited a high activity for the annulation reaction of secondary alcohols with 2-aminobenzyl alcohols to yield quinolines. This work is an example of precise chemoselectivity control by careful choice of reaction conditions.
- Zhang, Meng-Juan,Li, Hong-Xi,Young, David J.,Li, Hai-Yan,Lang, Jian-Ping
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supporting information
p. 3567 - 3574
(2019/04/14)
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- Selective Ketone Formations via Cobalt-Catalyzed β-Alkylation of Secondary Alcohols with Primary Alcohols
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A homogeneous cobalt-catalyzed β-alkylation of secondary alcohols with primary alcohols to selectively synthesize ketones via acceptorless dehydrogenative coupling is reported for the first time. Notably, this transformation is environmentally benign and atom economical with water and hydrogen gas as the only byproducts.
- Pandey, Bedraj,Xu, Shi,Ding, Keying
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supporting information
p. 7420 - 7423
(2019/10/02)
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- Catalyst-free chemoselective conjugate addition and reduction of α,β-unsaturated carbonyl compounds: Via a controllable boration/protodeboronation cascade pathway
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A novel, efficient transition-metal-free and controllable boration/protodeboronation strategy has been developed for the chemoselective conjugate addition and 1,4-reduction of α,β-unsaturated carbonyl compounds. Without any metal-catalyst or base, a series of β-boration products of α,β-unsaturated carbonyl compounds was easily obtained in moderate to excellent yields in a mixed solvent of ethanol and water. The presence of a catalytic amount of Cs2CO3 can effectively induce further protodeboronation reaction towards 1,4-reduction products at higher reaction temperature. Therefore, by slightly changing the reaction conditions, the boration or reduction products of α,β-unsaturated carbonyl compounds can be controllably obtained. Mechanistic studies revealed that Cs2CO3 played the key role in activating the protodeboronation step. This transition-metal-catalyst-free and product controllable method provides a useful and eco-friendly tool for the highly chemoselective preparation of the β-boration products and 1,4-reduction products of α,β-unsaturated carbonyl compounds.
- Huang, Xi,Hu, Junjie,Wu, Mengying,Wang, Jiayi,Peng, Yanqing,Song, Gonghua
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p. 255 - 260
(2018/01/12)
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- Transition-Metal-Free Highly Chemoselective and Stereoselective Reduction with Se/DMF/H2O System
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A novel metal-free reduction system, in which H2Se (or HSe-) produced in situ from Se/DMF/H2O acts as the active reducing species, has been developed. By using water as an inexpensive, safe, and environmentally friendly surrogate as the hydrogen donor, this new reduction system incorporating Se/DMF/H2O displayed high selectivity and good activity in the reduction of α,β-unsaturated ketones and alkynes. Therefore, this reduction system has great potential to be a general and practical reduction methodology in organic transformation.
- Li, Hong-Chen,An, Cui,Wu, Ge,Li, Guo-Xing,Huang, Xiao-Bo,Gao, Wen-Xia,Ding, Jin-Chang,Zhou, Yun-Bing,Liu, Miao-Chang,Wu, Hua-Yue
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supporting information
p. 5573 - 5577
(2018/09/12)
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- Dirhodium(ii)/P(t-Bu)3 catalyzed tandem reaction of α,β-unsaturated aldehydes with arylboronic acids
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Phosphine ligated dirhodium(ii) acetate is advocated as a catalyst for the synthesis of aryl alkyl ketones by the tandem reaction of α,β-unsaturated aromatic or aliphatic aldehydes with arylboronic acids. This tandem procedure included arylation followed by the isomerization reaction. This method exhibits good functional group tolerance and has a broad substrate scope. With the conjugated aldehydes, the one-step synthesis of γ,δ-unsaturated ketones was realized through this reaction. It is noteworthy that the length of the Rh-P bond is an important factor affecting catalytic reactions. The comparative analysis of the crystal structures of axially alkylphosphane and arylphosphane ligated dirhodium(ii) acetate revealed that the shorter Rh-P bond length favors the isomerization process as compared to the longer one. In addition, the dirhodium(ii) compound can be recovered after the completion of the reaction.
- Ma, Ziling,Wang, Yuanhua
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supporting information
p. 7470 - 7476
(2018/10/24)
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- Manganese-Catalyzed α-Alkylation of Ketones, Esters, and Amides Using Alcohols
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Herein we report the manganese-catalyzed C-C bond-forming reactions via α-alkylation of ketones, amides, and esters, using primary alcohols. β-Alkylation of secondary alcohols by primary alcohols to obtain α-alkylated ketones is also reported. The reactions are catalyzed by a (iPr-PNP)Mn(H)(CO)2 pincer complex under mild conditions in the presence of (catalytic) base liberating water (and H2 in the case of secondary alcohol alkylation) as the sole byproduct.
- Chakraborty, Subrata,Daw, Prosenjit,Ben David, Yehoshoa,Milstein, David
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p. 10300 - 10305
(2018/10/20)
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- NNN pincer Ru(II)-complex-catalyzed α-alkylation of ketones with alcohols
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A series of novel ruthenium(II) complexes supported by a symmetrical NNN ligand were prepared and fully characterized. These complexes exhibited good performance in transfer hydrogenation to form new C-C bonds using alcohols as the alkylating agents, generating water as the only byproduct. A broad range of substrates, including (hetero)aryl- or alkyl-ketones and alcohols, were well tolerated under the optimized conditions. Notably, α-substituted methylene ketones were also investigated, which afforded α-branched steric hindrance products. A potential application of α-alkylation of methylene acetone to synthesize donepezil was demonstrated, which provided the desired product in 83% yield. Finally, this catalytic system could be applied to a one-pot double alkylation procedure with sequential addition of two different alcohols. The current protocol is featured with several characteristics, including a broad substrate scope, low catalyst (0.50 mol %) loadings, and environmental benignity.
- Cao, Xiao-Niu,Wan, Xiao-Min,Yang, Fa-Liu,Li, Ke,Hao, Xin-Qi,Shao, Tian,Zhu, Xinju,Song, Mao-Ping
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p. 3657 - 3668
(2018/04/14)
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- Solvent-free direct α-alkylation of ketones by alcohols catalyzed by nickel supported on silica-alumina
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The α-alkylation of acetophenone with benzyl alcohol through borrowing hydrogen has been studied using nickel catalysis. Ni/SiO2-Al2O3 was found to be the best catalyst for this transformation and the corresponding alkylated acetophenone was obtained with 93% isolated yield. Following the objectives of clean and sustainable chemistry, the reaction occurs under solvent-free conditions and requires only a catalytic amount of base. This protocol was next applied to a wide range of ketones and alcohols and the desired products were isolated with 18-86% yields (26 examples). The recovery and recyclability of the nickel catalyst was also investigated and it was found to be active over 5 runs without significant loss of activity. Surprisingly, the active catalyst appears to include an amorphous nickel hydroxide layer.
- Charvieux, Aubin,Giorgi, Javier B.,Duguet, Nicolas,Métay, Estelle
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supporting information
p. 4210 - 4216
(2018/10/02)
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- Photoredox-Catalyzed Hydroacylation of Olefins Employing Carboxylic Acids and Hydrosilanes
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A hydroacylation reaction of alkenes has been achieved employing readily available carboxylic acids as the acyl source and hydrosilanes as a hydrogen source via photoredox catalysis. The combination of both single electron transfer and hydrogen atom transfer steps has dramatically expanded new applications of carboxylic acids in organic synthesis. The protocol also features extremely mild conditions, broad substrate scope, and good functional group tolerance, affording a novel and convenient approach to hydroacylation of alkenes.
- Zhang, Muliang,Ruzi, Rehanguli,Xi, Junwei,Li, Nan,Wu, Zhongkai,Li, Weipeng,Yu, Shouyun,Zhu, Chengjian
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supporting information
p. 3430 - 3433
(2017/07/15)
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- Ruthenium phosphine-pyridone catalyzed cross-coupling of alcohols to form α-alkylated ketones
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An efficient and green route to access diverse functionalized ketones via dehydrogenative-dehydrative cross-coupling of primary and secondary alcohols is demonstrated. Selective and tunable formation of ketones or alcohols is catalyzed by a recently developed proton responsive ruthenium phosphine-pyridone complex. Light alcohols such as ethanol could be used as alkylating agents in this methodology. Moreover, selective tandem double alkylation of isopropanol is achieved by sequential addition of different alcohols.
- Sahoo, Apurba R.,Lalitha, Gummidi,Murugesh,Bruneau, Christian,Sharma, Gangavaram V.M.,Suresh, Surisetti,Achard, Mathieu
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p. 10727 - 10731
(2018/05/31)
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- Use of a Cyclometalated Iridium(III) Complex Containing a N∧C∧N-Coordinating Terdentate Ligand as a Catalyst for the α-Alkylation of Ketones and N-Alkylation of Amines with Alcohols
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A cyclometalated iridium(III) complex containing a N∧C∧N-coordinating terdentate ligand [Ir(dpyx-N,C,N)Cl(μ-Cl)]2 was found to be a general and highly effective catalyst for the α-alkylation of ketones and N-alkylation of amines with alcohols. In the presence of catalyst (1 mol % Ir) and base (0.2-0.5 equiv), a variety of desirable products were obtained in good yields under an air atmosphere. Notably, this research exhibited the new potential of Ir(III) complexes bearing non-Cp? ligand and will facilitate the progress of the hydrogen autotransfer process.
- Liu, Pengcheng,Liang, Ran,Lu, Lei,Yu, Zhentao,Li, Feng
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p. 1943 - 1950
(2017/02/26)
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- Method for synthesizing alpha-alkyl ketone under catalysis of iridium
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The invention discloses a method for synthesizing alpha-alkyl ketone under catalysis of iridium. The method comprises steps as follows: ketone, an alcohol compound, a iridium complex catalyst, alkali and a solvent, namely, tert-amyl alcohol are added to a reaction container, the reaction mixture is subjected to a reflux reaction in the air and cooled to the room temperature after the reaction ends, a solvent is removed through rotary evaporation, and a target compound is obtained through column separation. A tridentate iridium complex with an N^C^N ligand is used, all that is required is to add 0.2 equivalents of carbonate during the reaction in the air, the reaction takes only 10-12 h, and remarkable advantages are shown. Therefore, the reaction meets the green chemistry requirement, and broad development prospect is realized.
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Paragraph 0029; 0030; 0031; 0032; 0033
(2017/07/12)
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- Method for synthesizing alpha-alkyl ketone
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The invention discloses a method for synthesizing alpha-alkyl ketone, and especially includes the following steps of: in a reaction vessel, adding secondary alcohol, a transition metal catalyst, and a solvent tertiary amyl alcohol; and heating and refluxing a reaction mixture in an oil bath for several hours, cooling the mixture to a room temperature; then adding primary alcohol and alkali, heating and refluxing the reaction mixture for several hours, and then obtaining a target compound through column separation. The method for synthesizing the alpha-alkyl ketone starts from the primary alcohol and the secondary alcohol. With the participation of the transition metal catalyst, the alpha-alkyl ketone is generated through a serial secondary alcohol non-acceptor dehydrogenation oxidation reaction/alpha-alkylation reaction of ketone. The reaction shows three obvious advantages that 1) non-toxic alcohols are used as the starting materials; 2) only hydrogen and water are generated in the reaction without environmental hazards; 3) atomic economy is high in the reaction; and 4) only 0.1 equivalents of carbonate is needed for the reaction, and the reaction only takes 3-6 hours. Therefore, the reaction meets the requirements of green chemistry and has broad development prospects.
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Paragraph 0058; 0059; 0060; 0061; 0062
(2017/04/12)
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- Compounding method for beta-aryl propiophenone compound
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The invention discloses a compounding method for a beta-aryl propiophenone compound. The compounding method is characterized by taking chalcone compounds as reaction substrates, and selectively chemically reducing the carbon-carbon double bonds in the rea
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Paragraph 0087-0090
(2018/03/01)
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- A method for synthesis of α-alkyl ketone
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The invention discloses a method for synthesizing alpha-alkyl ketone. The method comprises the following steps: adding alkyne, [(IPr)AuCl], AgOTf, 1,4-dioxane and water in a reaction container, performing microwave reaction on a reaction mixture for 1h at 120 DEG C and cooling to room temperature; further adding [Cp*IrCl2]2, alkali and alcohol into the reaction mixture, performing microwave reaction on the reaction mixture for 2h at 130 DEG C and cooling to room temperature; filtering, performing rotary evaporation to remove a solvent, and then separating by a column to obtain a target compound. The method disclosed by the invention is started from chemical raw materials which are easy to obtain, namely alkyne, water and alcohol, alpha-alkyl ketone is obtained under the participation of gold and iridium catalysts, and the reaction only generates water as a byproduct. Therefore, the reaction is in line with the requirements of green chemistry and has broad development prospects.
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Paragraph 0046; 0047; 0048; 0049
(2016/11/28)
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- Transition-Metal-Free Synthesis of Homo- and Hetero-1,2,4-Triaryl Benzenes by an Unexpected Base-Promoted Dearylative Pathway
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An unprecedented approach for the synthesis of homo- and hetero-1,2,4-triaryl benzenes has been developed using a simple base-mediated reaction of either α-aryl cinnamyl alcohols or α,γ-di-aryl propanones. The salient feature of this strategy involves the sequential hydride transfer, regiospecific condensation, regiospecific dearylation, and aromatization under metal-free reaction conditions. The synthesis of unsymmetrically substituted triphenylenes by oxidative coupling of the synthesized 1,2,4-triaryl benzenes has also been demonstrated.
- Rehan, Mohammad,Maity, Sanjay,Morya, Lalit Kumar,Pal, Kaushik,Ghorai, Prasanta
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p. 7728 - 7732
(2016/07/07)
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- 2,4,5-Trisubstituted thiazole derivatives as HIV-1 NNRTIs effective on both wild-type and mutant HIV-1 reverse transcriptase: Optimization of the substitution of positions 4 and 5
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In our previous work, novel 2,4,5-trisubstituted thiazole derivatives (TSTs) were synthesized, and their activities were evaluated against HIV-1 reverse transcriptase. Some interesting results were obtained, which led us to a new discovery regarding these TSTs. In the present study, 21 new 2,4,5-trisubstituted thiazole derivatives were rationally designed and synthesized as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) in accordance with our previous study. Among the synthesized target compounds, compounds 14, 16, 17, and 19 showed more potent inhibitory activities against HIV-1 with an IC50value of 0.010?μM. Compounds 4, 9, 10, 11, 13 and 16 were further tested on nine NNRTI-resistant HIV-1 strains, and all of these compounds exhibited inhibitory effects. A molecular docking study was conducted, and the results showed a consistent and stable binding mode for the typical compounds. These results have provided deeper insights and SAR of these types of NNRTIs.
- Xu, Zhongliang,Guo, Jiamei,Yang, Ying,Zhang, Mengdi,Ba, Mingyu,Li, Zhenzhong,Cao, Yingli,He, Ricai,Yu, Miao,Zhou, Hua,Li, Xiaoxi,Huang, Xiaoshan,Guo, Ying,Guo, Changbin
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p. 309 - 316
(2016/08/04)
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- Borylation and selective reduction of α,β-unsaturated ketones under mild conditions catalyzed by Cu nanoparticles
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An effective strategy for synthesis of Cu nanoparticles is designed, these nanoparticles have high catalytic activity in conjugate addition of B2(pin)2and α,β-unsaturated ketones. The reaction of protodeboration can proceed with adding NaOtBu. In this way, a new method to reduce the conjugated alkenes of α,β-unsaturated ketones is developed with organoboranes as intermediates. Cu nanocrystals also have excellent performance in gram-scale reaction and recycling experiment. A possible mechanism is proposed.
- Zhou, Xin-Feng,Sun, Yu-Yang,Wu, Ya-Dong,Dai, Jian-Jun,Xu, Jun,Huang, Yu,Xu, Hua-Jian
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p. 5691 - 5698
(2016/08/23)
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- Bifunctional Ru(II) complex catalysed carbon-carbon bond formation: an eco-friendly hydrogen borrowing strategy
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The atom economical borrowing hydrogen methodology enables the use of alcohols as alkylating agents for selective C-C bond formation. A bifunctional 2-(2-pyridyl-2-ol)-1,10-phenanthroline (phenpy-OH) based Ru(ii) complex (2) was found to be a highly efficient catalyst for the one-pot β-alkylation of secondary alcohols with primary alcohols and double alkylation of cyclopentanol with different primary alcohols. Exploiting the metal-ligand cooperativity in complex 2, several aromatic, aliphatic and heteroatom substituted alcohols were selectively cross-coupled in high yields using significantly low catalyst loading (0.1 mol%). An outer-sphere mechanism is proposed for this system as exogenous PPh3 has no significant effect on the rate of the reaction. Notably, this is a rare one-pot strategy for β-alkylation of secondary alcohols using a bifunctional Ru(ii)-complex. Moreover, this atom-economical methodology displayed the highest cumulative turn over frequency (TOF) among all the reported transition metal complexes in cross coupling of alcohols.
- Chakrabarti, Kaushik,Paul, Bhaskar,Maji, Milan,Roy, Bivas Chandra,Shee, Sujan,Kundu, Sabuj
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p. 10988 - 10997
(2016/12/06)
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- Bifunctional RuII-Complex-Catalysed Tandem C?C Bond Formation: Efficient and Atom Economical Strategy for the Utilisation of Alcohols as Alkylating Agents
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Catalytic activities of a series of functional bipyridine-based RuIIcomplexes in β-alkylation of secondary alcohols using primary alcohols were investigated. Bifunctional RuIIcomplex (3 a) bearing 6,6’-dihydroxy-2,2’-bipyridine (6DHBP) ligand exhibited the highest catalytic activity for this reaction. Using significantly lower catalyst loading (0.1 mol %) dehydrogenative carbon?carbon bond formation between numerous aromatic, aliphatic and heteroatom substituted alcohols were achieved with high selectivity. Notably, for the synthesis of β-alkylated secondary alcohols this protocol is a rare one-pot strategy using a metal–ligand cooperative RuIIsystem. Remarkably, complex 3 a demonstrated the highest reactivity compared to all the reported transition metal complexes in this reaction.
- Roy, Bivas Chandra,Chakrabarti, Kaushik,Shee, Sujan,Paul, Subhadeep,Kundu, Sabuj
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supporting information
p. 18147 - 18155
(2016/12/16)
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- Method for synthesizing alpha-alkyl ketone
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The invention discloses a method for synthesizing alpha-alkyl ketone. The method comprises the following steps: adding ketone, a compound alcohol, an iridium complex catalyst, an alkali and a solvent tert-amyl alcohol in a reaction container, carrying out a refluxing reaction on the above obtained reaction mixture in air for several hours, cooling the obtained reaction product to room temperature, carrying out rotary evaporation to remove the solvent, and carrying out column separation to obtain the target compound. The meta-organic bifunctional iridium complex is used, only 0.1 equivalent carbonate is added in the reaction process, and the reaction is carried in air for 6h, so obvious advantages are displayed; and the reaction accords with green chemistry requirements, and has wide development prospect.
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Paragraph 0045; 0046; 0047; 0048; 0049
(2016/10/07)
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- Iron-Catalyzed α-Alkylation of Ketones with Alcohols
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A general and benign iron-catalyzed α-alkylation reaction of ketones with primary alcohols has been developed. The key to success of the reaction is the use of a Kn?lker-type complex as catalyst (2 mol %) in the presence of Cs2CO3 as base (10 mol %) under hydrogen-borrowing conditions. Using 2-aminobenzyl alcohol as alkylation reagent allows for the "green" synthesis of quinoline derivatives.
- Elangovan, Saravanakumar,Sortais, Jean-Baptiste,Beller, Matthias,Darcel, Christophe
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supporting information
p. 14483 - 14486
(2016/01/25)
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- Transition-Metal-Free Self-Hydrogen-Transferring Allylic Isomerization
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Phenanthroline and tert-butoxide have been established as powerful radical initiators in reactions such as the SRN1-type coupling reactions due to the cooperation of large heteroarenes and a special feature of tert-butoxide. The first phenanthroline-tert-butoxide-catalyzed transition-metal-free allylic isomerization is described. The resulting ketones are key intermediates for indenes. The control experiments rule out the base-promoted allylic anion pathway. The radical pathway is supported by experimental evidence that includes kinetic study, kinetic isotope effect, isotope-labeling experiments, trapping experiments, and EPR experiments.
- Zheng, Hong-Xing,Xiao, Zu-Feng,Yao, Chuan-Zhi,Li, Qiang-Qiang,Ning, Xiao-Shan,Kang, Yan-Biao,Tang, Yong
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p. 6102 - 6105
(2016/01/09)
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- Cobalt-catalyzed intermolecular hydroacylation of olefins through chelation-assisted imidoyl C-H activation
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A low-valent cobalt catalyst generated from cobalt(II) bromide, a diphosphine ligand, and zinc powder promotes intermolecular hydroacylation of olefins using N-3-picolin-2-yl aldimines as aldehyde equivalents, which affords, upon acidic hydrolysis, ketone products in moderate to good yields with high linear selectivity. The reaction is applicable to styrenes, vinylsilanes, and aliphatic olefins as well as to various aryl and heteroaryl aldimines. The cobalt catalysis features a distinctively lower reaction temperature (60 °C) compared with those required for the same type of transformations catalyzed by rhodium complexes (typically 130-150°C).
- Yang, Junfeng,Seto, Yuan Wah,Yoshikai, Naohiko
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p. 3054 - 3057
(2015/05/20)
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