Synthesis of enantiopure (R)-(−)-massoialactone through ruthenium-SYNPHOS asymmetric hydrogenation

Total synthesis of enantiopure (R)-(−)-massoialactone was achieved. The key step includes the asymmetric hydrogenation of an achiral β-keto ester using a ruthenium-SYNPHOS^® catalyst to set the hydroxyl function in a stereocontrolled manner with excellent enantioselectivity (>99% ee). Ring closing metathesis (RCM) in the presence of Grubbs’ catalyst allows the final construction of the six-membered lactone.     

液相色谱/质谱联机研究还原烷基化合成3-(β-羟乙基砜基)N-乙基苯胺的反应历程

 3 (β 羟乙基砜基 )苯胺在催化剂镍的存在下与醛发生加氢反应 ,可直接制得 3 (β 羟乙基砜基 )N 乙基苯胺。运用高效液相色谱 /质谱联机系统对反应生成的中间产物进行分析 ,研究了加氢还原烷基化反应的历程。     

An enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid via asymmetric hydrogenation

A concise enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (1, Pregabalin) has been developed. The key step is the asymmetric hydrogenation of a 3-cyano-5-methylhex-3-enoic acid salt 2 with a rhodium Me-DuPHOS catalyst, providing the desired (S)-3-cyano-5-methylhexanoate 3 in very high ee. Subsequent hydrogenation of the nitrile 3 with a heterogeneous nickel catalyst provides Pregabalin 1 in excellent overall yield and purity.     

铱催化 3-羟甲基-2H-苯并吡喃类化合物的不对称氢化

从(1R,2S)-环己烷吡啶醇出发,合成了具有不同轴手性的反式环己烷骨架铱络合物,并将其应用于3-羟甲基-2H-苯并吡喃的不对称氢化中.结果表明,当以Ir-8为催化剂,二氯甲烷为溶剂,氢气压力5MPa,室温反应16h时,可以取得极好的反应活性,产物最高对映选择性可达94%.     

An efficient enantioselective synthesis of (S)-(-)-acromelobic acid

[reaction: see text] A highly efficient enantioselective synthesis of (S)-(-)-acromelobic acid (1) was achieved via asymmetric hydrogenation of dehydroamino acid derivative (3) using (R,R)-[Rh(DIPAMP)(COD)]BF(4) catalyst followed by removal of protective groups in >98% ee and good over all yield. The key intermediate (3) was prepared from the commercially available citrazinic acid (4) in six steps.     

Synthesis of enantiopure (R)-2-(4-methoxy-3-(3-methoxypropoxy)-benzyl)-3-methylbutanoic acid—a key intermediate for the preparation of Aliskiren

The enantioselective hydrogenation of (E)-2-(4-methoxy-3-(3-methoxypropoxy)-benzylidene)-3-methylbutanoic acid (1) to (R)-2-(4-methoxy-3-(3-methoxypropoxy)-benzyl)-3-methylbutanoic acid (2)—a key intermediate in the synthesis of the pharmacologically important renin inhibitor Aliskiren—is described. The stereochemistry of the catalytic transformation has been studied using a number of homogeneous chiral Rh(I) and Ru(II) complexes bearing ferrocene-based phosphine ligands. The highest enantioselectivity for the homogeneous hydrogenation of 1 (up to 95% ee) was achieved with a [Rh(NBD)₂]BF₄ pre-catalyst (substrate/catalyst ratio 100:1, 10 bar H₂, 40 °C, in MeOH). To bring the enantioselectivity to perfection an effective method for the isolation of the enantiopure carboxylic acid is suggested likewise.     

L-Proline-Catalyzed Knoevenagel Condensation: A Facile,Green Synthesis of (E)-Ethyl 2-Cyano-3-(1H-indol-3-yl)acrylates and (E)-3-(1H-Indol-3-yl)acrylonitriles

L-Proline has been utilized as a novel and ecofriendly catalyst in ethanol medium for the Knoevenagel condensation of indole-3-carboxyaldehydes and their N-methyl derivatives 1(a–e) and 4(a–e) with the active methylene compound, ethyl cyanoacetate (2) to afford substituted (E)-ethyl 2-cyano-3-(1H-indol-3-yl)acrylates 3(a–e) and 5(a–e) respectively. These products were reacted with dimethyl sulfate in the presence of PEG-600 as an efficient and green solvent to afford the corresponding N-mthylated derivatives 5(a–e). These Knoevenagel products react with 5% NaOH, yielding (E)-3-(1H-indol-3-yl)acrylonitriles 6(a–e) and 7(a–e).     

Efficient and practical asymmetric synthesis of isopropyl (R)-3-(3′,4′-dihydroxyphenyl)-2-hydroxypropanoate and its enantiomer

The highly enantioselective synthesis of (R)-isopropyl 3-(3′,4′-dihydroxyphenyl)-2-hydroxypropanoate and its enantiomer has been achieved starting from 3,4-dihydroxybenzaldehyde. The stereogenic centers were established through asymmetric dihydroxylation of (E)-isopropyl 3,4-bis(benzyloxy) cinnamate. A convenient manipulation in selective catalytic hydrogenation and deprotection was also accomplished in HCl-ⁱPrOH employing 10% Pd/C catalyst.     

Cu3/2PMo12O40改性骨架镍催化剂上羰基和碳-碳双键的加氢反应

 研究了Cu3／2PMo12O40表面改性的骨架镍催化剂上含羰基化合物（正丁醛、异丁醛、丙酮、丁酮和环己酮）及含碳－碳双键化合物（苯、糠醇和1－辛烯）的加氢反应．结果表明，随着骨架镍催化剂上Cu3／2PMo12O40附着量的增加，含羰基化合物的加氢反应速率上升，而含碳－碳双键化合物的加氢反应速率下降．与未改性的骨架镍催化剂相比，当骨架镍催化剂上Cu3／2PMo12O40附着量为6．3％时，羰基的加氢活性提高2倍以上，碳－碳双键的加氢活性下降30％以上．计算了各种化合物在催化剂上的表观活化能．结果表明，Cu3／2PMo12O40表面改性的骨架镍催化剂上，羰基加氢反应的表观活化能降低，而碳－碳双键加氢反应的表现活化能升高．从动力学角度讨论了Cu3／2PMo12O40对骨架镍催化剂的影响．用XPS对骨架镍表面的Cu3／2PMo12O40进行了研究，发现杂多酸盐的Keggin型结构已被破坏，Cu3／2PMo12O40分子中的Cu2＋被还原为Cu0，而Mo6＋被部分还原为Mo5＋和Mo4＋；Cu2＋和Mo6＋价态的变化是由骨架镍表面吸附的活泼氢所引起的．羰基加氢选择性的提高是Cu0和混合价态Mo共同作用的结果．     

Enantioselective hydrogenation of acetophenone by(1S,2S)-DPEN-Ru(Ⅱ)Cl_2(PPh_3)_2 encapsulated in Al-MCM-41

<正>A chiral ruthenium complex[(1S,2S)-DPEN]-RuCl_2(PPh_3)_2(DPEN = 1,2-diphenylethylenediamine,PPh_3 = triphenylphosphine) was encapsulated in the channel of Al-MCM-41 by electrostatic adsorption and 1,1-dichlorosilacyclobutane modification.The prepared heterogeneous catalyst showed the same catalytic activity and enantioselectivity as the corresponding homogeneous catalyst in the asymmetric hydrogenation of acetophenone,and could be reused at least seven times without significant loss of catalytic activity and enantioselectivity.     

Synthesis of optically active methyl 4-(4-biphenylyl)-3-hydroxybutanoate via enantioselective hydrogenation using a tartaric acid-modified nickel catalyst and recrystallization

Enantioselective hydrogenation of methyl 4-(4-biphenylyl)-3-oxobutanoate over a tartaric acid-modified Raney nickel catalyst gave the title compound in 82% ee, which was enantiomerically enriched by recrystallizations. The product was converted to an (R)-3-acetoxyglutaric acid half ester via a ruthenium-catalyzed oxidation.     

Mo(CO)3(NCMe)(PPh3)2: Synthesis, X-ray structure and evaluation of its catalytic activity for the homogeneous hydrogenation of olefins and their mixtures

The complex Mo(CO)₃(NCMe)(PPh₃)₂, was synthesized by the reaction of Mo(NCMe)₃(CO)₃ with two equivalents of PPh₃ and characterized by UV–Vis, IR, NMR and X-ray diffraction. This complex was used as a catalyst precursor for the hydrogenation of 1-hexene, styrene, cyclohexene and 2,3-dimethyl-1-butene and their mixtures under moderate conditions in homogeneous media. Under mild reaction conditions (T = 373 K, P = 60 atm), the substrates showed the following reactivity order: styrene > 1-hexene > cyclohexene > 2,3-dimethyl-1-butene. A quaternary equimolar mixture showed a different hydrogenation order: 1-hexene > cyclohexene > styrene > 2,3-dimethyl-1-butene; the presence of dibenzothiophene or mercury does not interfere with the activity of the catalyst.     

Selective hydrogenation of alkene in (3-trifluoromethyl) phenyldiazirine photophor with Wilkinson's catalyst for photoaffinity labeling

Selective hydrogenation of carbon-carbon double bond in the presence of nitrogen-nitrogen double bond in (3-trifluoromethyl) phenyldiazirine achieved with Wilkinson's catalyst.     

Selektive hydrierung von mesityloxid zu methylisobutylketon mit dem katalysator RhCl(PPh3)3

Mesityl oxide, dissolved in toluene is selectively hydrogenated to methylisobutylketone in the presence of the catalyst RhCl(PPh₃)₃. After 70% conversion the catalyst is deactivated. Without solvent, distilled but not degassed mesityl oxide is completely and selectively hydrogenated to methylisobutylketone. Turnover numbers are 4400. Under these hydrogenation conditions the catalyst is active for more than 100 hours.     

Electrochemical hydrogenation of 3-(methoxyphenyl)propenoic acids

Electrosynthesis can successfully be used for double bond hydrogenation in 3-(methoxyphenyl)propenoic acids. The corresponding 3-(methoxyphenyl)propanoic acids were produced in a virtually quantitative yield under the conditions of both electrocatalytic hydrogenation at the Ni cathode modified by electrodeposited dispersed nickel in a DMF-H₂O mixture in the presence of AcOH and direct electroreduction using mercury and glassycarbon cathodes in DMF with Bu₄NClO₄ as the supporting electrolyte, although the mechanisms of these processes are different.     

2-(4-氯苯基)-3-甲基丁酸的消旋

以酸酐及有机惰性溶剂作混合溶剂，少量叔胺等作催化剂，2-(4-氯苯基)-3-甲基丁酸能在比较温和的条件下基本完全消旋，收率接近90％。     

Behaviour of [PdH(dppe)2]X (X=CF3SO3-, SbF6-, BF4-) as proton or hydride donor: relevance to catalysis

The synthesis, characterization and properties of [PdH(dppe)(2)](+)CF(3)SO(3) (-).0.125 THF (1; dppe=1,2-bis(diphenylphosphanyl)ethane) and its SbF(6) (-) (1') and BF(4) (-) (1") analogues, the missing members of the [MH(dppe)(2)](+)X(-) (M=Ni, Pd, Pt) family, are described. The Pd hydrides are not stable in solution and can react as proton or hydride donors with formation of dihydrogen, [Pd(dppe)(2)](2+) and [Pd(dppe)(2)]. Complexes 1-1" react with carbocations and carbanions by transferring a hydride and a proton, respectively. Such H(-) or H(+) transfer occurs also towards unsaturated compounds, for example, hydrogenation of a C=C double bond. Accordingly, 1 can hydrogenate methyl acrylate to methyl propionate. Complex 1" is an effective (hourly turnover frequency=16) and very selective (100 %) catalyst for the hydrogenation of cyclohexen-2-one to cyclohexanone with dihydrogen under mild conditions. Density functional calculations coupled with a dielectric continuum model were carried out to compute the energetics of the hydride/proton transfer reactions, which were used to rationalize some of the experimental findings. Theory provides strong support for the thermodynamic and kinetic viability of a tetracoordinate Pd complex as an intermediate in the reactions.     

(1S,2S)-DPEN修饰的Ir/Al2O3催化苯乙酮及其衍生物的不对称加氢反应$

在碱性条件下制备了三氧化二铝负载的铱(Ir/γ-Al2O3)催化剂,并用于苯乙酮及其衍生物的不对称催化加氢反应.考察了不同的碱、碱浓度、手性二胺(1S,2S)-1,2-二苯基乙二胺[(1S,2S)-DPEN]浓度、反应温度和反应压力对催化剂及反应的影响.结果显示,在优化反应条件下,该催化剂表现出较高的催化活性和良好的对映选择性,其中异丁酰苯不对称催化加氢反应的对映选择性达到了80.3%.该催化剂不需要使用任何稳定剂,制备方法简单,催化性能稳定,通过简单的离心分离即可循环使用.     

Fabrication and Catalytic Properties of Films Based on Metal Ion-ligand Interaction between K_2PdCl_4 and 3-Amino-3-(4-pyridinyl)-propionitrile

This work presents a highly active and reusable heterogeneous film catalytic assembly for hydrogenation reduction of aromatic nitro compounds. The multilayer structures of PEI-(K2PdCl4-P1)n-film(PEI = polyethylenmine, P1 = 3-amino-3-(4-pyridinyl)-propionitrile) bound to quartz slides were fabricated by layer-by-layer(LbL) self-assembly method. Various characterization techniques including X-ray photoelectron spectroscopy(XPS), inductively coupled plasma OES spectrometer(ICP), UV-vis spectroscopy and atomic force microscopy(AFM) were employed to reveal the growth process of the resulting LbL multilayers in detail. Subsequent in situ reduction by H2 produced Pd nanoparticles embedded in such films were used as catalyst for the hydrogenation of nitroarenes. The catalytic performance test shows that the thin film catalyst can be applied to the hydrogenation reaction of various substituted nitroaromatics, and exhibits good catalytic activity and good catalyst stability. It is worth mentioning that our catalytic films can be easily removed from the reaction system in any time during the reaction, and the catalytic activity could be fully recovered when reused directly in another catalytic cycle for five times.     

丁二烯-b-甲基丙烯酸甲酯共聚物中C＝C的选择性催化加氢

以氯化三苯基膦铑为催化剂,对丁二烯-b-甲基丙烯酸甲酯共聚物的催化加氢反应进行了研究,用NMR、FTIR、动态粘弹谱和化学分析法对加氢产物进行了表征。证明RhCl[P(C₆H₅)₃]₃可有效地使共聚物中的C＝C加氢,且具有很高的选择性,未加氢的双键含量小于0.71%.