HDAC6选择性抑制剂WT161的合成工艺优化

本文报道了一条新的合成HDAC6选择性抑制剂WT161的路线。以辛二酸单甲酯为起始原料,经缩合、取代、还原、脱水共四步反应得到HDAC6选择性抑制剂WT161,总收率64.8%,目标产物结构均经过~1HNMR、~(13)CNMR和HRMS等确证。优化后的工艺路线原料成本低、反应条件温和、反应后处理更简单、产物收率更高,比较适合较大规模制备。     

生物基甘油氢解合成1,3-丙二醇催化剂的研究进展

1,3-丙二醇（1,3-PDO）作为聚酯单体原料有广阔的市场空间,在化妆品和医药等领域也被广泛应用.由生物基甘油选择氢解一步法合成1,3-PDO工艺被认为是一条绿色环保和高经济性的技术路线.我们在这里主要介绍了甘油氢解制备1,3-PDO催化剂的研究进展,对催化剂类型、催化剂的合成方法和工艺条件进行了归类总结;分析了多种催化剂体系的甘油氢解反应机理,指出了该反应工业化过程中存在的一些问题,并展望了今后的研究发展方向.     

D-脯氨酸催化的(3S,4S)-4-氨基-3-羟基-5-苯基戊酸衍生物的合成

报道了一条合成(3S,4S)-4-氨基-3-羟基-5-苯基戊酸(Ahppa)衍生物的新路线。以氨基保护的L-苯丙氨酸为起始原料,依次经Weinreb胺缩合、还原、aldol缩合及溴仿4步反应合成了3个Ahppa衍生物,总收率5.8%~6.7%,其结构经¹H NMR, ¹³C NMR和ESI-MS确证。对反应条件进行了探讨,结果表明：催化剂D-脯氨酸用量对反应收率影响不大,对立体选择性影响较大;氨基上保护基体积较大有利于提高反应立体选择性。     

Gabriel合成胺反应的工艺改进

采用经典的Gabriel反应合成了直链型多胺骨架,并用1H/13C NMR,MS等方法确证了中间体以及目标化合物的结构.研究表明,在实验条件下,Gabriel反应经历了新的反应历程;经过工艺改进,建立了一条效率较高的工艺路线.     

NMDA受体2A选择性抑制剂NVP-AAM077 的高效合成

本文报道一条以2,3-二氨基甲苯为原料，经过8步反应合成NMDA受体2A选择性抑制剂NVP-AAM077的高效率路线，其总收率为54%。合成中使用的关键反应包括NaIO₄/DMF介导的氧化芳苄溴到芳醛的反应以及亚膦酸酯对亚胺的加成反应等。     

催化还原胺类衍生物N-单烷基化反应一锅法合成4,6-二(异丙基氨基)-1,3-苯二酚

以 2-氯-4,6-二硝基-1,3-苯二酚为原料,丙酮为烷基源,氢气为还原剂,研究了在10%Pd/C催化剂上一锅法合成N-单烷基氨基苯酚化合物 4,6-二(异丙基氨基)-1,3-苯二酚的反应工艺. 考察了反应条件如醋酸量、丙酮浓度、氢气压力、催化剂量和反应时间对反应的影响,开发出一条高收率、高选择性制备N-单烷基氨基苯酚化合物的合成路线.     

(2S,3aR,7aS)-八氢-1H-吲哚-2-甲酸苄酯的合成

通过合成路线的改进以及合成工艺的优化,方便高效地得到了抗高血压药物群多普利的关键中间体(2S,3aR,7aS)-八氢-1H-吲哚-2-甲酸苄酯.产品结构及绝对构型通过NMR及HPLC进行表征,与文献报道的数据完全一致.最终以99%的对映选择性及13.2%的产率得到目标化合物.为群多普利关键中间体的合成提供了一条可工业化的途径.     

催化还原胺类衍生物N．单烷基化反应-锅法合成4，6-二（异丙基氨基）-1，3-苯二酚

以2-氯-4,6-二硝基-1,3-苯二酚为原料,丙酮为烷基源,氢气为还原剂,研究了在10％Pd／C催化剂上-锅法合成N-单烷基氨基苯酚化合物4,6-二（异丙基氨基）-1,3-苯二酚的反应工艺．考察了反应条件如醋酸量、丙酮浓度、氢气压力、催化剂量和反应时间对反应的影响,开发出-条高收率、高选择性制备N-单烷基氨基苯酚化合物的合成路线．     

2，3，6，3′，4′-五氧乙酰基蔗糖的合成与表征

以蔗糖为原料通过羟基的选择性保护、脱保护及迁移合成了三氯蔗糖的中间体2,3，6，3’，4’-五氧乙酰基蔗糖（6-PAS）。在蔗糖羟基的选择性保护反应中采用4．二甲氨基吡啶（DMAP）为催化剂，有效地提高了产率．并利用HPLC对选择性脱保护和乙酰基迁移2步反应进行跟踪，确定了较优的合成路线。并用核磁共振和红外光谱对产品进行表征。羟基选择性保护最佳反应条件为：使用质量分数为10％的催化剂，三苯甲基化反应在50℃进行4h，乙酰化反应在105℃进行3h。在该条件下进行反应，产率为81．9％。     

(S)-6-苄氧基-5-羟基-3-氧代-己酸叔丁酯合成新方法

研究了一条新的路线用于(S)-6-苄氧基-5-羟基-3-氧代-己酸叔丁酯的合成. 以廉价、易得的R-环氧氯丙烷为起始原料, 经过几步比较温和的反应得到目标化合物. 在此基础上, 通过对催化剂三氟化硼乙醚用量的考察以及两条反应路线优缺点的比较, 找到了一条适合大规模制备的工艺路线. 该路线具有收率高、原料易得、反应条件温和、产物容易分离、提纯等特点.     

Direct Arylation in the Presence of Palladium Pincer Complexes

Direct arylation is an atom-economical alternative to more established procedures such as Stille, Suzuki or Negishi arylation reactions. In comparison with other palladium sources and ligands, the use of palladium pincer complexes as catalysts or pre-catalysts for direct arylation has resulted in improved efficiency, higher reaction yields, and advantageous reaction conditions. In addition to a revision of the literature concerning intra- and intermolecular direct arylation reactions performed in the presence of palladium pincer complexes, the role of these remarkably active catalysts will also be discussed.     

Hydrogenation Catalysts Based on Polynuclear Palladium Complexes with Organophosphorus Ligands

A new procedure is proposed for the preparation of hydrogenation catalysts. This procedure includes the synthesis of cyclic tetranuclear palladium complexes with bridging diphenylphosphide ligands followed by a reaction with Pd(CH₃COO)₂ in the presence of hydrogen to form nanosized particles. In the test catalysts, the ensembles of palladium atoms (or palladium hydrides) immobilized on supramolecular structures formed by the association of phosphinidene and phosphide complexes of palladium are responsible for the catalytic activity.     

Synthesis and catalytic application of Pd complex catalysts: Atom‐efficient cross‐coupling of triarylbismuthines with haloarenes and acid chlorides under mild conditions

Palladium‐catalysed cross‐coupling reactions are some of the most frequently used synthetic tools for the construction of new carbon–carbon bonds in organic synthesis. In the work presented, Pd(II) complex catalysts were synthesized from palladium chloride and nitrogen donor ligands as the precursors. Infrared and ¹H NMR spectroscopic analyses showed that the palladium complexes were formed in the bidentate mode to the palladium centre. The resultant Pd(II) complexes were tested as catalysts for the coupling of organobismuth(III) compounds with aryl and acid halides leading to excellent yields with high turnover frequency values. The catalysts were stable under the reaction conditions and no degradation was noticed even at 150°C for one of the catalysts. The reaction proceeds via an aryl palladium complex formed by transmetallation reaction between catalyst and Ar₃Bi. The whole synthetic transformation has high atom economy as all three aryl groups attached to bismuth are efficiently transferred to the electrophilic partner.     

Palladium-triazine aminoalcohol nanocomposite, its reactivity on Heck reaction

Several studies on dendrimer synthesis and reactivity have been carried out in order to control the size and functionality of compounds. From such studies, it has been suggested that these molecules may be used as ligands to synthesize potential homogeneous catalysts, firstly, in order to get the benefits of both homo- and heterogeneous catalysis (i.e. high activity and/or selectivity, good reproducibility, accessibility of the metal site, intermediaries detection, etc.); secondly, because, unlike other polymeric species, they can be readily recoverable after reaction. In this paper, following our interest in homogeneous catalysts, we would like to present our findings from studies on the synthesis and characterization of a prime molecule, triazine aminoalcohol, as starting or zero generation dendrimer and its interaction-reaction with palladium nanoparticles as well as our results on the reactivity on Heck type catalysis.     

Heck reactions of iodobenzene and methyl acrylate with conventional supported palladium catalysts in the presence of organic and/or inorganic bases without ligands

The vinylation of iodobenzene with methyl acrylate has been studied with several supported palladium catalysts in N-methylpyrrolidone in the presence of triethylamine and/or sodium carbonate. The reaction can be performed in air without any solubilizing or activating ligands. It was found that significant amounts of palladium leach out into the solvent and these dissolved Pd species essentially catalyze the reaction. It is interesting, however, that almost all the palladium species in the solution can redeposit onto the surface of the supports after the reaction has been completed (at 100% conversion of iodobenzene). Thus, the catalysts were recyclable without loss of activity. The use of both inorganic and organic bases is very effective in the promotion of the palladium redeposition as well as in the enhancement of the reaction rate. For Heck reactions with bromobenzene and chlorobenzene it was found that the use of triethylamine and sodium carbonate increases the selectivity of the Heck coupling product (benzene is also produced for these two substrates), but the mixed bases do not affect the overall rate of reaction as much.     

Alternating copolymerization of carbon monoxide and vinyl arenes using [N,N] bidentate palladium catalysts

The alternating copolymers of carbon monoxide (CO) and vinyl arene monomers, namely aromatic polyketones, are a family of attractive engineering plastic. In the catalytic synthesis of this kind of polymeric materials, [N,N] bidentate palladium catalysts represent the most successful catalytic systems. In this review, we introduce the present status of polyketone synthesis, with a focus on the aromatic polyketones made from vinyl arene and CO. We also address the palladium-catalyzed CO/vinyl arene alternating copolymerization mechanism. A variety of [N,N] bidentate palladium catalysts bearing 2,2′-bipyridine, 1,10-phenanthroline, α-diimine, and pyridine-imine ligands are surveyed for CO/vinyl arene copolymerization. The effects of vinyl arene monomer, counteranion, and solvent on copolymerization are also discussed. The copolymerization stereochemistry including chain end-control and enantiomorphic site control mechanisms is introduced. This review aims to promote the design of [N,N] bidentate palladium catalysts for CO/vinyl arene copolymerization for the development of high-performance aromatic polyketones.     

Reaction of vinyl epoxides with palladium-switchable bisnucleophiles: synthesis of carbocycles

The selective activation of substrates I, potential bisnucleophiles, was achieved by using different palladium catalysts. The synthetic potential of this strategy has been demonstrated in the regiodivergent synthesis of carbocycles from substrates of type I, bearing malonate-type pronucleophiles and an alkenyl stannane, with vinyl epoxides. A selective palladium-catalyzed reaction of I with the vinyl epoxide gives rise to an allylic alcohol, which, after activation as a carbonate, led to the cyclization product by a second palladium-catalyzed reaction. The transmetalation process is favored with palladium-catalysts without phosphines or arsines as the ligands. On the other hand, the use of palladium complexes with PPh3 as the ligand inhibits the transmetalation pathway and promotes the nucleophilic attack of the malonate-type anions on the intermediate (eta 3-allyl)-palladium complexes.     

新一代高活性后过渡金属烯烃聚合催化剂

介绍了近几年发展起来的新一代后期过渡金属(Fe,Co,Ni,Pd)烯烃聚合催化剂,对催化剂的结构、性能及催化烯烃聚合进行了阐述。     

Functionalized isoxazole and isothiazole ligands: design,synthesis, palladium complexes,homogeneous and heterogeneous catalysis in aqueous media

Homogenous and heterogeneous palladium catalysts with functionalized izoxazole and isothiazole ligands were developed for the cross-coupling reactions. The catalysts possessed high activity and were suitable for the repeated use. Compared with commonly used organic solutions, application of water and its mixtures with methanol as a reaction medium significantly intensifies catalysis with no side being formed. The obtained results are promising for the development of effective and ecologically friendly technologies of synthesis of important compounds such as polyfunctional biaryls, arylated olefins, acetylenes and their heterocyclic analogs.     

Palladium- and copper-catalyzed synthesis of medium- and large-sized ring-fused dihydroazaphenanthrenes and 1,4-benzodiazepine-2,5-diones. control of reaction pathway by metal-switching

Methods for the synthesis of dihydroazaphenanthrene fused to macrocycles (2) and medium-ring heterocycles (4), as well as 1,4-benzodiazepine-2,5-diones (5), are developed. A distinctly different catalytic property of palladium and copper catalysts was uncovered that leads to the development of a divergent synthesis of two different heterocyclic scaffolds from the same starting materials, simply by metal-switching. Thus, starting from linear amide 3, palladium acetate triggers a domino intramolecular N-arylation/C-H activation/aryl-aryl bond-forming process to provide 4, while copper iodide promotes only the intramolecular N-arylation reaction leading to 5. In combination with the Ugi multicomponent reaction (Ugi-4CR) for the preparation of the linear amides, a two-step synthesis of either the 5,6-dihydro-8H-5,7a-diazacyclohepta[jk]phenanthrene-4,7-dione (4) or 1,4-benzodiazepine-2,5-diones (5), by appropriate choice of metal catalyst, is subsequently developed from very simple starting materials.