R-沙美特罗的合成方法

近年来手性沙美特罗的合成方法有微生物催化、不对称氢化、CBS(Corey-Bakshi-Shibata)还原反应及不对称Henry反应、手性(Salen)Co试剂催化的HKR(末端环氧不对称水解动力学)拆分反应等。对这些方法进行比较,结果表明,不对称催化合成由于其反应收率高、反应产物光学纯度高、操作容易控制,在目前手性药物的合成中处于主导地位。此外酶催化不对称合成、手性辅基诱导的对映选择性合成等方法也是有效的途径。     

醛和胺原位生成的手性亚胺盐催化的不对称环氧化

光学纯的环氧化物是合成许多药物和天然产物的重要中间体并构成不对称碳碳键的重要合成子 ,因此寻找不对称环氧化反应体系总是有机化学研究的重点和热点[1～ 3 ] .从 Sharpless[4 ] 到 Jacobsen[5] 的手性金属配合物催化体系 ,到杨丹 [6] 和施以安[7] 的手性有机酮催化体系 ,都取得了突破性的进展 ,并在天然产物、药物合成中得到了应用 [1,2 ,8] .但这些体系都有其局限性 ,每一类体系只能适用于某一类烯烃 ,因此开拓适用性更广的不对称环氧化催化剂 ,仍然是对有机化学工作者的挑战 .近年来 ,一种新的体系 ,即用手性亚胺盐或者手性亚胺盐氧…     

水解动力学拆分3-(1-萘氧基)-1,2-环氧丙烷

研究了3-(1-萘氧基)-1,2-环氧丙烷[(R,S)-1]在Salen Co(Ⅲ)催化下的水解动力学拆分(HKR)。以转化率和ee值为指标,考察了催化剂用量、底物用量、反应温度、反应时间、溶剂种类等对HKR反应的影响。最佳HKR条件为:(R,S)-1 10 mmol,w[Salen Co(Ⅲ)]=0.75%,THF 1 mL,水0.5 eq,于25℃水解40 h,(R,S)-1的转化率为49.5%,(S)-1的ee为99.5%。     

催化的外消旋环氧化合物不对称开环

用较易得到的(R,R)-1,2-二苯基乙二胺(DPEDA)与2-羟基-5-甲基-3-叔丁基苯甲醛缩合,得到手性Salen,再与Co络合,氧化后得到Salen型手性催化剂(R,R)-2.(R,R)-2可催化外消旋环氧化物的动力学水解拆分,所得手性二醇和手性环氧化合物对映体过量最高分别可达99%和92%.     

Co(Ⅲ)(Salen)催化的外消旋环氧化合物不对称开环

用较易得到的(R,R)-1,2-二苯基乙二胺(DPEDA)与-2-羟基-5-甲基-3-叔丁基苯甲醛缩合,得到手性Salen,再与Co络合,氧化后得到Salen型手性催化剂(R,R)-2。(R,R)-2可催化外消旋环氧化物的动力学水解拆分,所得手性二醇和手性环氧化合物对映体过量最高分别可达99%和92%。     

手性Salen-Co(Ⅱ)配合物催化芳香酮不对称还原反应研究

目前 ,以廉价的氢气为氢源 ,由潜手性的酮不对称加氢是制备手性醇最好的方法之一 [1] .但存在手性催化剂的膦配体不稳定以及贵金属 ( Ru、Rh)的流失等问题 .硼氢化钠是一种较温和的氢化试剂 ,Mukaiyama等用具有 C2 对称轴的一系列光学活性的二亚胺钴配合物催化硼氢化钠不对称还原芳香酮 ,实现了以硼氢化钠为氢源的不对称氢化反应 [2 ] .手性 Salen是一种用途广泛的配体 ,已用在不对称催化环氧化 [3 ]、环丙烷化 [4]、杂 Diels- Alder反应 [5]及环氧化合物的水解动力学拆分 [6]、仲醇动力学拆分[7] 等反应中 ,并显示出很好的不对称诱导效…     

叔醇的动力学拆分研究进展

手性叔醇结构广泛存在于生物活性物质、天然产物和药物分子中,实现其高效不对称催化合成具有重要意义.消旋醇的动力学拆分是一种合成高光学纯度手性醇的重要方法,然而由于叔醇α-碳上带三个不同的非氢取代基团,手性识别难度较大,因而发展高效且具有广泛底物适用性的叔醇动力学拆分方法具有较大的挑战.尽管如此,近年来非酶催化的叔醇的动力学拆分领域取得了快速的发展,一些新颖的不对称催化反应、催化体系被成功应用于叔醇的动力学拆分反应中.对叔醇动力学拆分反应进行了系统总结,分类介绍了这些反应的底物适用性、特点、机理以及局限等,并对该领域的未来发展进行展望.     

表面上和纳米孔道内以及乳液中的手性催化

多相手性催化是合成手性化合物的有效途径之一,开发高活性、高选择性的多相手性催化剂并应用于不对称催化反应是兼具基础科学和应用科学背景的重要研究方向. 本文综述了近年来具有代表性的固体表面上、纳米孔道内以及手性乳液体系中的多相手性催化研究进展,着重对本实验室近年来在该领域中的探索研究进行了介绍,涉及的重要手性催化反应包括氢化、氢转移、氢甲酰化、环氧化、环氧化物水解动力学拆分、Aldol反应和Diels-Alder反应等. 我们的研究表明,手性修饰纳米粒子催化剂上的手性氢化反应可以获得95% ee以上的手性选择性以及高达 20 000 h-1 的TOF, 手性氢甲酰化反应得到90% ee的手性选择性;在手性催化剂组装的乳液体系中,催化不对称Aldol反应获得高达99% ee的手性选择性,催化活性得到显著提升,乳液氢转移反应的TOF可达3×105 h-1;在纳米孔中多个手性环氧化反应的例子显示出孔道效应能够显著提高手性选择性,并发现在纳米反应器中的环氧化物水解动力学拆分反应显示出催化剂协同活化效应,使催化反应的活性大幅度提高. 本文还讨论了表面、界面上以及孔道中的催化剂组装、孔道限阈以及多中心协同效应等因素对多相手性催化反应性能的影响.     

《化学通报》网络版(Chemistry Online)2005年第7期论文摘要

[w074]环氧化合物的不对称开环反应AsymmetricRingOpeningofEpoxides王朝阳(西南交通大学药学院四川峨眉614202)介绍了在不同手性配体和路易斯酸的催化下内消旋环氧化合物的不对称开环反应与外消旋末端环氧化合物的水解动力学拆分与开环反应;并指出了环氧化合物的这两种反应在不对称合成与手性药物领域的应用价值以及在工业上广阔的应用前景。Progressesinasymmetricringopening(ARO)ofmesoepoxideswithdifferentchiralligand,andthehydrolytickinetic resolution(HKR)ofracemicterminalepoxidescatalyzedbychiralSalenmetalcomplexwer…     

α,β-不饱和羰基化合物的不对称Diels-Alder反应研究进展

Diels-Alder反应是典型的[4+2]环合反应,自被发现以来备受化学家们的重视.不对称Diels-Alder反应是合成手性中间体的有效手段,在手性药物和天然产物全合成中得到广泛应用.α,β-不饱和羰基化合物是有机合成反应的关键中间体,根据其结构特点和催化体系类型,分类阐述了α,β-不饱和羰基化合物为亲双烯体的不对称正电子需求Diels-Alder反应的研究进展.     

Commercialization of the hydrolytic kinetic resolution of racemic epoxides: toward the economical large-scale production of enantiopure epichlorohydrin

The hydrolytic kinetic resolution of racemic terminal epoxides utilizing chiral (salen)Co(III) catalysts provides practical access to enantiopure epoxides and diols. However, general issues surrounding catalyst activation combined with the specific problem of racemization of epichlorohydrin served to make the large-scale production of (R)- or (S)-epichlorohydrin difficult and uneconomical. A process for the large-scale production and isolation of active (salen)Co(III)OAc catalyst and a method of catalyst reduction after reaction using ascorbic acid have been developed to overcome these issues.     

烯丙基缩水甘油醚的合成

烯丙醇和环氧氯丙烷在三氟化硼乙醚络合物的催化作用下进行加成和环化反应制得标题化合物。研究了催化剂用量、反应原料配比及碱用量对产物收率的影响。     

多乙酰氧基硅烷与环氧氯丙烷的开环反应

本文详细地研究了在5-叔丁基呋喃甲酸铬的存在下,多乙酰氧基硅烷与环氧氯丙烷的开环反应及其产物。     

乙二醇二缩水甘油醚的合成及作为阳离子型紫外光固化稀释剂性能研究

以三氟化硼乙醚络合物为催化剂,以氢氧化钠为成环反应的闭环剂,利用乙二醇和环氧氯丙烷为原料合成了乙二醇二缩水甘油醚.研究了催化剂三氟化硼乙醚络合物用量、环氧氯丙烷和乙二醇摩尔比、氢氧化钠和乙二醇摩尔比,以及成环反应温度这些因素对合成反应的影响.结果表明较好的合成反应条件是:三氟化硼乙醚络合物质量分数为0.40%,环氧氯丙烷和乙二醇较佳摩尔比为2.4:1,氢氧化钠和乙二醇较佳摩尔比为2.2:1,较佳的成环反应温度为30℃.同时,把乙二醇二缩水甘油醚作为稀释剂加入到环氧树脂E-51中,利用三芳基锍鎓六氟锑酸盐作为引发剂,制备了阳离子型紫外光固化涂料,其紫外光固化膜的拉伸强度为46.25MPa,杨氏模量为1487.26MPa,断裂伸长率为6.27%.     

Kinetic studies for the esterification of acetic acid with epichlorohydrin over an anion exchange resin catalyst

The kinetics of the esterification reaction between acetic acid and epichlorohydrin catalysed by Purolite A-520E strong basic anion exchange resin was studied. The effects of certain parameters such as stirring speed, particle diameter, temperature, catalyst amount and molar ratio between reactants were experimentally determined. It was found that the overall reaction rate is intrinsically kinetically controlled. The partial orders of reaction with respect to catalyst, acetic acid and epichlorohydrin were determined. A reaction mechanism is proposed. Based on chromatographic data and taking into account the partial orders of reaction, a more detailed kinetic model is suggested.      

Enhanced cooperativity through design: pendant Co(III)--salen polymer brush catalysts for the hydrolytic kinetic resolution of epichlorohydrin (salen=N,N'-bis(salicylidene)ethylenediamine dianion)

The Co(III)--salen-catalyzed (salen=N,N'-bis(salicylidene)ethylenediamine dianion) hydrolytic kinetic resolution (HKR) of racemic epoxides has emerged as a highly attractive and efficient method of synthesizing chiral C(3) building blocks for intermediates in larger, more complex molecules. HKR reaction rates have displayed a second order dependency on the concentration of active sites, and thus researchers have proposed a bimetallic transition state for the HKR mechanism. Here we report the utilization of pendant Co(III)--salen catalysts on silica supported polymer brushes as a catalyst for the HKR of epichlorohydrin. The novel polymer brush architecture provided a unique framework for promoting site-site interactions as required in the proposed bimetallic transition state of the HKR mechanism. Furthermore, the polymer brushes mimic the environment of soluble polymer-based catalysts, whereas the silica support permitted facile recovery and reuse of the catalyst. The polymer brush catalyst displayed increased activities over the soluble Jacobsen Co--salen catalyst and was observed to retain its high enantioselectivities (>99 %) after each of five reactions despite decreasing activities. Analysis indicated decomposition of the salen ligand as an underlying cause of catalyst deactivation.     

Synthesis of optically active 2-hydroxy monoesters via-kinetic resolution and asymmetric cyclization catalyzed by heterometallic chiral (salen) Co complex

The binuclear chiral (salen) Co complexes bearing Lewis acids of Al and Ga catalyze regio- and enantioselective ring opening of terminal epoxides with carboxylic acids. The ring opened product of epichlorohydrin with carboxylic acids followed by cyclization step in the presence of catalyst and base represent straightforward, efficient methods for the synthesis of enatiomerically enriched (>99% ee) valuable terminal epoxides. Strong synergistic effects of different Lewis acid of Co-Al and Co-Ga were exhibited in the catalytic process.     

Study of the O-glycidylation of natural phenolic compounds. The relationship between the phenolic structure and the reaction mechanism

The O-alkylation reaction by epichlorohydrin of some natural phenolic compounds such as 4-methylcatechol, gallic acid, protocatechuic acid, pyrogallol and resorcinol was investigated. Phenolic compounds reacted first with epichlorohydrin in the presence of benzyltriethylammonium chloride as phase transfer catalyst. Then, an aqueous solution of sodium hydroxide was added.It was demonstrated that the two competitive mechanisms involved in the O-alkylation reaction were highly dependent of the starting material. The O-alkylated products obtained in this reaction could be further used as bisphenol A substitutes in the synthesis of epoxy resins pre-polymers.     

Synthesis of Novel Polyether Polyol by Using Double Metal Cyanide

Hydroxyl-terminated novel polyether polyols were synthesized by polymerization of epichlorohydrin (ECH) catalyzed by double metal cyanide (DMC) catalyst. The effects of reaction temperature and catalyst concentration on the polymerization of Polyether Polyol were studied. The molecular structure and the damping properties were measured by IR spectra, ¹H-NMR spectra and the dynamic mechanical analysis.     

An environmentally benign route for epichlorohydrin from allyl chloride epoxidation catalyzed by heteropolyphosphatotungstate

In the absence of organic solvent, allyl chloride was epoxidized with aqueous hydrogen peroxide catalyzed by a heteropolyphosphatotungstate catalyst with very good activity and recycling activity. Under optimized conditions, an epichlorohydrin yield of 88.7% was achieved in the first run; after two recycles, the epichlorohydrin yield remained still above 85.0%. Various factors affecting the catalytic reaction were investigated systematically. The reaction rate of hydrogen peroxide in the epoxidation of allyl chloride is zero order with respect to hydrogen peroxide. The activation energy is 52.27 kJ/mol.