Functional monomers and polymers, 116. Asymmetric addition of n-butyllithium to aldehydes by chiral polymers and related compounds containing dimethylamino bornanol moieties

Asymmetric addition reaction of n-butyllithium to aldehydes was studied by using chiral polystyrene derivatives and chiral low molecular model compounds, both of which were derived from cis,endo-3-dimethylamino-2-hydroxybornane. The higher optical yields were achieved by using low molecular model compounds, and particularly the highest value was obtained in the case when ether was used as the solvent. The effect of reaction temperature, sort of the solvents and the molar ratio of the reagent to aldehyde on the asymmetric addition was also discussed.     

手性试剂(R)-β-甲基-γ-丁内酯及其衍生物的合成

以剑麻皂甙元为原料,经氧化降解得到了手性目标化合物.再与溴化氢/无水乙醇反应,以86%的收率得到(R)-4-溴-3-甲基丁酸乙酯;当目标化合物与苄溴/氢氧化钠反应时,可选择性地分别以91%和90%的收率得到(R)-4-苄氧基-3-甲基丁酸和(R)-4-苄氧基-3-甲基丁酸苄酯.合成产物的结构采用IR、~1HNMR和MS等确认.它们不仅为药物和生物活性天然化合物的合成提供了新的合成中间体,也为它们的新合成途径设计提供了机遇.     

Crosslinking of polystyrene by mono- and difunctional agents

Slightly crosslinked polystyrene networks are preferable to linear polystyrene in commercial uses where increased thermal properties are favoured. A novel method of production of macrocrosslinked networks has been developed by reaction of polystyrene with mono- and difunctional derivatives of p-xylene, durene and oligomeric chains (n<10) thereof. The reaction system consists of a common organic solvent such as acetic acid or butyl acetate and a catalyst such as H₂SO₄ or HClO₄; the reaction temperature varies between 60°C and 100°C. The degrees of crosslinking and thermal properties of the produced networks depend on the reaction system, the molar ratio of polymer to crosslinking agent and the reactivity of the functional groups; the gelation time varies between 3–12 hours for a fully crosslinked network. Promotion of the formation of regular structure networks without branches in the chains between crosslinks is achieved by the use of difunctional monomers, which favour the formation of linear polybenzylene chains between the polystyrene chains. Use of monofunctional monomers leads usually to branched and slightly crosslinked or grafted polystyrene. In both cases the regions of T_g and T_m increase up to 115°C and 350°C respectively as judged by DSC analysis. This novel crosslinking method has been also applied to crosslinking of copolymers of polystyrene and polymeric chains with aromatic structure in their backbone chain.     

A Highly Selective and Sensitive Chiral Derivatization Method for High- Performance Liquid Chromatographic Determination of the Stereoisomer Composition of Natural Products With Chiral Branched Alkyl Chains

In the study of chiral biologically active compounds such as pheromones, the analysis of the stereoisomer composition is essential to gain more insight into their stereochemical diversity, which affects the pheromone communication channels and therefore the diversification of species. This mini-review summarizes the development of fluorescence derivatization reagents for high-performance liquid chromatographic (HPLC) determination of the absolute configuration and stereoisomer composition of natural products with a chiral branched alkyl chain. The diastereomeric separation of anteiso fatty acids bearing a branched methyl group up to the C-26 position was achieved by reversed-phase HPLC under very low column temperature conditions using (1S,2S)-2-(2,3-anthracenedicarboximido)cyclohexanol as a derivatization reagent, enabling fluorescent detection of these compounds at femtomole levels. This method was also applicable to chiral alcohols and amines with chiral branched methyl groups using similar reagents containing a carboxyl group. These reagents were successfully applied to determine the absolute configurations and stereoisomer composition of the chiral alkyl chain of natural compounds including some insect pheromones, miyakosyne A, and plakoside A. The combination of these reagents and two-dimensional HPLC constitutes a very powerful tool for the analysis of the stereoisomers of natural crude samples. Furthermore, the analysis of some natural bioactive substances using this method demonstrated that natural substances are not always optically pure, consisting instead of stereoisomer mixtures exhibiting stronger activity than optically pure enantiomers. These results cast doubts on the concept of biological homochirality and demonstrate that natural pheromones do not always show the highest activity among all stereoisomers.

     

Practical Consequences of Non‐Linear Effects in Asymmetric Synthesis

The fundamental principles of non‐linear effects (NLE) are reviewed. Particular emphasis is placed on the case of asymmetric amplification, since it allows one to perform useful chemistry with a non‐enantiopure chiral auxiliary. A strong asymmetric depletion in a catalytic reaction may lead to an underestimation of the actual enantioselectivity of the fully resolved ligand. The study of NLE's is also proving useful as a mechanistic tool in asymmetric catalysis. Similar concepts may be extended to chiral reagents or to kinetic resolution. 1. What is a Non‐Linear Effect in Asymmetric Synthesis? 2. The Conditions for Observing a Non‐Linear Effect in Enantioselective Catalysis 3. Some Simple Models of NLE in Enantioselective Catalysis 4. Comparison of the Sizes of Asymmetric Amplifications 5. Rates and Non‐Linear Effects in Asymmetric Catalysis 6. Non‐Linear Effects Involving Chiral Reagents 7. Mechanistic Applications of Non‐Linear Effects 8. Synthetic Applications 9. Concluding Remarks     

Phosphoramidites: marvellous ligands in catalytic asymmetric conjugate addition

The development of an efficient catalytic system for enantioselective carbon-carbon bond formation by 1,4-addition of organometallic reagents (organolithium, Grignard, and organozinc reagents) to enones is a major challenge in organic synthesis. This Account presents the breakthrough realized in this field using chiral phosphoramidite ligands for copper-catalyzed dialkylzinc additions. Applications in catalytic routes to cycloalkanones as well as tandem and annulation procedures with excellent enantioselectivities are discussed.     

Advances in Immobilized Organocatalysts for the Heterogeneous Asymmetric Direct Aldol Reactions

The aim of this article is to collect the results published from the beginning (2000) on asymmetric direct aldol reactions taking place in the presence of immobilized chiral organocatalysts. The seven groups of organocatalysts discussed are: asymmetric direct aldol reactions catalyzed by: (1) covalently bonded immobilized hydroxyproline organocatalysts; (2) covalently bonded immobilized prolinamide organocatalysts; (3) covalently bonded immobilized peptide organocatalysts; (4) other covalently bonded immobilized chiral organocatalysts; (5) chiral organocatalysts bonded by ionic groups; (6) chiral organocatalysts with adsorptive bonding; and (7) other types of immobilized chiral organocatalysts. The main objective of this article based on results obtained by using about 360 immobilized organocatalysts, to bring to the focus of catalyst systems in which the aldol reactions yield beta-hydroxyketones of maximal optical purity, while keeping catalyst concentrations and reaction times as low and as short as possible. Trends recognized in data obtained in this field of investigation may mark out further tasks for the purpose of practical application.     

Chiral metallocycles: rational synthesis and novel applications

Chiralsupramolecular systems have attracted a great deal of interest from synthetic chemists over the past two decades because of their ability to mimic complex biological processes and their potential applications in enantioselective events such as asymmetric catalysis and chiral sensing. Chiral metallocycles, among the simplest forms of chiral supramolecular systems, are of particular interest because of their relative ease of synthesis. In this Account, we survey recent developments in the rational design and synthesis of chiral metallocyclic systems based on metal-ligand coordination and their potential applications in enantioselective recognition and catalysis. General design principles for metallocycles are first introduced with particular focus on thermodynamic and kinetic considerations. The symmetry requirements for the linear and angular building units, the influence of stoichiometries and reaction concentrations, and the roles of solvents are discussed. Optimum synthetic conditions for the self-assembly and directed-assembly of metallocycles are also compared. Three synthetic strategies for chiral metallocycles are broadly categorized based on the source of chirality, namely, (1) introduction of metallocorners containing chiral capping groups, (2) use of metal-based chirality owing to specific coordination arrangements, and (3) introduction of chiral bridging ligands. The bulk of this Account focuses on the third synthetic strategy with examples of chiral metallocycles built from atropisomeric bridging ligands based on the 1,1'-binaphthalene framework. The influences of ligand geometries and metallocorner configurations on the metallocycle structures are demonstrated. The synthetic utility of directed-assembly processes is illustrated with numerous examples of cyclic polygons ranging from nanoscopic dimers to a mesoscopic 47mer. Moreover, the directed-assembly processes offer exquisite control on structure, chirality, and functionality of the metallocycles. A number of interesting applications have been demonstrated with chiral metallocycles with diverse sizes and functionalities. For example, metallocycles with the Pt(diimine) metallocorners show interesting behaviors as luminophores in prototype light-emitting devices, chiral molecular squares based on 1,1'-binaphthyl-derived bipyridyl bridging ligands and fac-ReCO3Cl corners exhibit enantioselective luminescence in the presence of the 2-amino-1-propanol analyte, and chiral metallocycles based on 1,1'-binaphthyl-derived bialkynyl bridging ligands and cis-PtPEt2 corners activate Ti(IV) centers to catalyze highly enantioselective diethylzinc additions to aromatic aldehydes to afford chiral secondary alcohols. Additionally, chiral metallocycles synthesized via the weak-link approach (WLA) are shown to exhibit allosteric regulation. They experience significant changes in the cavity sizes and shapes upon the introduction of other ligands, with the resulting open structures serving as a catalyst for acyl transfer reaction or as an enantioselective recognition pocket. In summary, chiral metallocycles with much enhanced stability, favorable solubility characteristics, unprecedentedly large sizes, well-positioned functional groups, and desired chirality have been synthesized using a combination of self- and directed-assembly strategies. The applications of these chiral metallocycles in light-emitting devices, allosteric regulation, chiral sensing, and asymmetric catalysis have been demonstrated. The examples illustrated in this Account give testimony to chemists' ability, through chemical manipulations, to create large and complex chiral metallocycles that can potentially serve as mimics of natural enzyme systems.     

A comparison of the oxidizing ability of polystyrene‐supported linear and cyclic polyoxyethylene bound permanganates

The grafting of linear and cyclic polyoxyethylenes into DVB‐crosslinked chloromethylpolystyrene was carried out by treating with polyethyleneglycol (PEG₆₀₀). The complexations of crosslinked polystyrene‐supported linear and cyclic polyoxyethylene with permanganate functions were carried out. With this reagent, primary alcohols and secondry alcohols were converted to aldehydes and ketones and aldehyde to acid. The polymer acts as a reservoir of permanganate functions and releases them slowly as the substrates are being used up. The effect of solvent, molar excess of reagent, time, and temperature on oxidation behavior were investigated by choosing benzoin to benzil conversion as the model reaction. The linear polymeric reagent has greater reactivity than the cyclic polymer due to the greater availability of the reactive sites in the linear polymer than the cyclic polymer. Polymeric reagent could be used in excess to get a good yield without causing any separation problems and over oxidation products. The reagents have advantages of easy separation, regeneration and reuse. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1897–1905, 2005     

一种新型胺基树脂的制备

以乙酰化聚苯乙烯微球为原料经Mannich反应制备了一种新型胺基树脂,该树脂可替代氯甲基树脂制备的阴离子交换树脂及酶固定化胺基载体,因此,避免了氯甲基树脂生产中使用氯甲醚等致癌物质及多取代、二次交联等副反应的问题. 讨论了反应温度和时间、物料比、加料方式、介质中的水量等因素的影响. 最佳反应条件为无水乙醇介质,胺:醛:盐酸:乙酰基(摩尔比) 10:10:3.3:1,反应温度100℃,反应时间12 h,制备的胺基树脂氮含量为13.7 mmol/g. 机理研究显示乙酰基发生 多取代反应.     

树脂亲水性对水不溶性海因类杀菌剂杀菌活性的影响

在制成水不溶性海因类杀菌剂的基础上 ,在其载体树脂如氯球和醛基树脂上引入亲水基 ,如三甲胺基或三乙胺基。亲水基的引入可使氯球氧化为醛基树脂的反应温度降低 5～ 1 0℃ ,并使醛基的固载率提高 5%～ 1 0 %。水不溶性海因类杀菌剂亲水性的增加 ,使杀菌率从 86 9%提高到 97 1 %。     

表面接枝高密度磺酸基聚苯乙烯的制备及表征

以无水溴化铝为催化剂,对氯苯甲醛为醛基化试剂,通过傅克反应在聚苯乙烯微球表面接枝醛基;基于醛基的可氧化性,利用还原剂硝酸铵铈将树脂微球表面的醛基自由基化,引发对苯乙烯磺酸钠在树脂微球表面聚合,并对其进行表征。结果表明,聚苯乙烯微球磺酸化改性成功,优化的磺化工艺条件为:醛基含量1.5 mmol/g的聚苯乙烯微球用量0.3 g,对苯乙烯磺酸钠质量浓度40 g/L,硝酸铵铈质量浓度40 g/L,反应温度70℃,在此条件下制备的树脂表面磺酸基含量为58 mmol/g。     

Synthesis of Polymer‐Supported Fesulphos Ligands and their Application in Asymmetric Catalysis

The synthesis of two Fesulphos‐based chiral ligands and their immobilization on a polystyrene support is described. These supported chiral ligands act as very efficient catalysts in 1,3‐dipolar cycloaddition and allylic substitution reactions providing the products with excellent enantioselectivities (91 to >99 % ee). Filtration of the catalyst from the reaction mixtures allows simple product isolation. The polymer‐supported Cu complex of chiral ligand PS‐ 8 can be recycled without further addition of a copper salt in 1,3‐dipolar cycloaddition reactions.     

Design and applications of a solid-phase oxidizing reagent consisting of a crosslinked polystyrene matrix and a t-butyl hypochlorite function separated by a trimethylene spacer

A crosslinked polystyrene–supported solid-phase analogue of t-butyl hypochlorite containing a trimethylene spacer group between the polymer matrix and the t-butyl hypochlorite function was prepared and used as a recyclable oxidizing reagent for alcohols. The synthetic route to this new polymeric reagent involved a seven-step polymer-analogous reaction starting from styrene-divinyl benzene 2%-crosslinked polymer. A β-ketopropionic acid function was introduced into the polystyrene matrix by Friedel–Crafts reaction with succinic anhydride. The keto function in the resulting polymer (2) (capacity, 3.57 meq of COCH₂CH₂COOH/g) was converted to the methylene group by Clemmensen reduction using zinc amalgam and HCl. The carboxyl function in the product polymer (3) was converted to the acylmalonic ester function by malonic ester synthesis through the reaction of the polymeric acid chloride (4) with ethoxymagnesium diethylmalonate. The polymeric acyl malonic ester (5) was decarboxylated to yield the 2-oxopentyl polystyrene resin (6). This on Grignard reaction with methyl magnesium iodide followed by hydrolysis afforded the polystyrene derivative with the t-butyl alcohol function separated by three methylene groups (7) . The t-butyl alcohol resin (7) was converted to the corresponding hypochlorite resin (8) by reaction with sodium hypochlorite. The resin was found to have a capacity of 2.84 mmol Cl/g by iodometric analysis. The capacities of the resins 2–8 were determined from the weight changes in the corresponding conversions and verified by quantitative determination of the functional groups. This new hypochlorite was found to oxidize alcohols to carbonyl compounds in 85–98% yield. The oxidizing efficiency of this new reagent was found to be significantly greater than those of the reagents containing only one spacer and no spacer between the reagent function and the polymer support. The presence of a 3-methylene spacer also facilitated the hypochlorite formation step significantly.     

Synthesis and catalytic activity of optically active polymers containing oxime groups

Optically active polymers containing oxime groups have been prepared: (i) by partial quaternization of poly(4-vinyl pyridine) (P4VP) with phenacyloxime bromide and with (+)-(S)-1-bromo-2-methylbutane; and (ii) by reaction of the copolymer from 4VP and (+)-(S)-5-methyl-1-hepten-3-one with hydroxylamine. These polymers have been used as catalysts for the esterolysis of esters of p-nitrophenol with non-chiral and with chiral acids. The kinetic parameters of the catalytic process are markedly dependent on the structure of polymer and substrate. A moderate chiral discrimination of the antipodes of p-nitrophenyl 2-methylbutanoate is observed with the catalyst obtained from the copolymer of 4VP with (+)-(S)-5-methyl-1-hepten-3-one.     

2-吗啉醇盐酸盐的手性合成及晶体结构

以单一手性纯试剂与外消旋体化合物反应,合成了4对手性纯化合物(2R,3R,5S)-2-吗啉醇盐酸盐及其对映体(2S,3S,5R)-2-吗啉醇盐酸盐。其结构经IR、1HNMR、13CNMR及ESI-MS表征,利用X-射线单晶衍射法测定了其中一对对映体的空间构型。利用吗啉六元环椅式构象比船式构象稳定的特性,系统探讨了以构象稳定性促进目标化合物构型形成的手性化合物合成机制及规律,为手性化合物合成方法提供了新启示。     

手性CBS催化剂的研究进展

CBS催化剂是不对称还原反应中重要的手性催化剂,广泛应用于不对称合成领域中极重要的手性配体与手性中间体以及生物活性物质和天然物质的合成,具有巨大的市场潜力。CBS催化剂的制备通常是以(R/S)-脯氨酸为原料,先经某些反应保护氨基与羧基后进行格氏反应,之后脱去保护基团得前驱体(R/S)-α,α′-二苯基-2-吡咯烷甲醇,再与硼烷或其衍生物进行反应而得到。对CBS催化剂的制备方法、在有机合成中的应用、不对称催化反应的机理及其负载化进行了概述。     

Polymere Netzwerke als Träger

Historically ion exchangers are the oldest application of polymer networks as carriers. Electron exchange resins, polymerbound enzymes, Merrifield synthesis, polymeric reagents and immobilized microorganisms open nowadays a broad field of utilization. Of decisive importance for all these applications is the accessibility of these polymer fixed target groups. Gel permeation chromatography is a valuable tool to obtain information about swollen polymer networks and specially whether the pores are available from outside. The influence of reaction conditions on the structure of the network is described and the inherent problems are discussed with polymeric reagents as example.     

Chiral Aluminum Catalyst System for the Enantioselective Addition of Vinylaluminum Reagents to Aldehydes: Metal Controlled Reversal of Enantioselectivity

A chiral aluminum catalyst system has been developed for the enantioselective vinylation of aldehydes. β,β‐Disubstituted (E)‐vinylaluminum reagents, generated regio‐ and stereoselectively by the carboalumination of terminal alkynes with trimethylalumunim (Me₃Al), were used straightforwardly without transmetalation to vinyltitanium reagents in the subsequent enantioselective addition to aldehydes with a DPP‐H₈‐BINOL‐derived chiral aluminum catalyst at low catalyst loading (5 mol%). The reaction afforded the corresponding enantiomerically enriched secondary allylic alcohols with a reversal of the selectivity observed in closely related reactions catalyzed by a chiral titanium complex derived from the same ligand.

     

Homogeneous and heterogeneous sulfonation of polymers: A review

This paper reviews the various reactions used to sulfonate polymers, especially polystyrene. The mechanisms for the sulfonation of low molar mass compounds are also discussed. The commonly used sulfonation reagents are described, with an emphasis on SO₃ and its physical and chemical properties. Polymer sulfonations can be grouped into two general routes: one involving homogeneous sulfonation and the other heterogeneous reactions.