The Role of Secondary Interactions in the Asymmetric Palladium‐Catalysed Hydrosilylation of Olefins with Monophosphane Ligands

A structure‐activity survey of monophosphane ligands used in the asymmetric palladium‐catalysed hydrosilylation reaction of olefins is presented and used to assess the role of secondary interactions on catalyst activity and selectivity.     

Asymmetric Homogeneous Hydrogenation in Flow using a Tube‐in‐Tube Reactor

In this update, the asymmetric homogeneous hydrogenation of a number of trisubstituted olefins utilizing the recently developed tube‐in‐tube gas‐liquid flow reactor is described. A number of chiral iridium‐ and rhodium‐based catalysts and other parameters such as pressure, solvent, temperature and catalyst loading were screened. The advantage of the flow set‐up for rapid screening and optimization of reaction parameters is illustrated. Furthermore, a comparative study using batch conditions aided in the optimization of the flow reaction set‐up. The set‐up was further modified to recycle the catalyst which prolonged catalytic activity.     

高通量筛选技术在多相催化研究中的应用

通过对组合催化研究的关键因素－－催化剂高通量筛选技术的评价分析认为：在对已有的催化体系和催化剂优化的同时，如何高校研制开发新筛选检测技术，诸如反应器设计和检测器的选择，是组合催化研究的主导思想，对此的深刻理解和运用将增强实验室的创新能力。     

Highly Modular P‐O‐P Ligands for Asymmetric Hydrogenation

The preparation of a library of new P‐O‐P ligands (phosphine‐phosphites and phosphine‐phosphinites), easily available in two synthetic steps from enantiopure Sharpless epoxy ethers, is reported. The “lead” catalyst of the series has proven to have outstanding catalytic properties in the rhodium‐catalysed asymmetric hydrogenation of a wide variety of functionalised alkenes (16 examples). The excellent performance and modular design of the catalysts makes them attractive for future applications.     

Highly Selective Cobalt‐Catalyzed Hydrovinylation of Styrene

Phosphine complexes of cobalt halide salts activated by diethylaluminum chloride are shown to yield highly active catalysts in the hydrovinylation of styrene, with unprecedented high selectivity to the desired product 3‐phenyl‐1‐butene (3P1B). Double‐bond isomerization, a common problem in codimerization reactions, only occurs after full conversion with these catalyst systems, even at elevated temperature. The most active catalysts are based on cobalt halide species combined with either C₁‐ or C₂‐bridged diphosphines, heterodonor P,N or P,O ligands, flexible bidentate phosphine ligands or monodentate phosphine ligands. Kinetic investigations show an order >1 in catalyst, which indicates either the involvement of dinuclear species in the catalytic cycle or partial catalyst decomposition via a bimolecular pathway.     

Modular P?OP Ligands in Rhodium‐Mediated Asymmetric Hydrogenation: A Comparative Catalysis Study

Highly efficient and enantioselective hydrogenation reactions for α‐(acylamino)acrylates, itaconic acid derivatives and analogues, α‐substituted enol ester derivatives, and α‐arylenamides (25 substrates) catalyzed by chiral cationic rhodium complexes of a set of P OP ligands have been developed. The catalytic systems derived from these P OP ligands provided a straightforward access to enantiomerically enriched α‐amino acid, carboxylic acid, amine, and alcohol derivatives that are valuable chiral building blocks. Excellent efficiencies (full conversion in all cases) and extremely high enantiomeric excesses (94–99% ee) were achieved for a wide range of α‐substituted enol ester derivatives, regardless of the substitution pattern. The R‐oxy group of the ligand (methoxy or triphenylmethoxy) strongly influences the enantioselectivity and catalytic activity. Greater steric bulk around the metal centre correlated to greater (or similar) enantioselectivity, but also to slower hydrogenation. Furthermore, the hydrogenation rates observed with the four model substrates follow the same trend, independently of the R‐oxy group of the ligand: methyl 2‐acetamidoacrylate>dimethyl itaconate>1‐phenylvinyl acetate>N‐(1‐phenylvinyl)acetamide. A substrate‐to‐catalyst ratio (S/C) of up to 10,000:1 was sufficient for total hydrogenation of a model substrate of intermediate reactivity (dimethyl itaconate), and did not imply any loss in conversion or enantioselectivity.     

Dendronized Poly(Ru‐BINAP) Complexes: Highly Effective and Easily Recyclable Catalysts For Asymmetric Hydrogenation

A new kind of dendronized polymeric chiral BINAP ligands has been synthesized and applied to the Ru‐catalyzed asymmetric hydrogenation of simple aryl ketones and 2‐arylacrylic acids. These dendronized poly(Ru‐BINAP) catalysts exhibited high catalytic activity and enantioselectivity, very similar to those obtained with the corresponding parent Ru(BINAP) and the Ru(BINAP)‐cored dendrimers. It was found that the pendant dendrons had a major impact on the solubility and the catalytic properties of the polymeric ligands. These polymeric catalysts could be easily recovered from the reaction solution by using solvent precipitation, and the reused catalyst showed no loss of activity or enantioselectivity.     

The Development of Enantioselective Rhodium‐Catalysed Hydroboration of Olefins

Rhodium‐catalysed enantioselective hydroboration of olefins is a valuable synthetic transformation, typically employing a chiral catalyst and an achiral borane source. The pertinent chemo‐, regio‐ and enantioselectivity issues of this reaction are discussed. However, the main emphasis of this review is on the evolution of catalytic asymmetric hydroboration. This has primarily relied upon the development and application of chiral bidentate P,P and P,N ligands which have exhibited varying degrees of success in this transformation.     

Virtual Combinatorial Chemistry and Pharmacological Screening: A Short Guide to Drug Design

Traditionally, drug development involved the individual synthesis and biological evaluation of hundreds to thousands of compounds with the intention of highlighting their biological activity, selectivity, and bioavailability, as well as their low toxicity. On average, this process of new drug development involved, in addition to high economic costs, a period of several years before hopefully finding a drug with suitable characteristics to drive its commercialization. Therefore, the chemical synthesis of new compounds became the limiting step in the process of searching for or optimizing leads for new drug development. This need for large chemical libraries led to the birth of high-throughput synthesis methods and combinatorial chemistry. Virtual combinatorial chemistry is based on the same principle as real chemistry—many different compounds can be generated from a few building blocks at once. The difference lies in its speed, as millions of compounds can be produced in a few seconds. On the other hand, many virtual screening methods, such as QSAR (Quantitative Sturcture-Activity Relationship), pharmacophore models, and molecular docking, have been developed to study these libraries. These models allow for the selection of molecules to be synthesized and tested with a high probability of success. The virtual combinatorial chemistry–virtual screening tandem has become a fundamental tool in the process of searching for and developing a drug, as it allows the process to be accelerated with extraordinary economic savings.     

多齿杂原子配体铬系乙烯三聚催化剂研究进展

按照多齿杂原子配体(含氧、氮、磷、硫以及混合氮磷和混合氮硫多齿配体)的分类,综述了不同铬系乙烯三聚催化剂体系的组成、活性及对1-己烯的总选择性,展望了乙烯三聚催化剂的商业应用前景。研究表明,配体结构对乙烯三聚活性和选择性的影响最为显著。Cr(Ⅲ)SNS催化体系因其原料价格低廉,合成收率高,活化所需甲基铝氧烷(MAO)用量低,同时具有对1-己烯的选择性和活性都很高的性能,将有很好的工业应用价值。     

Design of new catalysts for ecological high-quality transportation fuels by combinatorial computational chemistry and tight-binding quantum chemical molecular dynamics approaches

Recently, we introduced a concept of combinatorial chemistry to computational chemistry and proposed a new method called “combinatorial computational chemistry”, which enables us to perform a theoretical high-throughput screening of catalysts. In the present paper, we reviewed our recent application of our combinatorial computational chemistry approach to the design of new catalysts for high-quality transportation fuels. By using our combinatorial computational chemistry techniques, we succeeded to predict new catalysts for methanol synthesis and Fischer–Tropsch synthesis. Moreover, we have succeeded in the development of chemical reaction dynamics simulator based on our original tight-binding quantum chemical molecular dynamics method. This program realizes more than 5000 times acceleration compared to the regular first-principles molecular dynamics method. Electronic- and atomic-level information on the catalytic reaction dynamics at reaction temperatures significantly contributes the catalyst design and development. Hence, we also summarized our recent applications of the above quantum chemical molecular dynamics method to the clarification of the methanol synthesis dynamics in this review.     

A GC-based method for high-throughput screening of enantioselective catalysts

By combining two gas chromatography instruments (each containing a column with a chiral stationary phase) with the proper robotics and software, it is possible to construct an instrumental configuration which makes possible high-throughput screening of the enantioselectivity of a given catalytic reaction. As an example, the acylation-based catalytic kinetic resolution of racemic 2-phenyl-1-propanol catalyzed by mutant lipases can be about assayed, 700 exact E- and ee-determinations being possible per day. The method is, therefore, of interest in the directed evolution of enantioselective enzymes and/or in the combinatorial search for asymmetric transition metal catalysts.     

Rhodium‐Catalyzed Homogeneous Reductive Amidation of Aldehydes

The catalytic reductive amidation of an aldehyde (hexanal) with an amide (acetamide) is reported. Apart from the desired N‐hexylacetamide, the two isomeric unsaturated intermediates as well as hexanol are produced together with higher mass products that arise from aldol condensation and diamide coupling of the aldehyde. Screening of different catalyst precursor salts, ligands and reaction conditions led to the finding that the catalytic system based on the (cyclooctadiene)rhodium chloride dimer, [Rh(cod)Cl]₂, in combination with the ligand xantphos and an acid co‐catalyst results in high selectivity for the desired product. Under optimized conditions nearly full conversion is reached with high selectivity to the desired N‐alkylamide and with a very high N ‐ alkylamide/alcohol ratio, while producing only small amounts of by‐products. The scope of the reaction has been investigated using different amides as well as aldehydes; the results show the general applicability of this novel reaction, but with electron‐withdrawing amides the selectivity to N‐alkylamide is lower. NMR studies showed that the nucleophilic addition of acetamide to hexanal is acid catalyzed, forming N‐(1‐hydroxyhexyl)acetamide in equilibrium with both hexanal and the dehydrated unsaturated imides. A catalytic mechanism is proposed in which a strong acid such as HOTs acts as a co‐catalyst by establishing a rapid chemical equilibrium between the aldehyde, acetamide and the intermediates. Furthermore, it is proposed that the presence of acid causes a change in catalytic species, enabling a cationic Rh/xantphos hydrogenation catalyst to selectively hydrogenate the intermediates to N‐hexylacetamide in the presence of hexanal.     

Easily Accessible TADDOL‐Derived Bisphosphonite Ligands: Synthesis and Application in the Asymmetric Hydroformylation of Vinylarenes

The synthesis of chiral bidentate bisphosphonite ligands based on the TADDOL motif from readily available starting materials has been developed. Taking advantage of the modular nature of the building blocks, a diverse ligand library has been prepared. Their catalytic potential has been evaluated in the asymmetric hydroformylation of styrene and derivatives. These catalysts showed high activity and provided the aldehydes in high enantiomeric purity.

     

Recent advances in homogeneous and heterogeneous asymmetric catalysis with nitrogen–containing ligands

Nitrogen–containing chiral ligands are being used more and more in asymmetric catalysis. This article is an overview of results published in 1993--1996 in this field and tries to open new perspectives for this type of ligand, more particularly with the purpose of heterogenization of the catalytic systems. This revised version was published online in June 2006 with corrections to the Cover Date.     

Hybrid organic-inorganic solids for heterogeneous asymmetric catalysis

This paper provides a short review of recent progress in the design and synthesis of chiral organic–inorganic hybrid solids and their applications in heterogeneous asymmetric catalysis. Homochiral hybrid solids containing catalytic sites can be readily prepared by linking appropriately designed chiral bridging ligands with metal ion or metal cluster nodes. Heterogeneous asymmetric catalysts with enantioselectivity as high as 99.2 and turnover number (TON) as high as 20,000 have been obtained based on these hybrid organic–inorganic solids. The modular nature of the present approach promises to lead to a variety of practically useful heterogeneous asymmetric catalysts for many organic transformations.     

Advances in Catalyst Systems for the Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones

Hydrogenation of prochiral ketones using chiral transition-metal catalysts represents the cleanest way to access enantiomerically enriched secondary alcohols, which are important building blocks in fine chemicals synthesis. Despite excellent activity, selectivity and compatibility of metal complexes with variety of functional groups, no universal catalysts exist. In this article we summarize the advances in catalyst systems for the asymmetric homogenous and heterogenous hydrogenation of ketones that have been made in past decade. The development of catalysts is oriented in reaching as high as activity with low catalyst loadings, using “greener’’ conditions, and ensuring good recyclability of catalysts. Even though ruthenium complexes represent the largest part of the catalysts, other metals rapidly penetrate this field.     

Central nicotinic receptors: structure, function, ligands, and therapeutic potential

The growing interest in nicotinic receptors, because of their wide expression in neuronal and non-neuronal tissues and their involvement in several important CNS pathologies, has stimulated the synthesis of a high number of ligands able to modulate their function. These membrane proteins appear to be highly heterogeneous, and still only incomplete information is available on their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions; so far, only compounds showing selectivity between alpha4beta2 and alpha7 receptors have been obtained. The nicotinic receptor ligands have been designed starting from lead compounds from natural sources such as nicotine, cytisine, or epibatidine, and, more recently, through the high-throughput screening of chemical libraries. This review focuses on the structure of the new agonists, antagonists, and allosteric ligands of nicotinic receptors, it highlights the current knowledge on the binding site models as a molecular modeling approach to design new compounds, and it discusses the nAChR modulators which have entered clinical trials.     

Miniaturization of screening devices for the combinatorial development of heterogeneous catalysts

The present work is focused on the determination of the advantages, bottlenecks and challenges of miniaturized screening systems which are essential to the success of combinatorial high-throughput methodologies in heterogeneous catalysis. Two different reactor configurations with different degrees of miniaturization were developed for the parallel and fast screening of heterogeneously catalyzed gas phase reactions: a monolithic reactor system acting as a multichannel reactor and a microreaction system based on microfabrication techniques. In both cases, a scanning mass spectrometry technique was successfully applied for quantitative product analysis within 60 s per catalyst. Due to its flexibility and high spatial resolution, this three dimensional scanning MS can be used with different and highly parallel reactor arrays. Many experiments were carried out to study the efficiency and reliability of the different screening systems, with the oxidation of methane, the oxidation of CO, and the oxidative dehydrogenation of i-butane as model reactions. Moreover, chip modules in silicon–glass technology having a number of parallel microchannels were developed, each of them containing a different catalyst. Using this approach, “catalysis-on-a-chip” proved in methane oxidation was possible. Finally, a multibatch reactor consisting of a number of parallel mini autoclaves was developed and tested in the liquid-phase hydrogenation of citral in order to overcome the lack of parallel and fast screening procedures for heterogeneously catalyzed gas–liquid reactions widely spread in the chemical industry.