Supramolecular control on chemo- and regioselectivity via encapsulation of (NHC)-Au catalyst within a hexameric self-assembled host

The encapsulation of a Au(I) catalyst within a self-assembled, hydrogen bonded, hexameric capsule dramatically changes its catalytic activity, leading to unusual products due to the steric requirements of the host's cavity.     

Supramolecular catalysis of unimolecular rearrangements: substrate scope and mechanistic insights

A cavity-containing metal-ligand assembly is employed as a catalytic host for the 3-aza Cope rearrangement of allyl enammonium cations. Upon binding, the rates of rearrangement are accelerated for all substrates studied, up to 850-fold. Activation parameters were measured for three enammonium cations in order to understand the origins of acceleration. Those parameters reveal that the supramolecular structure is able to reduce both the entropic and enthalpic barriers for rearrangement and is highly sensitive to small structural changes of the substrate. The space-restrictive cavity preferentially binds closely packed, preorganized substrate conformations, which resemble the conformations of the transition states. This hypothesis is also supported by quantitative NOE studies of two encapsulated substrates, which place the two reacting carbon atoms in close proximity. The capsule can act as a true catalyst, since release and hydrolysis facilitate catalytic turnover. The question of product hydrolysis was addressed through detailed kinetic studies. We conclude that the iminium product must dissociate from the cavity interior and the assembly exterior before hydroxide-mediated hydrolysis, and propose the intermediacy of a tight ion pair of the polyanionic host with the exiting product.     

Supramolecular control on reactivity and selectivity inside the confined space of H-bonded hexameric capsules

The confinement of substrates inside the cavity of self-assembled capsules makes it possible to effectively catalyze organic reactions in a way that is analogous to how enzymes work in biological systems. Due to steric constraints, solvent exclusion, intermediates stabilization, and conformational control of substrates, chemical reactions taking place in a confined space may exhibit unique processes. As a result, the fundamental rules of organic reactivity are frequently broken. The hexameric capsule C_R, an intriguing supramolecular assembly formed by six resorcinarene 1 macrocycles and eight water molecules, is the subject of this review. This assembly has proven to be effective at catalyzing several chemical reactions by controlling reactivity and selectivity in its confined space.     

Effector Regulated Catalytic Cyclization of Alkynoic Acids Using Pt2L4 Cages

Metabolic pathways are highly regulated by effector molecules that influences the rate of enzymatic reactions. Inspired by the catalytic regulation found in living cells, we report a Pt₂L₄ cage of which the activity can be controlled by effectors that bind inside the cage. The cage shows catalytic activity in the lactonization of alkynoic acids, with the reaction rates dependent on the effector guest bound in the cage. Some effector guests enhance the rate of the lactonization by up to 19-fold, whereas one decreases it by 5-fold. When mixtures of specific substrates are used, both starting materials and products act as guests for the Pt₂L₄ cage, enhancing its catalytic activity for one substrate while reducing its activity for the other. The reported regulatory behavior obtained by the addition of effector molecules paves the way to the development of more complex, metabolic-like catalyst systems.     

Synergic Interplay Between Halogen Bonding and Hydrogen Bonding in the Activation of a Neutral Substrate in a Nanoconfined Space

The principle of amplified halogen bonding (XB) in a small space is exploited as a catalytic tool for the activation of an XB acceptor substrate in a nanoconfined environment. The inner cavity of the resorcinarene capsule has been equipped with an XB catalyst bearing an ammonium unit acting as a Trojan horse to drive the catalyst inside the capsule. In the presence of a specific XB catalyst, the capsule is able to catalyze a Michael reaction between N‐methylpyrrole and methyl vinyl ketone. In the bulk medium in absence of the resorcinarene capsule, the XB catalyst is catalytically ineffective. Quantum‐mechanical investigations highlight that the Michael reaction proceeds through the activation of the carbonyl group by synergistically enhanced halogen/hydrogen‐bonding interactions and takes place in an open pentameric capsule.     

Urea-Functionalized Fe4L6 Cages for Supramolecular Gold Catalyst Encapsulation to Control Substrate Activation Modes

The excellent catalytic performances of enzymes in terms of activity and selectivity are an inspiration for synthetic chemists and this has resulted in the development of synthetic containers for supramolecular catalysis. In such containers the local environment and pre-organization of catalysts and substrates leads to control of the activity and selectivity of the catalyst. Herein we report a supramolecular strategy to encapsulate single catalysts in a urea-functionalized Fe₄L₆ cage, which can co-encapsulate a functionalized urea substrate through hydrogen bonding. Distinguished selectivity is obtained, imposed by the cage as site isolation only allows catalysis through π activation of the substrate and as a result the selectivity is independent of catalyst concentration. The encapsulated catalyst is more active than the free analogue, an effect that can be ascribed to transitionstate stabilization rather than substrate pre-organization, as revealed by the MM kinetic data. The simple strategy reported here is expected to be of general use in many reactions, for which the catalyst can be functionalized with a sulfonate group required for encapsulation.     

Development of atom-economical catalytic asymmetric reactions under proton transfer conditions: construction of tetrasubstituted stereogenic centers and their application to therapeutics

The development of atom-economical catalytic asymmetric reactions based on two distinct sets of catalyst, a rare earth metal/amide-based ligand catalyst and a soft Lewis acid/hard Br?nsted base catalyst, is reviewed. These catalytic systems exhibit high catalytic activity and stereoselectivity by harnessing a cooperative catalysis through hydrogen bond/metal coordination and soft-soft interactions/hard-hard interactions, respectively. The effectiveness of these cooperative catalysts is clearly delineated by the high stereoselectivity in reactions with highly coordinative substrates, and the specific activation of otherwise low-reactive pronucleophiles under proton transfer conditions. The rare earth metal/amide-based ligand catalyst was successfully applied to catalytic asymmetric aminations, nitroaldol (Henry) reactions, Mannich-type reactions, and conjugate addition reactions, generating stereogenic tetrasubstituted centers. Catalytic asymmetric amination and anti-selective catalytic asymmetric nitroaldol reactions were successfully applied to the efficient enantioselective synthesis of therapeutic candidates, such as AS-3201 and the β(3)-adrenoreceptor agonist, showcasing the practical utility of the present protocols. The soft Lewis acid/hard Br?nsted base cooperative catalyst was specifically developed for the chemoselective activation of soft Lewis basic allylic cyanides and thioamides, which are otherwise low-reactive pronucleophiles. The cooperative action of the catalyst allowed for efficient catalytic generation of active carbon nucleophiles in situ, which were integrated into subsequent enantioselective additions to carbonyl-type electrophiles.     

Recent Advances in Multifunctional Capsule Catalysts in Heterogeneous Catalysis?

Capsule catalysts composed of pre-shaped core catalysts and layer zeolites have been widely used in the tandem reactions where multiple continuous reactions are combined into one process. They show excellent catalytic performance in heterogeneous catalysis, including the direct synthesis of middle isoparaffins or dimethyl ether from syngas, as compared to the conventional hybrid catalysts. The present review highlights the recent development in the design of capsule catalysts and their catalytic applications in heterogeneous catalysis. The capsule catalyst preparation methods are introduced in detail, such as hydrothermal synthesis method, dual-layer method, physically adhesive method and single crystal crystallization method. Furthermore, several new applications of capsule catalysts in heterogeneous catalytic processes are presented such as in the direct synthesis of liquefied petroleum gas from syngas, the direct synthesis of para-xylene from syngas and methane dehydroaromatization. In addition, the development in the design of multifunctional capsule catalysts is discussed, which makes the capsule catalyst not just a simple combination of two different catalysts, but has some special functions such as changing the surface hydrophobic or acid properties of the core catalysts. Finally, the future perspectives of the design and applications of capsule catalysts in heterogeneous catalysis are provided.     

Dual effect of halides in the Stille reaction: in situ halide metathesis and catalyst stabilization

Halide anions can increase or decrease the transmetallation rate of the Stille reaction through in situ halide metathesis. Although the influence of the halogen present in oxidative addition complexes on the transmetallation rate with organostannanes was already known, the application of in situ halide metathesis to accelerate cross-coupling reactions with organometallic reagents is not described in the literature yet. In addition a second unprecedented role of halides was discovered. Halide anions stabilize the [Pd(0)(L)(2)] catalyst in Stille reactions, by means of [Pd(0)X(L)(2)](-) formation (X=Cl, I), hereby preventing its leaching from the catalytic cycle. Both arene (iodobenzene) and azaheteroarene (2-halopyridine, halopyrazine, 2-halopyrimidine) substrates were used.     

Solvent-free,microwave-assisted highly efficient,rapid and simple synthesis of biphenyl compounds by using silica based Pd(II) catalyst

To maintain catalytic performance of any catalyst for a long time, the selection of support material is a very important parameter for heterogeneous catalytic systems, and this performance makes the catalyst valuable. In view of its low cost and availability, silica can be considered as a good support material for transition metal ions in the cross coupling reactions. Therefore, this study describes i) silica-gel based palladium catalyst with a long-term catalytic performance, ii) rapid, simple, economic, and green procedure which was developed for Suzuki reactions. The catalyst showed superior reusability (ten runs) and catalytic efficiency against coupling reactions under mild conditions (50°C, 5 min and air atmosphere). Moreover, the catalyst gave partially good reaction yields with aril chlorides which have poor activity in coupling reactions. In addition, an excellent turnover number (TON: 66000) and frequency (TOF: 825000) were obtained using very small catalyst loading (1.5 × 10^?3 mol %). This paper concludes that silica-gel based Pd(II) catalyst and the protocol of synthesis of biaryls were suitable for coupling reactions.     

Mild Friedel–Crafts Reactions inside a Hexameric Resorcinarene Capsule: C−Cl Bond Activation through Hydrogen Bonding to Bridging Water Molecules

A novel catalytic feature of a hexameric resorcinarene capsule is highlighted. The self‐assembled cage was exploited to promote the Friedel–Crafts benzylation of several arenes and heteroarenes with benzyl chloride under mild conditions. Calculations showed that there are catalytically relevant hydrogen‐bonding interactions between the bridging water molecules of the capsule and benzyl chloride, which is fundamental for the activation of the C?Cl bond. The capsule controls the reaction outcome. Inside the inner cavity of the capsule, N‐methylpyrrole is preferentially benzylated in the unusual β‐position while mesitylene reacts faster than 1,3‐dimethoxybenzene despite the greater π‐nucleophilicity of the latter compound.     

Biochar as heterogeneous support for immobilization of Pd as efficient and reusable biocatalyst in C–C coupling reactions

Biochar is a stable and carbon‐rich solid which has a high density of carbonyl, hydroxyl and carboxylic acid functional groups on its surface. In this work, the surface of biochar nanoparticles (BNPs) was modified with 3‐choloropropyltrimtoxysilane and further 2‐(thiophen‐2‐yl)‐1H‐benzo[d]imidazole was anchored on its surface. Then, palladium nanoparticles were fabricated on the surface of the modified BNPs and further the catalytic application was studied as recyclable biocatalyst in carbon–carbon coupling reactions such as Suzuki–Miyaura and Heck–Mizoroki cross‐coupling reactions. The structure of the catalyst was characterized using scanning electron microscopy, transmission electron microscopy, energy‐dispersive X‐ray spectroscopy, thermogravimetric analysis, X‐ray diffraction and atomic absorption spectroscopy. The catalyst can be reused several times without a decrease in its catalytic efficiency. In addition to the several advantages reported, application of biochar as catalyst support for the first time is a major novelty of the present work.     

Open air palladium catalyzed cyanation—the use of PMHS to protect from oxygen

PMHS (polymethylhydrosiloxane) used in catalytic amounts has a remarkable ability to prevent catalyst poisoning by oxygen contamination during palladium catalyzed cyanation reactions. The procedure is applicable to a wide range of substrates and is so effective that it allows the reactions to be run fully open to the atmosphere.     

Selective Catalytic Synthesis of 1,2- and 8,9-Cyclic Limonene Carbonates as Versatile Building Blocks for Novel Hydroxyurethanes

The selective catalytic synthesis of limonene-derived monofunctional cyclic carbonates and their subsequent functionalisation via thiol–ene addition and amine ring-opening is reported. A phosphotungstate polyoxometalate catalyst used for limonene epoxidation in the 1,2-position is shown to also be active in cyclic carbonate synthesis, allowing a two-step, one-pot synthesis without intermittent epoxide isolation. When used in conjunction with a classical halide catalyst, the polyoxometalate increased the rate of carbonation in a synergistic double-activation of both substrates. The cis isomer is shown to be responsible for incomplete conversion and by-product formation in commercial mixtures of 1,2-limomene oxide. Carbonation of 8,9-limonene epoxide furnished the 8,9-limonene carbonate for the first time. Both cyclic carbonates underwent thiol–ene addition reactions to yield linked di-monocarbonates, which can be used in linear non-isocyanate polyurethanes synthesis, as shown by their facile ring-opening with N-hexylamine. Thus, the selective catalytic route to monofunctional limonene carbonates gives straightforward access to monomers for novel bio-based polymers.     

Simple, efficient catalyst system for the palladium-catalyzed amination of aryl chlorides, bromides, and triflates

Palladium complexes supported by (o-biphenyl)P(t-Bu)(2) (3) or (o-biphenyl)PCy(2) (4) are efficient catalysts for the catalytic amination of a wide variety of aryl halides and triflates. Use of ligand 3 allows for the room-temperature catalytic amination of many aryl chloride, bromide, and triflate substrates, while ligand 4 is effective for the amination of functionalized substrates or reactions of acyclic secondary amines. The catalysts perform well for a large number of different substrate combinations at 80-110 degrees C, including chloropyridines and functionalized aryl halides and triflates using 0.5-1.0 mol % Pd; some reactions proceed efficiently at low catalyst levels (0.05 mol % Pd). These ligands are effective for almost all substrate combinations that have been previously reported with various other ligands, and they represent the most generally effective catalyst system reported to date. Ligands 3 and 4 are air-stable, crystalline solids that are commercially available. Their effectiveness is believed to be due to a combination of steric and electronic properties that promote oxidative addition, Pd-N bond formation, and reductive elimination.     

Supported copper precatalysts for ligand-free, palladium-free Sonogashira coupling reactions

Copper(II) oxide and Cu metal, highly dispersed on inert oxides (silica, alumina), have been employed as precatalysts in ligand-free, palladium-free Sonogashira coupling reactions. Best results were obtained with highly dispersed Cu metal on alumina, which exhibited high reactivity with aryl iodides. Electron-rich alkynes, in particular arylacetylenes, act as the most effective alkyne substrates. The present catalytic system appears attractive in view of its ease of application and low cost, due to the use of a readily available non-noble metal catalyst combined with the absence of ligands.     

Studies on the Heck reaction with alkenyl phosphates: can the 1,2-migration be controlled? Scope and limitations

A catalyst system was identified which promotes the Heck coupling of nonactivated vinyl phosphates with electron deficient alkenes providing a new entry to diene products from simple and readily accessible starting materials. In contrast to our earlier work exploiting P(t-Bu)3 as the ligand in the presence of PdCl2(COD), the application of Buchwald's dialkylbiarylphosphines, X-Phos, effectively promoted the vinylic substitution with a wide range of alkenyl phosphates in the presence of 10 equiv of lithium chloride. Importantly, these reaction conditions suppressed 1,2-migration of the alkenyl palladium(II) intermediate. Further studies are also reported with the catalytic system which encourages isomerization in order to determine the range of vinyl phosphates that may participate in these coupling reactions. The extent of the 1,2-migration was dependent on the C1-substituent where best results were noted for substrates possessing a C1-alkyl quaternary carbon. Hence, with certain members of this class of alkenyl phosphates either the migrated or nonmigrated Heck products may be preferentially synthesized by selection of the phosphine ligand. Finally, competition experiments between an unactivated aryl chloride and a vinyl phosphate with a palladium catalyst possessing either X-Phos or P(t-Bu)3 as ligand demonstrated the ability to carry out Heck coupling reactions selectively with the aryl halide. Oxidative addition of the metal catalyst into the aryl chloride bond rather than the C-O bond of the alkenyl phosphate is therefore preferred.     

A theoretical study on the mechanism of the reductive half-reaction of xanthine oxidase

On the basis of the crystal structure of an aldehyde oxidoreductase, Huber et al. proposed a catalytic mechanism for the reductive half-reaction of xanthine oxidase which involves nucleophilic addition of Mo-bound hydroxide (Moco 1) to the substrate and hydride transfer from the substrate to sulfido group (Mo=S). Density functional theory calculations have been carried out for the oxidation of formaldehyde, acetaldehyde, formamide, and formamidine with Moco 2 to understand more detailed catalytic pathways. Our calculation results indicate that the anionic catalyst model acts as a nucleophile and is reactive for the oxidation of aldehyde substrates, which are reactive for nucleophilic addition. In these cases, a concerted mechanism is found to be more favorable than a stepwise mechanism. The concerted mechanism is further shown to be promoted by the presence of a nearby water molecule, in the active site, which serves as a Lewis acid for the nucleophilic addition of hydroxide. For less reactive formamide and formamidine (a model for xanthine) substrates, the calculated activation energies with the above mechanisms are high. These reactions also do not benefit from the presence of the water molecule. The results indicate that different catalyst forms might be responsible for the oxidation of different substrates, which could be regulated by the enzyme active site environment.     

β-环糊精超分子催化剂用于液相有机合成

详细介绍了β-环糊精超分子作为催化剂应用于液相有机合成, 包括开环、脱保护、保护、氧化、还原、加成、置换等反应的研究进展. 对β-环糊精的催化性能和反应底物选择性能进行分析, 认为β-环糊精与底物的相互作用可有效地催化液相有机化学反应, 提高反应选择性. 提出对β-环糊精进行功能化修饰将促使其在液相有机合成反应中有更大的发展前景.     

离子液体功能化金属/共价-有机框架材料在催化反应中应用

离子液体（ILs）功能化的金属有机框架（MOFs）和共价有机框架（COFs）材料兼具离子液体和MOFs/COFs的优点，是一种极具潜力的复合催化材料。MOFs和COFs材料固定的孔结构及较大的比表面积为负载高分散催化中心提供了天然的物理空间；多孔结构促使催化剂与反应物充分接触；丰富的孔道有利于运输催化反应底物和产物，进而实现催化反应的高效进行。特别是离子液体片段的引入，可以作为催化活性中心的配体（稳定剂）或分散剂，同时能够有效改善MOFs和COFs材料孔道和活性中心周围的微环境。此外，还可以充分利用离子液体片段在适当的反应条件下转化为氮杂环卡宾配体的特点，在MOFs和COFs材料中引入氮杂环卡宾有机金属配合物。因此，我们对近几年来离子液体功能化的MOFs或COFs催化体系在CO2环加成、CO2还原、C-C偶联、羰基化以及其它有机转化反应中的研究应用进行简要综述。并对复合材料在催化领域的发展进行总结和展望。