Bifunctional Heterogeneous Catalysis of Silica–Alumina‐Supported Tertiary Amines with Controlled Acid–Base Interactions for Efficient 1,4‐Addition Reactions

We report the first tunable bifunctional surface of silica–alumina‐supported tertiary amines (SA–NEt₂) active for catalytic 1,4‐addition reactions of nitroalkanes and thiols to electron‐deficient alkenes. The 1,4‐addition reaction of nitroalkanes to electron‐deficient alkenes is one of the most useful carbon–carbon bond‐forming reactions and applicable toward a wide range of organic syntheses. The reaction between nitroethane and methyl vinyl ketone scarcely proceeded with either SA or homogeneous amines, and a mixture of SA and amines showed very low catalytic activity. In addition, undesirable side reactions occurred in the case of a strong base like sodium ethoxide employed as a catalytic reagent. Only the present SA‐supported amine (SA–NEt₂) catalyst enabled selective formation of a double‐alkylated product without promotions of side reactions such as an intramolecular cyclization reaction. The heterogeneous SA–NEt₂ catalyst was easily recovered from the reaction mixture by simple filtration and reusable with retention of its catalytic activity and selectivity. Furthermore, the SA–NEt₂ catalyst system was applicable to the addition reaction of other nitroalkanes and thiols to various electron‐deficient alkenes. The solid‐state magic‐angle spinning (MAS) NMR spectroscopic analyses, including variable‐contact‐time ¹³C cross‐polarization (CP)/MAS NMR spectroscopy, revealed that acid–base interactions between surface acid sites and immobilized amines can be controlled by pretreatment of SA at different temperatures. The catalytic activities for these addition reactions were strongly affected by the surface acid–base interactions.     

手性自负载催化剂研究新进展

催化剂的负载和回收再利用是提高其使用效率、降低反应成本和减少金属离子对产物污染的一条有效途径。与传统的负载模式不同, 手性自负载催化剂通过含双或多官能团的手性配体与金属通过自组装形成一类有机-无机聚合物,因此无需使用任何载体,即能够有效地实现手性催化剂的回收和再利用。近年来,手性自负载催化剂作为一种新的负载模式,已经成功地应用于一些非均相催化的不对称反应中。本文概述了手性自负载催化剂的在一些不对称催化反应研究中取得的新进展。     

In situ solid-state NMR for heterogeneous catalysis: a joint experimental and theoretical approach

In situ solid-state NMR is a well-established tool for investigations of the structures of the adsorbed reactants, intermediates and products on the surface of solid catalysts. The techniques allow identifications of both the active sites such as acidic sites and reaction processes after introduction of adsorbates and reactants inside an NMR rotor under magic angle spinning (MAS). The in situ solid-state NMR studies of the reactions can be achieved in two ways, i.e. under batch-like or continuous-flow conditions. The former technique is low cost and accessible to the commercial instrument while the latter one is close to the real catalytic reactions on the solids. This critical review describes the research progress on the in situ solid-state NMR techniques and the applications in heterogeneous catalysis under batch-like and continuous-flow conditions in recent years. Some typical probe molecules are summarized here to detect the Br?nsted and Lewis acidic sites by MAS NMR. The catalytic reactions discussed in this review include methane aromatization, olefin selective oxidation and olefin metathesis on the metal oxide-containing zeolites. With combining the in situ MAS NMR spectroscopy and the density functional theoretical (DFT) calculations, the intermediates on the catalyst can be identified, and the reaction mechanism is revealed. Reaction kinetic analysis in the nanospace instead of in the bulk state can also be performed by employing laser-enhanced MAS NMR techniques in the in situ flow mode (163 references).     

Acid-base catalysis of chiral Pd complexes: development of novel catalytic asymmetric reactions and their application to synthesis of drug candidates

Using the unique character of the chiral Pd complexes 1 and 2, highly efficient catalytic asymmetric reactions have been developed. In contrast to conventional Pd(0)-catalyzed reactions, these complexes function as an acid-base catalyst. Thus active methine and methylene compounds were activated to form chiral palladium enolates, which underwent enantioselective carbon-carbon bond-forming reactions such as Michael reaction and Mannich-type reaction with up to 99% ee. Interestingly, these palladium enolates acted cooperatively with a strong protic acid, formed concomitantly during the formation of the enolates to activate electrophiles, thereby promoting the C-C bond-forming reaction. This palladium enolate chemistry was also applicable to electrophilic enantioselective fluorination reactions, and various carbonyl compounds including beta-ketoesters, beta-ketophosphonates, tert-butoxycarbonyl lactone/lactams, cyanoesters, and oxindole derivatives could be fluorinated in a highly enantioselective manner (up to 99% ee). Using this method, the catalytic enantioselective synthesis of BMS-204352, a promising anti-stroke agent, was achieved. In addition, the direct enantioselective conjugate addition of aromatic and aliphatic amines to alpha,beta-unsaturated carbonyl compound was successfully demonstrated. In this reaction, combined use of the Pd complex 2 having basic character and the amine salt was the key to success, allowing controlled generation of the nucleophilic free amine. This aza-Michael reaction was successfully applied to asymmetric synthesis of the CETP inhibitor torcetrapib.     

镁铝酸碱双功能氧化物催化剂上醇胺氧化耦合合成亚胺性能（英文）

亚胺是一类重要的含氮有机化合物,由于具有不饱和C=N双键,可以作为一种有效的氮源,用于一系列含氮衍生物的合成.目前合成亚胺的工艺路线主要是通过羰基化合物和一级胺在强酸条件下缩合;与该路线相比,醇和胺在空气或氧气存在条件下耦合是一条更为绿色的工艺路线,其副产物只有水产生.目前的报道表明,一些具有氧化还原性质的催化剂,如负载型贵金属催化剂和负载型过渡金属氧化物催化剂在该反应中表现出一定催化性能,但很少关注表面酸碱性质对该反应性能的影响.在本工作中,我们尝试将具有酸碱双功能性质的Mg-Al复合氧化物作为催化剂用于该反应中,考察了Mg/Al比、焙烧温度和后处理条件对催化性能的影响.结果显示,Mg/Al=3的催化剂在反应中表现出最优的催化活性;NH_3-TPD和CO_2-TPD显示,随着镁含量的增加,样品表面碱性中心的数量呈现出先增加后减少的趋势,其中Mg/Al=3的样品表面酸、碱总量最大,而且该样品表面弱碱中心数量也最多;我们通过焙烧和探针分子吸附等后处理手段进一步调控了催化剂表面的酸碱性质,初步结果表明在酸碱中心的协同作用下可以有效地催化醇和胺的氧化耦合反应;其中弱碱性位可能是活化醇的主要活性中心,而醇的氧化是该反应的速控步骤,因此可以推测表面弱碱中心的数量在一定程度上决定着催化剂在该反应中的性能.     

Exploring Guanidinium Organocatalysts for Hypoiodite-Mediated Reactions

This account describes our recent work on developing guanidinium hypoiodite- catalysts for oxidative carbon-nitrogen and carbon-carbon bond-forming reactions. These reactions proceeded smoothly using guanidinium hypoiodite generated in situ by treating 1,3,4,6,7-hexahydro-2H-pyrimido[1,2-a]pyrimidine hydroiodide salts with an oxidant. In this approach, the ionic interaction and hydrogen bonding ability of the guanidinium cations enable bond-forming reactions that have been difficult with conventional methods. Enantioselective oxidative carbon-carbon bond-forming reaction was also achieved by using a chiral guanidinium organocatalyst.     

Palladium-catalyzed cross-coupling reactions in total synthesis

In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.     

The polymer incarcerated method for the preparation of highly active heterogeneous palladium catalysts

A new method named "the polymer incarcerated (PI) method" for preparing a heterogeneous palladium catalyst has been developed. The method is operationally simple, and the Pd catalyst prepared (PI Pd) is highly active for hydrogenation, carbon-carbon, and carbon-oxygen bond-forming reactions. Remarkable points are that the activity of PI Pd is higher than that of homogeneous Pd catalysts and that PI Pd is recovered by simple filtration and reused several times without loss of activity. The catalyst is expected to replace many heterogeneous palladium catalysts, especially Pd/C, which is often used in academia and industry, but recovery of which is difficult.     

固体酸催化剂结构与催化反应机理的核磁共振研究

Solid acid catalysts have been widely used in advanced petrochemical processes because of their environmental friendliness, high product selectivity, and easy product separation. Solid-state nuclear magnetic resonance (NMR) spectroscopy is a well-established tool for structure determination and dynamic study of various functional materials. In this review, we focus mainly on our research using solid-state NMR to characterize the acid properties and elucidate the catalytic reaction mechanism of solid acid catalysts. The acid strength of solid acids can be quantitatively measured from the chemical shifts of adsorbed probe molecules such as pyridine, acetone, trialkylphosphine oxides, and trimethylphosphine. The spatial proximity and synergetic effect of various acid sites on solid acid catalysts can be ascertained by two-dimensional (2D) double-quantum magic angle spinning (DQ MAS) NMR spectroscopy. Additionally, in situ solid-state NMR spectroscopy can be used to explore heterogeneous catalytic reaction mechanisms by monitoring the evolution of the reactants, intermediates, and products.     

Visible-light-driven Hydroamination of Alkynes over a New Type of Activated Carbon Immobilized Cu2+ Photocatalyst

A new type of activated carbon immobilized copper(Cu/AC) photocatalyst was prepared by a facile impregnation-adsorption method, where Cu²⁺ is chemically adsorbed by abundant oxygenated functional groups on large-surface-area activated carbon surface. Cu/AC exhibited good activity and selectivity to imine for the hydro-amination of alkynes at 60℃ under visible light irradiation. The reaction is initialized by the activation of alkynes molecules at Cu active sites with the aid of light as evidenced by the solid-state NMR and laser photolysis measurements and the control experiments. This strategy for catalyst design is potentially extended to the immobilization of other metal homogeneous catalysts for various heterogeneous catalytic systems.     

Monomeric metal aqua complexes in the interlayer space of montmorillonites as strong Lewis acid catalysts for heterogeneous carbon-carbon bond-forming reactions

Montmorillonite-enwrapped copper and scandium catalysts (Cu(2+)- and Sc(3+)-monts) were easily prepared by treating Na(+)-mont with the aqueous solution of the copper nitrate and scandium triflate, respectively. The resulting Cu(2+)- and Sc(3+)-monts showed outstanding catalytic activities for a variety of carbon-carbon bond-forming reactions, such as the Michael reaction, the Sakurai-Hosomi allylation, and the Diels-Alder reaction, under solvent-free or aqueous conditions. The remarkable activity of the mont catalysts is attributable to the negatively charged silicate layers that are capable of stabilizing metal cations. Furthermore, these catalysts were reusable without any appreciable loss in activity and selectivity. The Cu(2+)-mont-catalyzed Michael reaction proceeds via a ternary complex in which both the 1,3-dicarbonyl compound and the enone are coordinated to a Lewis acid Cu(2+) center.     

酸碱双功能MgO/HMCM-22催化剂上Knoevenagel缩合反应

采用浸渍法制备了一系列MgO改性催化剂MgO/HMCM-22, 利用X射线衍射、N₂物理吸附-脱附、扫描电镜、傅里叶变换红外光谱、NH₃及CO₂程序升温脱附等技术对所制催化剂进行了表征. 结果表明, MgO改性后MCM-22分子筛仍保持原有的结构; 随着MgO负载量的增加, 催化剂的碱强度和碱含量显著增加, 而强酸含量明显减少, 弱酸酸位有所增加. 以Knoevenagel缩合为探针反应, 考察了所制催化剂的性能. 在优化的反应条件下, MgO/HMCM-22上苯甲醛转化率高达92.6%. 催化剂 MgO/HMCM-22和MgO/NaMCM-22的催化性能明显优于HMCM-22和MgO. 酸中心和碱中心均对该缩合反应起着重要的促进作用. MgO/HMCM-22对Knoevenagel缩合反应显示出较高的催化活性, 体现出明显的酸碱协同催化作用.     

Noncovalently supported heterogeneous chiral amine catalysts for asymmetric direct aldol and Michael addition reactions

A new strategy for the immobilization of asymmetric organocatalysts by combining polystyrene (PS)/sulfonic acids and chiral amines in situ through acid-base interactions is presented. The PS/sulfonic acids play a dual role as catalyst anchors and modulators for activity and stereoselectivity. Different types of polymeric sulfonic acids were examined and 1% divinylbenzene (DVB) cross-linked PS/sulfonic acid 1 e with a medium loading of sulfonic acid moieties was found to be the optimal support. Furthermore, the noncovalency of this system allows combinatorial screening of optimal catalysts for the targeted reactions. In this regard, highly efficient and enantioselective heterogeneous catalysts were identified for the asymmetric direct aldol and Michael addition reactions. The catalysts could be easily recovered by filtration and reused for six cycles with similar stereoselectivity but slightly decreased activity. Significantly, the deactivated catalysts could be regenerated following an acidic washing/amine recharging procedure.     

Bridging the gap between homogeneous and heterogeneous catalysis: ortho/para H(2) conversion, hydrogen isotope scrambling, and hydrogenation of olefins by Ir(CO)Cl(PPh(3))(2)

Some transition metal complexes are known to catalyze ortho/para hydrogen conversion, hydrogen isotope scrambling, and hydrogenation reactions in liquid solution. Using the example of Vaska's complex, we present here evidence by NMR that the solvent is not necessary for these reactions to occur. Thus, solid frozen solutions or polycrystalline powdered samples of homogeneous catalysts may become heterogeneous catalysts. Comparative liquid- and solid-state studies provide novel insight into the reaction mechanisms.     

The Co‐Entrapment of a Homogeneous Catalyst and an Ionic Liquid by a Sol–gel Method: Recyclable Ionogel Hydrogenation Catalysts

Molecular hydrogenation catalysts have been co‐entrapped with the ionic liquid [Bmim]NTf₂ inside a silica matrix by a sol–gel method. These catalytic ionogels have been compared to simple catalyst‐doped glasses, the parent homogeneous catalysts, commercial heterogeneous catalysts, and Rh‐doped mesoporous silica. The most active ionogel has been characterised by transmission electron microscopy, X‐ray photoelectron spectroscopy, and solid state NMR before and after catalysis. The ionogel catalysts were found to be remarkably active, recyclable and resistant to chemical change.     

Surface reactions of 4-aminothiophenol with heterobifunctional crosslinkers bearing both succinimidyl ester and maleimide for biomolecular immobilization

Surface reactions of 4-aminothiophenol (4-ATP) with a series of heterogeneous crosslinkers containing both maleimide and succinimidyl ester groups were investigated with infrared reflection absorption spectroscopy (IRRAS) and X-ray photoelectron spectroscopy (XPS). Two types of surface reactions exist: (1) for most crosslinkers, a dominant reaction of amine and succinimidyl ester gave homogeneous maleimide-pendant surfaces; (2) for other crosslinkers, a side reaction between amine and maleimide, accompanying the main reaction, yielded heterogeneous surfaces with two linking groups, maleimide and succinimidyl ester. A typical example for the second case is the reaction of surface amines with N-succinimidyl-6-maleimidylhexanoate (SMH). Finally, a peptide, H-Gly-Arg-Gly-Asp-Ser-Pro-Cys-OH (GRGDSPC), was immobilized on the SMH-derived surface as a bridging structure through two linkages, cysteine thioether and glycine amide.     

Cooperative Acid–Base Effects with Functionalized Mesoporous Silica Nanoparticles: Applications in Carbon–Carbon Bond‐Formation Reactions

Acid–base bifunctional mesoporous silica nanoparticles (MSN) were prepared by a one‐step synthesis by co‐condensation of tetraethoxysilane (TEOS) and silanes possessing amino and/or sulfonic acid groups. Both the functionality and morphology of the particles can be controlled. The grafted functional groups were characterized by using solid‐state ²⁹Si and ¹³C cross‐polarization/magic angle spinning (CP/MAS) NMR spectroscopy, thermal analysis, and elemental analysis, whereas the structural and the morphological features of the materials were evaluated by using XRD and N₂ adsorption–desorption analyses, and SEM imaging. The catalytic activities of the mono‐ and bifunctional mesoporous hybrid materials were evaluated in carbon–carbon coupling reactions like the nitroaldol reaction and the one‐pot deacetalization–nitroaldol and deacetalization–aldol reactions. Among all the catalysts evaluated, the bifunctional sample containing amine and sulfonic acid groups (MSN–NNH₂–SO₃H) showed excellent catalytic activity, whereas the homogeneous catalysts were unable to initiate the reaction due to their mutual neutralization in solution. Therefore a cooperative acid–base activation is envisaged for the carbon–carbon coupling reactions.     

Metalloporphyrin‐Based Hypercrosslinked Polymers Catalyze Hetero‐Diels–Alder Reactions of Unactivated Aldehydes with Simple Dienes: A Fascinating Strategy for the Construction of Heterogeneous Catalysts

We describe a novel and intriguing strategy for the construction of efficient heterogeneous catalysts by hypercrosslinking catalyst molecules in a one‐pot Friedel–Crafts alkylation reaction. The new hypercrosslinked polymers (HCPs) as porous solid catalysts exhibit the combined advantages of homogeneous and heterogeneous catalysis, owing to their high surface area, good stability, and tailoring of catalytic centers on the frameworks. Indeed, a new class of metalloporphyrin‐based HCPs were successfully synthesized using modified iron(III) porphyrin complexes as building blocks, and the resulting networks were found to be excellent recyclable heterogeneous catalysts for the hetero‐Diels–Alder reaction of unactivated aldehydes with 1,3‐dienes. Moreover, this new strategy showed wide adaptability, and many kinds of homogeneous‐like solid‐based catalysts with high catalytic performance and excellent recyclability were also constructed.     

Self-supported heterogeneous titanium catalysts for enantioselective carbonyl-ene and sulfoxidation reactions

A new strategy for the heterogenization of chiral titanium complexes was developed by the in situ assembly of bridged multitopic BINOL ligands with [Ti(OiPr)4] without using a support. The assembled heterogeneous catalysts (self-supported) showed excellent enantioselectivity in both the carbonyl-ene reaction of alpha-methylstyrene with ethyl glyoxylate (up to 98 % ee) and the oxidation of sulfides (up to >99 % ee). The catalytic performance of these heterogeneous catalytic systems was comparable or even superior to that attained with their homogeneous counterparts. The spacers between the two BINOL units of the ligands in the assembled catalysts had significant impact on the enantioselectivity of the carbonyl-ene reaction. This demonstrates the importance of the supramolecular structures of the assemblies on their catalytic behavior. In the catalysis of sulfoxidation, the self-supported heterogeneous titanium catalysts were highly stable and could be readily recycled and reused for over one month (at least eight cycles) without significant loss of activity and enantioselectivity (up to >99.9 % ee). The features of these self-supported catalysts, such as facile preparation, robust chiral structure of solid-state catalysts, high density of the catalytically active units in the solids, as well as easy recovery and simple recycling, are particularly important in developing methods for the synthesis of optically active compounds in industrial processes.     

Synergistic Effect of NiLDH@YZ Hybrid and Mechanochemical Agitation on Glaser Homocoupling Reaction

Herein, we report the synthesis of nickel-layered double hydroxide amalgamated Y-zeolite (NiLDH@YZ) hybrids and the evaluation of the synergistic effect of various NiLDH@YZ catalysts and mechanochemical agitation on Glaser homocoupling reactions. Nitrogen adsorption-desorption experiments were carried out to estimate the surface area and porosity of NiLDH@YZ hybrids. The basicity and acidity of these hybrids were determined by CO₂-TPD and NH₃-TPD experiments respectively and this portrayed good acid-base bifunctional feature of the catalysts. The NiLDH@YZ-catalyzed mechanochemical Glaser coupling reaction achieved best yield of 83 % for the 0.5NiLDH@0.5YZ hybrid after 60 min of agitation, which revealed the highest acid-base bifunctional feature compared to all the investigated catalysts. The developed catalyst has proven itself as a robust and effective candidate that can successfully be employed up to four catalytic cycles without significant loss in catalytic activity, under optimized reaction conditions. This work demonstrated a new strategy for C−C bond formation enabled by the synergy between mechanochemistry and heterogeneous catalysis.