Reaction Rate Acceleration of Cooperative Catalytic Systems: Metal Nanoparticles and Lewis Acids in Arene Hydrogenation.

Employing two distinct catalysts in one reaction medium synergistically is a powerful strategy for activating less reactive substrates. Although the approach has been well-developed in homogeneous conditions, it remains challenging and rare in heterogeneous catalysis, especially under gas-liquid-solid multiphase reaction conditions. Here, we describe the development of cooperative and synergistic catalyst systems of heterogeneous Rh-Pt bimetallic nanoparticle catalysts, Rh-Pt/DMPSi-Al2 O3 , and Sc(OTf)3 in the liquid phase for the hydrogenation of arenes under very mild conditions. Dramatic rate acceleration was achieved with cooperative activation. Remarkably, more challenging substrates that contained strong electron-donating groups and sterically hindered substituents were smoothly hydrogenated. Mechanistic insights into the cooperative activation of an aromatic substrate by heterogeneous metal nanoparticles and a soluble Lewis acid was obtained by kinetic studies and by direct observation of 1 H and 45 Sc NMR spectra.

Chiral Rhodium Nanoparticle-Catalyzed Asymmetric Arylation Reactions.

The development of heterogeneous catalyst systems for enantioselective reactions is an important subject in modern chemistry as they can be easily separated from products and potentially reused; this is particularly favorable in achieving a more sustainable society. Whereas numerous homogeneous chiral small molecule catalysts have been developed to date, there are only limited examples of heterogeneous ones that maintain high activity and have a long lifetime. On the other hand, metal nanoparticle catalysts have attracted much attention in organic chemistry due to their robustness and ease of deposition on solid supports. Given these advantages, metal nanoparticles modified with chiral ligands, defined as "chiral metal nanoparticles", would work efficiently in asymmetric catalysis. Although asymmetric hydrogenation catalyzed by chiral metal nanoparticles was pioneered in the late twentieth century, the application of chiral metal nanoparticle catalysis for asymmetric C-C bond-forming reactions that give a high level of enantioselectivity with wide substrate scope was very limited.This Account summarizes recent investigations that we have carried out in the field of chiral rhodium (Rh) nanoparticle catalysis for asymmetric arylation reactions. We initially utilized composites of polystyrene-based copolymers with cross-linking moieties and carbon black incarcerated Rh nanoparticle catalysts for the asymmetric 1,4-addition of arylboronic acids to enones. We found that chiral diene-modified heterogeneous Rh nanoparticles were effective in these reactions, with excellent enantioselectivities and without causing metal leaching, and that bimetallic Rh/Ag nanoparticle catalysts enhanced activity. The catalyst could be easily recovered and reused more than ten times, thus demonstrating the robustness of metal nanoparticle catalysts.We then developed a secondary amide-substituted chiral diene modifier designed as a bifunctional ligand that possesses a metal biding site and a NH group to activate a substrate through hydrogen bonding. This chiral diene was very effective for the Rh/Ag nanoparticle-catalyzed asymmetric arylation of various electron-deficient olefins, including enones, unsaturated esters, unsaturated amides and nitroolefins, and imines to afford the corresponding products in excellent yields and with outstanding enantioselectivities. The system was also applicable for the synthesis of intermediates of various useful compounds. Furthermore, the compatibility of chiral Rh nanoparticles with other catalysts was confirmed, enabling the development of tandem reaction systems and cooperative catalyst systems.The nature of the active species was investigated. Several characteristic features of the heterogeneous nanoparticle systems that were completely different from those of the corresponding homogeneous metal complex systems were found.

Heterogeneous Supramolecular Catalysis through Immobilization of Anionic M4L6 Assemblies on Cationic Polymers.

Although most of the currently developed supramolecular catalysts that emulate enzymatic reactivity with unique selectivity and activity through specific host-guest interactions work under homogeneous conditions, enzymes in nature can operate under heterogeneous conditions as membrane-bound enzymes. In order to develop such a heterogeneous system, an immobilized chiral supramolecular cluster Ga416 (2) was introduced into cross-linked polymers with cationic functionalities. These heterogeneous supramolecular catalysts were used in aza-Prins and aza-Cope reactions and successfully applied to continuous-flow reactions. They showed high durability and maintained high turnovers for long periods of time. In sharp contrast to the majority of examples of heterogenized homogeneous catalysts, the newly developed catalysts showed enhanced activity and robustness compared to those exhibited by the corresponding soluble cluster catalyst. An enantioenriched cluster was also immobilized to enable asymmetric catalysis, and activity and enantioselectivity of the supported chiral catalyst were maintained during recovery and reuse experiments and under a continuous-flow process. Significantly, the structure of the ammonium cations in the polymers affected stability, reactivity, and enantioselectivity, which is consistent with the hypothesis that the cationic moieties in the polymer support interact with cluster as an exohedral protecting shell, thereby influencing their catalytic performance.

Direct Synthesis of Hydroquinones from Quinones through Sequential and Continuous-Flow Hydrogenation-Derivatization Using Heterogeneous Au-Pt Nanoparticles as Catalysts.

Pt-Au bimetallic nanoparticle catalysts immobilized on dimethyl polysilane (Pt-Au/(DMPSi-Al2 O3 )) have been developed for selective hydrogenation of quinones to hydroquinones. High reactivity, selectivity, and robustness of the catalysts were confirmed under continuous-flow conditions. Various direct derivatizations of quinones, such as methylation, acetylation, trifluoromethanesulfonylation, methacrylation, and benzoylation were successfully performed under sequential and continuous-flow conditions to afford the desired products in good to excellent yields. Especially, air-sensitive hydroquinones, such as anthrahydroquinones and naphthohydroquinones, could be successfully generated and derivatized under closed sequential and continuous-flow conditions without decomposition.

Polysilane-Immobilized Rh-Pt Bimetallic Nanoparticles as Powerful Arene Hydrogenation Catalysts: Synthesis, Reactions under Batch and Flow Conditions and Reaction Mechanism.

Hydrogenation of arenes is an important reaction not only for hydrogen storage and transport but also for the synthesis of functional molecules such as pharmaceuticals and biologically active compounds. Here, we describe the development of heterogeneous Rh-Pt bimetallic nanoparticle catalysts for the hydrogenation of arenes with inexpensive polysilane as support. The catalysts could be used in both batch and continuous-flow systems with high performance under mild conditions and showed wide substrate generality. In the continuous-flow system, the product could be obtained by simply passing the substrate and 1 atm H2 through a column packed with the catalyst. Remarkably, much higher catalytic performance was observed in the flow system than in the batch system, and extremely strong durability under continuous-flow conditions was demonstrated (>50 days continuous run; turnover number >3.4 × 105). Furthermore, details of the reaction mechanisms and the origin of different kinetics in batch and flow were studied, and the obtained knowledge was applied to develop completely selective arene hydrogenation of compounds containing two aromatic rings toward the synthesis of an active pharmaceutical ingredient.

Chiral Nanoparticles/Lewis Acids as Cooperative Catalysts for Asymmetric 1,4-Addition of Arylboronic Acids to α,ß-Unsaturated Amides.

Cooperative catalysts consisting of chiral Rh/Ag nanoparticles and Sc(OTf)3 have been developed that catalyze asymmetric 1,4-addition reactions of arylboronic acids with α,ß-unsaturated amides efficiently. The reaction has been considered one of the most challenging reactions because of the low reactivity of the amide substrates. The new catalysts provide the desired products with outstanding enantioselectivities (>98 % ee) in the presence of low loadings (<0.5 mol %) of the catalyst.

Chiral Metal Nanoparticle Systems as Heterogeneous Catalysts beyond Homogeneous Metal Complex Catalysts for Asymmetric Addition of Arylboronic Acids to α,ß-Unsaturated Carbonyl Compounds.

We describe the use of chiral metal nanoparticle systems, as novel heterogeneous chiral catalysts for the asymmetric 1,4-addition of arylboronic acids to α,ß-unsaturated carbonyl compounds, as representative C-C bond-forming reactions. The reactions proceeded smoothly to afford the corresponding ß-arylated products in high to excellent yields and outstanding enantioselectivities with wide substrate scope. Remarkably, the nanoparticle catalysts showed performance in terms of yield, enantioselectivity, and catalytic turnover that was superior to that of the corresponding homogeneous metal complexes. The catalyst can be successfully recovered and reused in a gram-scale synthesis with low catalyst loading without significant loss of activity. The nature of the active species was investigated, and we found that characteristic features of the nanoparticle system were totally different from those of the metal complex system.

Tandem oxidative processes catalyzed by polymer-incarcerated multimetallic nanoclusters with molecular oxygen.

Heterogeneous catalysis and one-pot tandem reactions are key for efficient and practical organic syntheses and for green and sustainable chemistry. Heterogeneous catalysts can be recovered and reused. These catalysts can be applied to efficient systems, such as continuous-flow systems. Tandem reactions often proceed via highly reactive but unstable intermediates. Tandem reactions do not require workup or much purification of the intermediate. This Account summarizes recent developments that we have made in the field of multifunctional heterogeneous metal nanocluster catalysts for use in tandem reactions based on aerobic oxidation reactions as key processes. We constructed our heterogeneous metal nanoclusters via two important procedures--microencapsulation and cross-linking--using polystyrene-based copolymers with cross-linking moieties. These frameworks can efficiently stabilize small metal nanoclusters to maintain high catalytic activity without aggregation and leaching of nanoclusters. Aggregation and leaching are prevented by weak but multiple interactions between metal nanocluster surfaces and benzene rings in the copolymer as well as by the physical envelopment of cross-linked polymer backbones. Small nanoclusters, including multimetallic alloy clusters (nanoalloys), can be "imprisoned" into these cross-linked polymer composites. The term we use for these processes is polymer incarceration. Direct oxidative esterifications were achieved with polymer-incarcerated (PI) Au nanocluster catalysts. Amides were synthesized from alcohols and amines under aerobic oxidative conditions with PI bimetallic nanocluster catalysts composed of Au and Fe-group metals that formed separated nanoclusters rather than alloys. Oxidative lactam formation from amino alcohols was also achieved. On the other hand, imines could be prepared selectively from alcohols and amines with PI Au-Pd bimetallic nanoclusters. We also achieved the integration of the aerobic oxidation of allylic alcohols and the following Michael reaction catalyzed by trimetallic PI catalysts containing Au-Pd alloy nanoclusters and tetraalkoxyborates as cross-linkers. All of these heterogeneous catalysts could be recovered by simple operations and reused without significant loss of activity or any leaching of metals. We have demonstrated that the polymer incarceration method enables the simultaneous immobilization of several metals, with which we can achieve one-pot tandem oxidative processes using molecular oxygen as an oxidant within the multifunctional heterogeneous catalysts. Suitable choices of metals and bimetallic structures are crucial for the reactivity and the selection of reaction pathways.

Chiral metal nanoparticle-catalyzed asymmetric C-C bond formation reactions.

Chiral ligand-modified metal nanoparticles possess an attractive potential for application in asymmetric synthesis. This article focuses on chiral-nanoparticle-catalyzed asymmetric C-C bond formation reactions and discusses the nature of the active species.

Size of gold nanoparticles driving selective amide synthesis through aerobic condensation of aldehydes and amines.

Metal nanoparticles (NPs) have attracted much attention in many fields due to their intrinsic characteristics. It is generally accepted that smaller NPs (1.5-3 nm) are more active than larger NPs, and reverse cases are very rare. We report here the direct aerobic oxidative amide synthesis from aldehydes and amines catalyzed by polymer-incarcerated gold (Au) NPs. A unique correlation between imine/amide selectivity and size of NPs was discovered; Au-NPs of medium size (4.5-11 nm) were found to be optimal. High yields were obtained with a broad range of substrates, including primary amines. Au-NPs of medium size could be recovered and reused several times without loss of activity, and they showed good activity and selectivity in amide formation from alcohols and amines.

Self-Assembled Nanocomposite Organic Polymers with Aluminum and Scandium as Heterogeneous Water-Compatible Lewis Acid Catalysts.

While water-compatible Lewis acids have great potential as accessible and environmentally benign catalysts for various organic transformations, efficient immobilization of such Lewis acids while keeping high activity and without leaching of metals even under aqueous conditions is a challenging task. Self-assembled nanocomposite catalysts of organic polymers, carbon black, aluminum reductants, and scandium salts as heterogeneous water-compatible Lewis acid catalysts are described. These catalysts could be successfully applied to various C-C bond-forming reactions without leaching of metals. Scanning transmission electron microscopy analyses revealed that the nanocomposite structure of Al and Sc was fabricated in these heterogeneous catalysts. It is noted that Al species, which are usually decomposed rapidly in the presence of water, are stabilized under aqueous conditions.

Copolymer-incarcerated nickel nanoparticles with N-heterocyclic carbene precursors as active cross-linking agents for Corriu-Kumada-Tamao reaction.

We have developed heterogeneous polymer-incarcerated nickel nanoparticles (NPs), which catalyze cross-coupling reactions. The matrix structure of these catalysts incorporates both N-heterocyclic carbenes (NHCs) as ligands and Ni-NPs, thanks to a new design of cross-linking agents in polymer supports. These embedded NHCs were detected by field gradient swollen-resin magic angle spinning NMR analysis. They were successfully applied to Corriu-Kumada-Tamao reactions with a broad substrate scope including functional group tolerance, and the catalyst could be recovered and reused several times without loss of activity.

Selective Detection of Toxic C1 Chemicals Using a Hydroxylamine-Based Chemiresistive Sensor Array.

Formaldehyde (FA) is a deleterious C1 pollutant commonly found in the interiors of modern buildings. C1 chemicals are generally more toxic than the corresponding C2 chemicals, but the selective discrimination of C1 and C2 chemicals using simple sensory systems is usually challenging. Here, we report the selective detection of FA vapor using a chemiresistive sensor array composed of modified hydroxylamine salts (MHAs, ArCH2ONH2·HCl) and single-walled carbon nanotubes (SWCNT). By screening 32 types of MHAs, we have identified an ideal sensor array that exhibits a characteristic response pattern for FA. Thus, trace FA (0.02-0.05 ppm in air) can be clearly discriminated from the corresponding C2 chemical, acetaldehyde (AA). This system has been extended to discriminate methanol (C1) from ethanol (C2) in combination with the catalytic conversion of these alcohols to their corresponding aldehydes. Our system offers portable and reliable chemical sensors that discriminate the subtle differences between C1 and C2 chemicals, enabling advanced environmental monitoring and healthcare applications.

Polymer-incarcerated chiral Rh/Ag nanoparticles for asymmetric 1,4-addition reactions of arylboronic acids to enones: remarkable effects of bimetallic structure on activity and metal leaching.

Robust and highly active bimetallic Rh nanoparticle (NP) catalysts, PI/CB Rh/Ag, have been developed and applied to the asymmetric 1,4-addition of arylboronic acids to enones without leaching of the metals. We found that the structures of the bimetallic Rh/Ag catalysts and chiral ligands strongly affect their catalytic activity and the amount of metal leaching. PI/CB Rh/Ag could be recycled several times by simple operations while keeping high yields and excellent enantioselectivities. To show the versatility of the PI/CB Rh/Ag catalyst, a one-pot, oxidation-asymmetric 1,4-addition reaction of an allyl alcohol and an arylboronic acid was demonstrated by combining the PI/CB Rh/Ag catalyst with PI/CB Au as an aerobic oxidation catalyst.

Discovery of a metalloenzyme-like cooperative catalytic system of metal nanoclusters and catechol derivatives for the aerobic oxidation of amines.

We have discovered a new class of cooperative catalytic system, consisting of heterogeneous polymer-immobilized bimetallic Pt/Ir alloyed nanoclusters (NCs) and 4-tert-butylcatechol, for the aerobic oxidation of amines to imines under ambient conditions. After optimization, the desired imines were obtained in good to excellent yields with broad substrate scope. The reaction rate was determined to be first-order with respect to the substrate and catechol and zero-order for the alloyed Pt/Ir NC catalyst. Control studies revealed that both the heterogeneous NC catalyst and 4-tert-butylcatechol are essential and act cooperatively to facilitate the aerobic oxidation under mild conditions.

Hydrogen Generation from Organic Hydrides under Continuous-Flow Conditions Using Polymethylphenylsilane-Aluminum Immobilized Platinum Catalyst.

Hydrogen is an important resource for realizing the goal of a hydrogen-based society as well as for synthetic organic chemistry. Catalytic dehydrogenation of organic hydrides such as methyl cyclohexane is attractive for hydrogen storage and transportation in terms of reversibility and selectivity of catalytic reactions and hydrogen storage density. We developed a highly active polymethylphenylsilane-aluminum immobilized platinum catalyst (Pt/MPPSi-Al2 O3 ) for dehydrogenation of organic hydrides. Organic hydrides were fully converted into the corresponding aromatic compounds under reactive distillation conditions at 200 °C or under circulation-flow conditions using the Pt/MPPSi-Al2 O3 catalyst packed in a column at 260 °C. The dehydrogenation reaction reached a maximum conversion at equilibrium (ca. 60%) under continuous-flow conditions at 260 °C. This catalytic continuous-flow dehydrogenation was applied to a formal hydrogen transfer from organic hydrides to unsaturated organic substrates under sequential and continuous-flow conditions for practical flow hydrogenation reactions by connecting two different heterogeneous catalysts packed in columns.

Polymer-incarcerated gold-palladium nanoclusters with boron on carbon: a mild and efficient catalyst for the sequential aerobic oxidation-Michael addition of 1,3-dicarbonyl compounds to allylic alcohols.

We have developed a polymer-incarcerated bimetallic Au-Pd nanocluster and boron as a catalyst for the sequential oxidation-addition reaction of 1,3-dicarbonyl compounds with allylic alcohols. The desired tandem reaction products were obtained in good to excellent yields under mild conditions with broad substrate scope. In the course of our studies, we discovered that the excess reducing agent, sodium borohydride, reacts with the polymer backbone to generate an immobilized tetravalent boron catalyst for the Michael reaction. In addition, we found bimetallic Au-Pd nanoclusters to be particularly effective for the aerobic oxidation of allylic alcohols under base- and water-free conditions. The ability to conduct the reaction under relatively neutral and anhydrous conditions proved to be key in maintaining good catalyst activity during recovery and reuse of the catalyst. Structural characterization (STEM, EDS, SEM, and N(2) absorption/desorption isotherm) of the newly prepared PI/CB-Au/Pd/B was performed and compared to PI/CB-Au/Pd. We found that while boron was important for the Michael addition reaction, it was found to alter the structural profile of the polymer-carbon black composite material to negatively affect the allylic oxidation reaction.

Powerful amide synthesis from alcohols and amines under aerobic conditions catalyzed by gold or gold/iron, -nickel or -cobalt nanoparticles.

Considering the importance of the development of powerful green catalysts and the omnipresence of amide bonds in natural and synthetic compounds, we report here on reactions between alcohols and amines for amide bond formation in which heterogeneous gold and gold/iron, -nickel, or -cobalt nanoparticles are used as catalysts and molecular oxygen is used as terminal oxidant. Two catalysts show excellent activity and selectivity, depending on the type of alcohols used. A wide variety of alcohols and amines, including aqueous ammonia and amino acids, can be used for the amide synthesis. Furthermore, the catalysts can be recovered and reused several times without loss of activity.

Copper-catalyzed, aerobic oxidative cross-coupling of alkynes with arylboronic acids: remarkable selectivity in 2,6-lutidine media.

Aerobic oxidative cross-coupling reactions between alkynes and boronic acids under mild conditions catalyzed by low loadings of a copper salt are reported. 2,6-Lutidine accelerated the reactions dramatically, and the desired coupling products were obtained in high yields with high selectivities.

Remarkable effect of bimetallic nanocluster catalysts for aerobic oxidation of alcohols: combining metals changes the activities and the reaction pathways to aldehydes/carboxylic acids or esters.

Selective oxidation of alcohols catalyzed by novel carbon-stabilized polymer-incarcerated bimetallic nanocluster catalysts using molecular oxygen has been developed. The reactivity and the selectivity were strongly dependent on the combination of metals and solvent systems; aldehydes and ketones were obtained by the gold/platinum catalyst in benzotrifluoride, and esters were formed by the gold/palladium catalyst in methanol. To the best of our knowledge, this is the first example that the reaction pathway has been changed dramatically in gold catalysis by combining with a second metal. The differences in the activity and the selectivity are considered to be derived from the difference in the structure of the bimetallic clusters.