Control of selectivity in heterogeneous catalysis by tuning nanoparticle properties and reactor residence time.

A combination of the advantages of homogeneous and heterogeneous catalysis could enable the development of sustainable catalysts with novel reactivity and selectivity. Although heterogeneous catalysts are often recycled more easily than their homogeneous counterparts, they can be difficult to apply in traditional organic reactions and modification of their properties towards a desired reactivity is, at best, complex. In contrast, tuning the properties of homogeneous catalysts by, for example, modifying the ligands that coordinate a metal centre is better understood. Here, using olefin cyclopropanation reactions catalysed by dendrimer-encapsulated Au nanoclusters as examples, we demonstrate that changing the dendrimer properties allows the catalytic reactivity to be tuned in a similar fashion to ligand modification in a homogeneous catalyst. Furthermore, we show that these heterogeneous catalysts employed in a fixed-bed flow reactor allow fine control over the residence time of the reactants and thus enables the control over product distribution in a way that is not easily available for homogeneous catalysts.

A Pt-cluster-based heterogeneous catalyst for homogeneous catalytic reactions: X-ray absorption spectroscopy and reaction kinetic studies of their activity and stability against leaching.

The design and development of metal-cluster-based heterogeneous catalysts with high activity, selectivity, and stability under solution-phase reaction conditions will enable their applications as recyclable catalysts in large-scale fine chemicals production. To achieve these required catalytic properties, a heterogeneous catalyst must contain specific catalytically active species in high concentration, and the active species must be stabilized on a solid catalyst support under solution-phase reaction conditions. These requirements pose a great challenge for catalysis research to design metal-cluster-based catalysts for solution-phase catalytic processes. Here, we focus on a silica-supported, polymer-encapsulated Pt catalyst for an electrophilic hydroalkoxylation reaction in toluene, which exhibits superior selectivity and stability against leaching under mild reaction conditions. We unveil the key factors leading to the observed superior catalytic performance by combining X-ray absorption spectroscopy (XAS) and reaction kinetic studies. On the basis of the mechanistic understandings obtained in this work, we also provide useful guidelines for designing metal-cluster-based catalyst for a broader range of reactions in the solution phase.

Stereocontrolled total syntheses of isodomoic acids G and H via a unified strategy.

Marine neuroexcitatory compounds isodomoic acids G and H were efficiently synthesized from a common intermediate using a silicon-based cross-coupling reaction. Dividing each target compound into the core fragment and the side-chain fragment enabled the synthesis to be convergent. The trans-2,3-disubstituted pyrrolidine core fragment was accessed through a diastereoselective rhodium-catalyzed carbonylative silylcarbocyclization reaction of a vinylglycine-derived 1,6-enyne. A stereochemically divergent desilylative iodination reaction was developed to convert the cyclization product to both E- and Z-alkenyl iodides, which would eventually lead to isodomoic acid G and isodomoic acid H, respectively. The late-stage alkenyl-alkenyl silicon-based cross-coupling reaction uniting the core alkenyl iodides and the side-chain alkenylsilanol was achieved under mild conditions. Finally, two mild deprotections afforded the target molecules.

Highly active heterogeneous palladium nanoparticle catalysts for homogeneous electrophilic reactions in solution and the utilization of a continuous flow reactor.

A highly active heterogeneous Pd-nanoparticle catalyst for the intramolecular addition of phenols to alkynes was developed and employed in a continuous flow reaction system. Running the reaction in flow mode revealed reaction kinetics, such as the activation energy and catalyst deactivation, and provides many potential practical advantages.

Total syntheses of isodomoic acids G and H.

The total syntheses of marine natural products belonging to the kainoid family, isodomoic acids G and H, are described. The strategic connection involves a sequential silylcarbocyclization/silicon-based cross-coupling process. These total syntheses were achieved efficiently via a 12- and a 13-step, longest-linear sequence, respectively. The key transformations include a diastereoselective rhodium-catalyzed carbonylative silylcarbocyclization reaction of an (l)-vinylglycine-derived 1,6-enyne, a desilylative iodination reaction, as well as an alkenyl-alkenyl silicon-based cross-coupling reaction. The mechanistic insight garnered during the investigation of the iododesilylation reaction enabled stereocontrolled introduction of the iodine with either inversion or retention of double bond configuration. The invertive desilylative iodination leads to the total synthesis of isodomoic acid H, while its congener, isodomoic acid G, was obtained via a retentive iododesilylation.

Sequential silylcarbocyclization/silicon-based cross-coupling reactions.

A sequential rhodium-catalyzed silylcarbocyclization of enynes parlayed with a palladium-catalyzed, silicon-based cross-coupling reaction has been developed for the synthesis of highly substituted cyclopentanes. 1,6-Enynes reacted with benzyldimethylsilane in the presence of rhodium catalysts to afford five-membered rings bearing a (Z)-alkylidenylbenzylsilyl group. A variety of substitution patterns and heteroatom substituents were compatible. The silylcarbocyclization in which an unsaturated ester participated was also achieved. The resulting alkylidenylsilanes underwent palladium-catalyzed cross-coupling using tetra-n-butylammonium fluoride. This cross-coupling reaction displayed a broad substrate scope. A wide variety of substitution patterns, electronic properties, and heteroatoms were compatible. All of the cross-coupling reactions proceeded in high yields under very mild conditions and with complete retention of double bond configuration, resulting in densely functionalized 3-(Z)-benzylidenecyclopentanes and heterocycles.

MgI(2)-mediated ring expansions of secondary methylenecyclopropyl amides.

Ring expansion of secondary methylenecyclopropyl amides in the presence of MgI2 was investigated. Various isomeric five-membered unsaturated lactams were obtained, depending on the character of the substituent Q. The amide group served as a nucleophile in ring closing as well as an activator for ring opening. In the presence of a variety of aryl aldimines or aldehydes, alkylative ring expansion occurred in a single step under mild and neutral conditions leading to gamma'-amino- or -hydroxy-alkylated pyrrol-2-ones. Also, it was shown that a 4-methylpyrrol-2-one could be transformed to a gamma-hydroxy-alkylated product by the use of a direct vinylogous aldol reaction.