The concept of flow “fine” synthesis, that is, high yielding and selective organic synthesis by flow methods, is described. Some examples of flow “fine” synthesis of natural products and APIs are discussed. Flow methods have several advantages over batch methods in terms of environmental compatibility, efficiency, and safety. However, synthesis by flow methods is more difficult than synthesis by batch methods. Indeed, it has been considered that synthesis by flow methods can be applicable for the production of simple gasses but that it is difficult to apply to the synthesis of complex molecules such as natural products and APIs. Therefore, organic synthesis of such complex molecules has been conducted by batch methods. On the other hand, syntheses and reactions that attain high yields and high selectivities by flow methods are increasingly reported. Flow methods are leading candidates for the next generation of manufacturing methods that can mitigate environmental concerns toward sustainable society.

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,β-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.

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,β-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.

This microreview summarizes examples of Hf(OTf)₄-mediated or -catalyzed organic reactions. Hafnium triflate possesses four strongly electron-withdrawing OTf groups, together with an ionic radius of intermediate range (Al < Ti < Hf, Zr < Sc < Ln), and has an oxophilic hard character typical of group IV metals. This Lewis acid shows outstanding performance in catalytic Friedel–Crafts acylation reactions and Mannich-type reactions of imines, hydrazones, and N,O-acetals. Several natural products have also been synthesized by use of Hf(OTf)₄-mediated or -catalyzed reactions. Moreover, Hf(OTf)₄ has a number of potent features in carbohydrate syntheses. Hf(OTf)₄ possesses many unique characteristics that distinguish it from other Lewis acids. The unique characteristics of Hf(OTf)₄ should make this compound a major candidate for selection as a Lewis acid in the future.

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 CC 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.

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.

The copper(II)-catalyzed aerobic oxidative coupling reaction between aryl boronic acids and aniline derivatives was found to be improved significantly under visible-light-mediated photoredox catalysis. The substrate scope of this oxidative Chan–Lam reaction was thus expanded to include electron-deficient aryl boronic acids as viable starting materials.

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 CC 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.

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.

The copper(II)-catalyzed aerobic oxidative coupling reaction between aryl boronic acids and aniline derivatives was found to be improved significantly under visible-light-mediated photoredox catalysis. The substrate scope of this oxidative Chan–Lam reaction was thus expanded to include electron-deficient aryl boronic acids as viable starting materials.

The reductive formylation of amines using CO₂ and hydrosilanes is an attractive method for incorporating CO₂ into valuable organic compounds. However, previous systems required either high catalyst loadings or high temperatures to achieve high efficiency, and the substrate scope was mostly limited to simple amines. To address these problems, a series of alkyl bridged chelating bis(NHC) rhodium complexes (NHC=N-heterocyclic carbene) have been synthesized and applied to the reductive formylation of amines using CO₂ and Ph₂SiH₂. A rhodium-based bis(tzNHC) complex (tz=1,2,3-triazol-5-ylidene) was identified to be highly effective at a low catalyst loading and ambient temperature, and a wide substrate scope, including amines with reducible functional groups, were compatible.

The reductive formylation of amines using CO₂ and hydrosilanes is an attractive method for incorporating CO₂ into valuable organic compounds. However, previous systems required either high catalyst loadings or high temperatures to achieve high efficiency, and the substrate scope was mostly limited to simple amines. To address these problems, a series of alkyl bridged chelating bis(NHC) rhodium complexes (NHC=N-heterocyclic carbene) have been synthesized and applied to the reductive formylation of amines using CO₂ and Ph₂SiH₂. A rhodium-based bis(tzNHC) complex (tz=1,2,3-triazol-5-ylidene) was identified to be highly effective at a low catalyst loading and ambient temperature, and a wide substrate scope, including amines with reducible functional groups, were compatible.

The development of catalytic asymmetric carbon–carbon bond-forming reactions of alkylnitriles that do not have an activating group at the α-position, under proton-transfer conditions, is a challenging research topic. Here, we report catalytic asymmetric direct-type 1,4-addition reactions of alkylnitriles with α,β-unsaturated amides by using a catalytic amount of potassium hexamethyldisilazide (KHMDS) with a chiral macro crown ether. The desired reactions proceeded in high yields with good diastereo- and enantioselectivities. To our knowledge, this is the first example of catalytic asymmetric direct-type 1,4-addition reaction of alkylnitriles without any activating group at the α-position.

Enzymes exhibit overwhelmingly superior catalysis compared with artificial catalysts. Current strategies to rival enzymatic catalysis require unmodified or minimally modified structures of active sites, gigantic molecular weight, and sometimes the use of harsh conditions such as extremely low temperatures in organic solvents. Herein, we describe a design of small molecules that act as the simplest metalloenzyme-like catalysts that can function in water, without mimicking enzyme structures. These artificial catalysts efficiently promoted enantioselective direct-type aldol reactions using aqueous formaldehyde. The reactions followed Michaelis–Menten kinetics, and heat-resistant asymmetric environments were constructed in water.

We developed poly(dimethyl)silane-supported Pd catalysts that are readily prepared from Pd(OAc)₂, poly(dimethyl)silane, and Al₂O₃. The immobilization was achieved for the first time with a support that does not contain benzene rings. The Pd catalyst thus prepared was found to have higher hydrogenation activity than Pd/C. Furthermore, the catalyst was used in continuous-flow hydrogenation with various substrates, including simple liquid substrates (neat) and dissolved solid substrates. Vegetable oils, squalenes, and phosphatidylcholine were successfully hydrogenated on gram to kilogram scales.

A well-defined zinc antimonate salt was found to be an effective bifunctional catalyst that enables formal α-CH bond functionalization of glycine derivatives via a sequential aerobic oxidation and allylation reaction.

A copper-catalyzed multicomponent coupling reaction between in situ generated ortho-arynes, terminal alkynes, and carbon dioxide was developed to access isocoumarins in moderate to good yields. The key to this CO₂-incorporating reaction was the use of a versatile N-heterocyclic carbene/copper complex that was able to catalyze multiple transformations within the three-component reaction.

A copper-catalyzed multicomponent coupling reaction between in situ generated ortho-arynes, terminal alkynes, and carbon dioxide was developed to access isocoumarins in moderate to good yields. The key to this CO₂-incorporating reaction was the use of a versatile N-heterocyclic carbene/copper complex that was able to catalyze multiple transformations within the three-component reaction.

We have developed Cu^II-catalyzed enantioselective conjugate-addition reactions of boron to α,β-unsaturated carbonyl compounds and α,β,γ,δ-unsaturated carbonyl compounds in water. In contrast to the previously reported Cu^I catalysis that required organic solvents, chiral Cu^II catalysis was found to proceed efficiently in water. Three catalyst systems have been exploited: cat. 1: Cu(OH)₂ with chiral ligand L1; cat. 2: Cu(OH)₂ and acetic acid with ligand L1; and cat. 3: Cu(OAc)₂ with ligand L1. Whereas cat. 1 is a heterogeneous system, cat. 2 and cat. 3 are homogeneous systems. We tested 27 α,β-unsaturated carbonyl compounds and an α,β-unsaturated nitrile compound, including acyclic and cyclic α,β-unsaturated ketones, acyclic and cyclic β,β-disubstituted enones, acyclic and cyclic α,β-unsaturated esters (including their β,β-disubstituted forms), and acyclic α,β-unsaturated amides (including their β,β-disubstituted forms). We found that cat. 2 and cat. 3 showed high yields and enantioselectivities for almost all substrates. Notably, no catalysts that can tolerate all of these substrates with high yields and high enantioselectivities have been reported for the conjugate addition of boron. Heterogeneous cat. 1 also gave high yields and enantioselectivities with some substrates and also gave the highest TOF (43 200 h⁻¹) for an asymmetric conjugate-addition reaction of boron. In addition, the catalyst systems were also applicable to the conjugate addition of boron to α,β,γ,δ-unsaturated carbonyl compounds, although such reactions have previously been very limited in the literature, even in organic solvents. 1,4-Addition products were obtained in high yields and enantioselectivities in the reactions of acyclic α,β,γ,δ-unsaturated carbonyl compounds with diboron 2 by using cat. 1, cat. 2, or cat. 3. On the other hand, in the reactions of cyclic α,β,γ,δ-unsaturated carbonyl compounds with compound 2, whereas 1,4-addition products were exclusively obtained by using cat. 2 or cat. 3, 1,6-addition products were exclusively produced by using cat. 1. Similar unique reactivities and selectivities were also shown in the reactions of cyclic trienones. Finally, the reaction mechanisms of these unique conjugate-addition reactions in water were investigated and we propose stereochemical models that are supported by X-ray crystallography and MS (ESI) analysis. Although the role of water has not been completely revealed, water is expected to be effective in the activation of a borylcopper(II) intermediate and a protonation event subsequent to the nucleophilic addition step, thereby leading to overwhelmingly high catalytic turnover.

Since the discovery of the Mukaiyama aldol reaction in 1973, tremendous efforts have been made to develop a definitive catalyst that catalyzes asymmetric Mukaiyama aldol reactions under mild conditions with broad substrate tolerance. Forty years later, an exhaustive search for a water-compatible Lewis acid was able to uncover the hidden potential of iron(II) and bismuth(III), leading to the establishment of broadly applicable and versatile catalytic systems for asymmetric Mukaiyama aldol reactions in aqueous media. The ternary catalytic system was able to expand the substrate generality considerably as the most distinguished catalyst ever reported. The superiority of this methodology over conventional methods has also been demonstrated in terms of high catalytic activity, simplicity of experimental procedures, and a wide substrate range including aqueous aldehydes, for which the stereochemistry had been regarded as difficult to control. Furthermore, a facile synthesis of the chiral ligand underscores its versatility. The reaction did not proceed at all without use of water. In the postulated mechanism, water plays prominent roles in: (1) producing the active metal complexes with a high water-exchange rate constant (3.2 × 10⁶) to activate substrates effectively and to catalyze the reaction through a rapid proton transfer on the order of picoseconds; (2) facilitating the catalytic turnover with simultaneous desilylation as direct access to aldol adducts or facile recovery of active metal complexes; and (3) stabilizing rigid transition states composed of metal complexes and reactants through entropy-driven aggregation derived from the highest cohesive energy density.

A current trend in organic chemistry is the development of highly efficient, environmentally friendly and inexpensive catalysts for asymmetric transformations. Alkaline earth metals, due to their specific chemical properties and abundance in nature, provide promising and challenging catalysts in organic synthesis. This article describes the utilization of alkaline earth metals in the development of an effective catalytic system based on calcium salts in combination with Box-type ligands. We disclose asymmetric 1,4-addition and [3+2] cycloaddition reactions using simple catalytic systems consisting of calcium chloride dihydrate, chiral ligands and tetramethylguanidine. Various Box ligands were synthesized and the most effective proved to be that bearing an indane chiral backbone and a cyano group. Depending on the structure of both glycine Schiff bases and α,β-unsaturated compounds, the corresponding Michael adducts or pyrrolidine derivatives were obtained in moderate to high yields with high enantioselectivities. Modification of the catalytic system by using more Lewis acidic calcium salts such as calcium triflate and neutral Pybox-type ligands allows a tuning of the chemoselectivity and leads to suppression of the [3+2] cycloadition reactions. Various β-substituted acrylates provided 1,4-addition adducts exclusively in high yields with moderate to high diastereo- and enantioselectivities. This methodology has broadened a synthetic route to β-branched glutamic acid derivatives and established calcium salts as useful and attractive catalysts for asymmetric catalysis.

The efficient catalytic allylation of ketones, imines, and hydrazones with allylboronates using a catalytic amount of zinc amide is reported. In this reaction, the boron-to-zinc exchange process occurred smoothly to afford the corresponding allylzinc amides, and the desired allylation reactions proceeded in high efficiency (∼0.1 mol%). A mechanistic study revealed that transmetalation was a rate-determining step in the catalytic cycle, and also that the amide ligand on the zinc center played a key role in preparing reactive allylzinc species. Catalytic asymmetric allylations were also investigated, and high enantioselectivities were obtained using chiral diamine ligands.

The use of copper(0) powder in water enables chiral induction as well as high catalytic activity. Water plays a prominent role to determine both the catalytic activity and enantioselection. Elevated temperature is indispensable for the regular reaction pathway, and an active species tends to aggregate after the completion of the reaction. Selective deuteration implies enantiofacial differentiation of the deuteron toward an O-enolate intermediate. Strict substrate specificity suggests the vital interaction between copper(0) and an enone. A very weak isotope effect is indicative of instantaneous protonation. Accordingly, a redox copper cycle (0II) is tentatively proposed, in which transmetalation of a cyclometalated enone with diboron would furnish a boron enolate, followed by hydrolysis and reductive elimination. However, a single electron transfer process cannot be excluded on the available evidence and a more detailed mechanistic study is under way.

Catalytic asymmetric carbon–carbon bond-forming reactions provide one of the most efficient ways to synthesize optically active compounds, and, accordingly, many chiral catalysts for these reactions have been developed in the past two decades. However, the efficiency of the catalysts in terms of turnover number (TON) is often lower than that of some other reactions, such as asymmetric hydrogenation, and this has been one of the obstacles for industrial applications. Although there are some difficulties in increasing the efficiency, the issues might be solved by using continuous flow in the presence of chiral heterogeneous catalysts. Indeed, continuous-flow systems have several advantages over conventional batch systems. Here we summarize the recent progress in asymmetric CC bond-forming reactions under continuous-flow conditions with chiral heterogeneous catalysts.

Katalytische asymmetrische Kohlenstoff-Kohlenstoff-Kupplungen bieten einen der effizientesten Wege zu optisch aktiven Verbindungen, und entsprechend wurden in den vergangenen zwanzig Jahren viele chirale Katalysatoren für diese Reaktionen entwickelt. Diese Katalysatoren sind, beispielsweise gemessen an ihrer Umsatzzahl (TON), oft weniger effizient als Katalysatoren in anderen Reaktionen, z. B. asymmetrischen Hydrierungen, was eines der Hindernisse für die industrielle Anwendung darstellte. Es existieren zwar einige Schwierigkeiten bei der Effizienzsteigerung, diese können aber durch den Einsatz von kontinuierlichem Durchfluss in Gegenwart chiraler Heterogenkatalysatoren gelöst werden. In der Tat haben kontinuierliche Durchflusssysteme einige Vorteile gegenüber herkömmlichen Batchsystemen. Wir fassen hier die neuen Fortschritte bei asymmetrischen C-C-Kupplungen unter kontinuierlichen Durchflussbedingungen in Gegenwart chiraler Heterogenkatalysatoren zusammen.

We have developed asymmetric Mukaiyama aldol reactions of silicon enolates with aldehydes catalyzed by chiral Fe^II and Bi^III complexes. Although previous reactions often required relatively harsh conditions, such as strictly anhydrous conditions, very low temperatures (−78 °C), etc., the reactions reported herein proceeded in the presence of water at 0 °C. To find appropriate chiral water-compatible Lewis acids for the Mukaiyama aldol reaction, many Lewis acids were screened in combination with chiral bipyridine L1, which had previously been found to be a suitable chiral ligand in aqueous media. Three types of chiral catalysts that consisted of a Fe^II or Bi^III metal salt, a chiral ligand (L1), and an additive have been discovered and a wide variety of substrates (silicon enolates and aldehydes) reacted to afford the desired aldol products in high yields with high diastereo- and enantioselectivities through an appropriate selection of one of the three catalytic systems. Mechanistic studies elucidated the coordination environments around the Fe^II and Bi^III centers and the effect of additives on the chiral catalysis. Notably, both Brønsted acids and bases worked as efficient additives in the Fe^II-catalyzed reactions. The assumed catalytic cycle and transition states indicated important roles of water in these efficient asymmetric Mukaiyama aldol reactions in aqueous media with the broadly applicable and versatile catalytic systems.

We describe herein a highly elegant and suitable synthesis of amide products from alcohols and amines through a tandem oxidation process that uses molecular oxygen as a terminal oxidant. Carbon-black-stabilized polymer-incarcerated gold (PICB-Au) or gold/cobalt (PICB-Au/Co) nanoparticles were employed as an efficient heterogeneous catalyst depending on alcohol reactivity and generated only water as the major co-product of the reaction. A wide scope of substrate applicability was shown with 42 examples. The catalysts could be recovered and reused without loss of activity by using a simple operation.

Zn(OH)₂-catalyzed allylation reactions of aldehydes with allylboronates in aqueous media have been developed. In contrast to conventional allylboration reactions of aldehydes in organic solvents, the α-addition products were obtained exclusively. A catalytic cycle in which the allylzinc species was generated through a B-to-Zn exchange process is proposed and kinetic studies were performed. The key intermediate, an allylzinc species, was detected by HRMS (ESI) analysis and by online continuous MS (ESI) analysis. This analysis revealed that, in aqueous media, the allylzinc species competitively reacted with the aldehydes and water. An investigation of the reactivity and selectivity of the allylzinc species by using several typical allylboronates (6a, 6b, 6c, 6d) clarified several important roles of water in this allylation reaction. The allylation reactions of aldehydes with allylboronic acid 2,2-dimethyl-1,3-propanediol esters proceeded smoothly in the presence of catalytic amounts of Zn(OH)₂ and achiral ligand 4d in aqueous media to afford the corresponding syn-adducts in high yields with high diastereoselectivities. In all cases, the α-addition products were obtained and a wide substrate scope was tolerated. Furthermore, this reaction was applied to asymmetric catalysis by using chiral ligand 9. Based on the X-ray structure of the Zn-9 complex, several nonsymmetrical chiral ligands were also found to be effective. This reaction was further applied to catalytic asymmetric alkylallylation, chloroallylation, and alkoxyallylation processes and the synthetic utility of these reactions has been demonstrated.

In this paper, new possibilities for metal amides are described. Although typical metal amides are recognized as strong stoichiometric bases for deprotonation of inert or less acidic hydrogen atoms, transition-metal amides, namely silver and copper amides, show interesting abilities as one of the simplest acid/base catalysts in stereoselective carbon–carbon bond-forming reactions.

A cooperative catalytic system of heterogeneous polymer-supported bi-metallic platinum/iridium (Pt/Ir) alloyed nanoclusters and 5,5′,6,6′-tetrahydroxy-3,3,3′,3′-tetramethyl-1,1′-spiro-bisindane (TTSBI) enabled the facile preparation of quinazoline derivatives with low catalyst loadings and broad substrate scope under mild aerobic oxidative conditions. The ability to perform the reaction in gram-scale and under open-air conditions highlights the synthetic application of this cooperative catalytic system.

Platinum nanoclusters supported on a polymer/carbon black composite material was found to be an excellent catalyst for the oxidative cyclization of phenolic and thiophenolic Schiff bases to 2-substituted benzoxazoles and benzothiazoles under ambient conditions.

Substitution reactions of acetals with carbon nucleophiles are fundamental and conventional organic reactions. We succeeded in the preparation of an optically active acetal, which reacted with a silyl enol ether smoothly to afford the desired adducts in racemic forms. By comparison of the ees of the products with the ees of the recovered acetals, we concluded that the aldol-type reactions proceeded not via direct displacement (S_N2) or contact ion pairs (intimate ion pair) (S_N1) but by a free oxocarbenium ion (S_N1) mechanism. Next, a study to achieve asymmetric catalysis of the acetal substitution reactions was conducted. After many trials, it was found that a chiral niobium complex prepared from pentamethoxyniobium [Nb(OMe)₅] and a tetradentate BINOL derivative could achieve high enantioselectivities. Asymmetric aldol-type reactions of acetals with silyl enol ethers proceeded smoothly to afford the corresponding aldol-type adducts in good yields with high enantioselectivities.

We have recently uncovered a general indium(I)-catalyzed method for allylations and propargylation of acetals and ketals with a water- and air-stable allyl boronate. By using a more reactive allyl borane, we have successfully extended this methodology to the more challenging CC coupling with ethers. Herein, we report an improved methodology for the indium(I)-catalyzed allylation of acetals and ethers, through combination of the allyl boronate with a commercially available “hard” Lewis acid, B-methoxy-9-BBN (BBN=borabicyclo[3.3.1]nonane), as an effective co-catalyst. Significantly, our work highlights for the first time the correlation between the Lewis acidity of “electrophilic” boron-based compounds and their “nucleophilic” reactivity in Csp³–Csp³ couplings, catalyzed by a “soft” low-oxidation main group metal. In addition, we also report several applications of these methodologies to the selective synthesis of various carbohydrate derivatives.

Asymmetric [3+2] cycloaddition of α-aminoester Schiff bases with substituted olefins is one of the most efficient methods for the preparation of chiral pyrrolidine derivatives in optically pure form. In spite of its potential utility, applicable substrates for this method have been limited to Schiff bases that bear relatively acidic α-hydrogen atoms. Here we report a chiral silver amide complex for asymmetric [3+2] cycloaddition reactions. A silver complex prepared from silver bis(trimethylsilyl)amide (AgHMDS) and (R)-DTBM-SEGPHOS worked well in asymmetric [3+2] cycloaddition reactions of α-aminoester Schiff bases with several olefins to afford the corresponding pyrrolidine derivatives in high yields with remarkable exo- and enantioselectivities. Furthermore, α-aminophosphonate Schiff bases, which have less acidic α-hydrogen atoms, also reacted with olefins with high exo- and enantioselectivities. The stereoselectivities of the [3+2] cycloadditions with maleate and fumarate suggested that the reaction proceeded by means of a concerted mechanism. An NMR spectroscopic study indicated that complexation of AgHMDS with the bisphosphine ligand was not complete, and that free AgHMDS, which did not show any significant catalytic activity, existed in the catalyst solution. This means that significant ligand acceleration occurred in the current reaction system.

Aerobic oxidation of aldehydes to 1,2- and 1,3-diol monoesters was catalyzed by polymer-incarcerated gold nanoclusters under ambient conditions. The esterification proceeded much faster with 1,2- and 1,3-diols and their derivatives rather than with methanol.

The unprecedented use of a soluble organoindium species, indium(III) hexamethyldisilazide [In(III)(hmds)₃], for catalytic carboncarbon bond formations between ketones and boronates, is reported. Various functionalized tertiary homoallyl alcohols were generated easily in high yields. Remarkably, free hydroxy and primary amine functionalities proved to be tolerated. A rate acceleration and markedly improved diastereoselectivities were observed in the presence of methanol. Based on preliminary NMR experiments and the α-selectivity with an α-substituted boronate, we assume the in situ generation of reactive allylindium(III) species through catalytic boron-to-indium transmetalation.

Polymer-incarcerated metal(0) nanocluster catalysts were developed based on two techniques: microencapsulation and cross-linking. Pd, Au, Pt, and bimetallic nanoclusters could be efficiently immobilized on polymers containing benzene rings keeping subnanometer- to nanometer-size clusters. Catalysts could be used for redox reactions using molecular hydrogen and oxygen, and could be reused without aggregation of nanoclusters and leaching of metals. Modification of polymers and addition of second inorganic supports sometimes increased their reactivity. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 10: 271–290; 2010: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.201000026

A titanium-based chiral Lewis acid was found to be effective for the ring-opening reactions of meso-aziridines with aniline nucleophiles. The products were generally isolated in high yields and with high to excellent enantioselectivity. The catalytic system was studied by X-ray single crystal analysis. In experiments on non-linear effects a strong non-linear effect of the catalyst system was observed.

We have uncovered Pd⁰-catalyzed intermolecular nonsymmetrical Suzuki–Miyaura-type sp³–sp³ C–C bond formations between allyl carbonates and nontoxic allyl, allenyl, or propargyl boronates. This report represents the first use of these types of boronic esters in this particular context. The present transformations proceeded with high selectivity under remarkably mild conditions, and various functional groups including an aldehyde function proved to be compatible. In addition, several boronates were found to display very unusual reactivity patterns; the higher reactivity of boron as apposed to silicon was clearly demonstrated as well. Finally, the inherent problem of β-hydride elimination associated with intermediary allyl–Pd species was addressed by employing a commercially available Ni⁰ catalyst.

We describe here carbanion reactions using catalytic amounts of bases. The carbanions formed are different from conventional carbanions in which stoichiometric amounts of bases are needed for the formation. Two types of reactions using such carbanions from amide (imido) and ester equivalents are discussed.

Niobium-based chiral Lewis acid was found to be highly effective catalyst for aza-Diels–Alder reactions of imines with Danishefsky‘s dienes. The reactions proceed in high yield with high enantioselectivity for both aromatic and aliphatic imines. The developed methodology was applied to total synthesis of (+)-anabasine.

Polymer-incarcerated, carbon-stabilized gold nanoclusters were found to be highly active in heterogeneous catalysis for the oxidation of secondary alcohols using molecular oxygen in aqueous medium. After optimization of catalyst preparation methods, highly loaded and highly effective catalysts were obtained, and a broad range of secondary alcohols could be oxidized by using these catalysts under mild conditions. The catalysts could be recovered and reused several times without significant loss of activity. Moreover, kinetics of the oxidation reaction with (±)-1-phenylethanol was investigated.

One of the most significant organic transformations in catalyst technology is the selective oxidation of alcohols. The acceleration of catalyst discovery in this field contributes to the economic and environmental impact in the production of useful materials. Heterogeneous catalysts combined with environmentally benign oxidants, such as molecular oxygen and hydrogen peroxide, are major challenges of exploratory research in the oxidation of alcohols. A wide range of recoverable catalysts has now emerged for these oxidation reactions. In this Focus Review, we present an overview of recent developments in immobilized metal catalysts and evaluate the potential of transition metals in the heterogeneously catalyzed oxidation of alcohols.

A novel organic–inorganic hybrid ruthenium (HB Ru) catalyst for the oxidation of alcohols with molecular oxygen has been developed. The catalyst was prepared from a polystyrene-based copolymer, which includes a trimethoxysilyl functionality, and dichlorotris(triphenylphosphine)ruthenium, [RuCl₂(PPh₃)₃], as the metal source. A sol–gel process was employed for heterogenization of the catalyst. The choice of both ruthenium species and trialkoxysilyl-bearing monomers was found to be important for high catalytic activity. In the presence of HB Ru corresponding to 5 mol % loading of ruthenium, the alcohols were oxidized with molecular oxygen or air at atmospheric pressure without any additives to afford the corresponding aldehydes or ketones in good to excellent yields. The catalyst could be recovered and reused at least five times without loss of activity.