Shū Kobayashi

Recent advances in immobilized metal catalysts for environmentally benign oxidation of alcohols.

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.

Michael reactions in water using Lewis acid–surfactant-combined catalysts

Abstract Michael reactions in water using Lewis acid–surfactant-combined catalysts (LASCs) have been developed. In the presence of a catalytic amount of scandium tris(dodecyl sulfate) (STDS), reactions of various β-ketoesters with enones proceeded smoothly in water without any organic solvents, to afford the corresponding Michael adducts in high yields. The catalytic activity in water was found to be higher than that in organic solvents. Among the Lewis acids tested, STDS was proved to be the most superior Lewis acid catalyst for Michael reactions in water.

A Gold-Immobilized Microchannel Flow Reactor for Oxidation of Alcohols with Molecular Oxygen†

Golden capillaries: A gold-immobilized capillary column reactor allows oxidation of alcohols to carbonyl compounds using molecular oxygen. These capillary columns (see picture) can be used for at least four days without loss of activity.

Lewis Acid Catalysis in Water with a Hydrophilic Substrate: Scandium‐Catalyzed Hydroxymethylation with Aqueous Formaldehyde in Water

The use of Lewis acids as catalysts is one of the most powerful strategies in organic chemistry. In general, conventional Lewis acids such as AlCl3, TiCl4, BF3·OEt2, SnCl4, etc., require strictly anhydrous conditions because they immediately react with water in preference to the substrates, resulting in serious decomposition of the catalysts or the substrates. To address this issue, water-compatible Lewis acid catalyzed organic reactions have been intensively studied in the past decade. Considering the growing concern over environmental pollution, water is an ever more desirable alternative to organic solvents, as water is a clean, safe, and inexpensive solvent. Several surfactant-type catalysts derived from water-compatible Lewis acids have been developed, and catalytic asymmetric reactions have been achieved in water without requiring any organic cosolvents. These reactions proceeded smoothly by creating hydrophobic domains in the water to stabilize and concentrate the organic substrates, or by suppressing undesired reaction pathways that may occur in water. One of the key factors for these successes is the hydrophobicity of the substrates. Aqueous formaldehyde solutions (i.e. formalin) are one of the most important single carbon electrophiles and are representative of a hydrophilic substrate. As mentioned above, the hydrophobicity of the substrates is very important for organic reactions in water and hydrophilic substrates are often difficult to handle in water. Herein, we address this issue and describe a catalytic hydroxymethylation reaction with aqueous formaldehyde in which water is the sole solvent. First, we carried out the hydroxymethylation of silicon enolate 1 with 1 equivalent of formaldehyde (36% aqueous solution; aq. HCHO) in the presence of 2 mol% of scandium tris(dodecyl sulfate) (Sc(DS)3) [4] at a 1.0m concentration at 20 8C for 1 hour in water. The reaction proceeded sluggishly and afforded desired product 2 in poor yield. Increasing the amount of aq. HCHO to 3 equivalents improved the yield to 25%, but addition of more aq. HCHO did not result in increased amounts of the desired product (Figure 1a, navy blue). Gratifyingly, while optimizing the reaction conditions, we found that desired product 2 was obtained in 82% yield by using 5 equivalents of aq. HCHO and by extending the reaction time to 8 hours. Notably, under these conditions the competitive hydrolysis of silicon enolate 1 was observed. The loading levels of the catalyst also has an effect on the yield; the yield of 2 showed good correlations to the amount of Sc(DS)3 used, which ranged from 2, 5, 10, to 20 mol%. To improve the yield, we also investigated the concentration effect of aq. HCHO for each of the different Sc(DS)3 loadings (2, 5, 10, or 20 mol%) in the presence of 5 equivalents of aq. HCHO (Figure 1b). In the presence of 10 and 20 mol% of Sc(DS)3, the yields were improved to more than 80% as the concentrations increased to 2.0m, however, no additional improvement was observed when the concentration was increased to more than 2.0m. In the cases of 2 and 5 mol% of Sc(DS)3, the yields leveled off at much lower concentrations of 0.5m and 1.0m, respectively. These results indicated that Sc(DS)3 might be saturated by aq. HCHO. On the basis of the experiments described above, it can be said that despite the good solubility of HCHO in water, the amount of HCHO in the hydrophobic environment increases in the presence of Sc(DS)3 because of Lewis acid–Lewis base interactions between Sc(DS)3 and HCHO, therefore, allowing the reaction of HCHOwith silicon enolate 1 to proceed smoothly in water. After tuning the reaction conditions, we found that several silicon enolates reacted with aq. HCHO (5.0 equiv) in the presence of 5 mol% of Sc(DS)3 in water (1.0m) at 20 8C Figure 1. Hydroxymethylation of 1. a) Changes in yield as a function of the number of equivalents of HCHO at different catalyst loadings for a 1.0m solution monitored over 1 hour. b) Changes in yield as a function of concentration at different catalyst loadings for reaction containing 5.0 equivalents of HCHO monitored over 8 hours.

Chiral Scandium-Catalyzed Enantioselective Hydroxymethylation of Ketones in Water

ric hydroxymethylation of silicon enolates in water (Scheme 1). In this reaction, readily available and inexpensive aqueous formaldehyde (formalin) could be successfully employed. Although this asymmetric hydroxymethylation is simple and shows high enantioselectivities for a variety of silicon enolates, direct use of ketones instead of silicon enolates seems to be attractive from an atom economy point of view. Recently, C rdova and Yamamoto have reported organocatalytic asymmetric hydroxymethylation using formalin. Although high enantioselectivities were observed in their systems, chemical yields were moderate and substrates are relatively limited. Therefore, efficient and general asymmetric hydroxymethylation is desirable. We started to investigate asymmetric hydroxymethylation of ketones in water, and in this report, preliminary results using chiral scandium catalysts are described. At the outset, several reaction conditions were examined for the scandium-catalyzed asymmetric reaction of a-methylindanone (3 a) with formalin in water using chiral N-oxide 1 a as a ligand (Table 1). Although the reaction proceeded

Immobilization of Ruthenium in Organic–Inorganic Hybrid Copolymers: A Reusable Heterogeneous Catalyst for Oxidation of Alcohols with Molecular Oxygen

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.

Nazarov‐type Reactions in Water

Different in water! We have developed Nazarov-type reactions in water. Different reaction courses compared with those in organic solvents are observed in water. In the presence of a scandium based, surfactant-type catalyst, water-trapping products are obtained exclusively. The results presented are unprecedented and provide a valuable extension to information available regarding organic reactions in water.

Chiral Zirconium Complex as Brønsted Base Catalyst in Asymmetric Direct-type Mannich Reactions

Development of efficient methods for preparation of optically active amino acids is one of the most important topics in synthetic organic chemistry. Asymmetric Mannich-type reactions have been recognized as one of the most efficient methods to provide optically active b-amino esters, because new carbon–carbon bond formation and chiral induction are achieved at the same time in a single reaction step. Recently, several types of catalytic asymmetric Mannich-type reactions have been reported; among them, direct-type Mannich reactions are the most attractive from an atom economical point of view, because no stoichiometric amounts of bases or metals for pre-activation of carbonyl donors are required. In previous papers, our group has reported asymmetric Mannich-type reactions using chiral zirconium Lewis acid catalysts prepared from zirconium alkoxides and BINOL derivatives. The zirconium catalysts could interact with imines and their equivalents to create excellent asymmetric environments, realizing high enantioselection. On the other hand, some zirconium catalysts possess alkoxide parts on their structure, suggesting that such catalysts could potentially work as Brønsted bases. While it was already disclosed that zirconium alkoxides worked as Brønsted bases in direct-type aldol reactions, few successful examples of catalytic asymmetric direct-type reactions using chiral zirconium catalysts as Brønsted bases were reported. Herein, we describe a successful example of catalytic asymmetric, directtype Mannich reactions using a chiral zirconium catalyst as Brønsted base. We selected the Mannich-type reaction of malonate with a-iminoester as a model, providing an efficient method for preparation of optically active a-amino acid derivatives (Scheme 1). While asymmetric variants of this reaction