Biomedical subjects
Publications and source records attributed to Shu Kobayashi.
Three-component reactions of aldehydes, ammonia, and allylboronates were found to provide homoallylic primary amines in high yields with high chemo- and stereoselectivities. A two-step, one-pot, stereoselective synthesis of an uncommon alpha-amino acid, alloisoleucine, was achieved utilizing this reaction.
[reaction: see text] Suzuki-Miyaura coupling using a highly efficient and reusable polymer-incarcerated palladium (PI Pd) is described. Various coupling reactions proceeded smoothly using PI Pd with phosphine ligands, and the catalyst could be recovered by simple filtration and reused several times without loss of activity.
We have developed highly enantioselelctive reactions of silicon enolates with N-acyl-alpha-iminophosphonates leading to optically active alpha-amino phophonates. A copper (II)-diamine complex was shown to be effective in this reaction, and high levels of yield and selectivity were achieved. It is noteworthy that this reaction opens a way to various biologically important, optically active alpha-amino phosphonate derivatives.
We have developed an efficient system for triphase reactions using a microchannel reactor. Using this system, we conducted hydrogenation reactions that proceeded smoothly to afford the desired products quantitatively within 2 minutes for a variety of substrates. The system could also be applied to deprotection reactions. We could achieve an effective interaction between hydrogen, substrates, and a palladium catalyst using extremely large interfacial areas and the short path required for molecular diffusion in the very narrow channel space. This concept could be extended to other multiphase reactions that use gas-phase reagents such as oxygen and carbon dioxide.
A new type of immobilized palladium, PI (polymer incarcerated) Pd (2b), from Pd(PPh(3))(4) and copolymer (1b) has been developed. The excellent activity of PI Pd has been demonstrated in hydrogenation of various olefins, benzyl ethers, and nitro and aromatic compounds. PI Pd is tolerant under high pressure and high temperature and can be recovered and reused several times without loss of activity even under harsh conditions. Moreover, PI Pd is highly resistant to poisoning by sulfur.
For the synthesis of optically active compounds, chiral catalysts have attracted much attention because large quantities of optically active molecules can be prepared from a small amount of a chiral source. However, many chiral catalysts are often unstable in air (oxygen) and/or in the presence of water. This is especially the case in chiral Lewis acid catalysis, because most Lewis acids are air- and moisture-sensitive. Therefore, many catalysts are prepared in situ in an appropriate solvent just before use, and they cannot be stored for extended periods. We have developed air-stable, storable, and highly efficient chiral zirconium Lewis acids. The catalysts promoted asymmetric Mannich-type, aza Diels-Alder, aldol, and hetero Diels-Alder reactions efficiently with high enantioselectivities. A key to stabilizing the catalysts is an appropriate combination of chiral zirconium Lewis acids with molecular sieves, and the zirconium-molecular sieves-combined catalysts can be stored for extended periods in air at room temperature without loss of activity. Moreover, it has been demonstrated that the catalysts can be recovered and reused.
Asymmetric aldol reactions of ketene silyl acetals with aldehydes using an air-stable, storable chiral zirconium catalyst, which could be stored for at least 13 weeks at room temperature, proceeded smoothly to afford the desired adducts in high yields with high selectivity.
A hydrophobic, low-loading and alkylated polystyrene-supported sulfonic acid (LL-ALPS-SO3H) has been developed for several organic reactions such as the hydrolysis of thioesters, the deprotection of acetals and an acetonide, and the hydration of an epoxide and an alkyne in pure water on the basis of remarkable effects of both the polymer structures and loading levels of the sulfonic acid catalysts.
Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex; the presence of the ligand plays an important role for the catalytic activity; the catalyst was easily recovered and reused without loss of activity.
Two- or three-component aza Diels-Alder reactions of Danishefsky's diene with imines or aldehydes and amines in water took place smoothly under neutral conditions in the presence of a catalytic amount of an alkaline salt such as sodium triflate to afford dihydro-4-pyridones in high yields.
Immobilized catalysts have been reinvestigated from two aspects; as keys to environmentally benign chemical processes and high-throughput organic synthesis for combinatorial chemistry. While most known polymer-supported catalysts are less active than the corresponding original catalysts, new types of polymer-supported catalysts, microencapsulated catalysts, have been developed. The catalysts were immobilized on to polymers using physical envelopment by polymer backbones and interaction between pi electrons of benzene rings of the polystyrenes used as polymer backbones and vacant orbitals of the catalysts. Microencapsulated Sc, Os, Pd and Ru catalysts have been successfully prepared and high activities have been attained. In all cases, no leaching of the catalysts occurred, and the immobilized catalysts were recovered quantitatively by simple filtration and reused without loss of activity. It is noted that this method enables direct immobilization of metals onto polymers, and that normally unstable species such as Pd(0)(PPh3) can be kept stable by this immobilization technique. It is expected that other metal catalysts can be immobilized using this microencapsulation technique.
New types of Lewis acids as water-compatible catalysts have been developed. Various metal salts were found to work as Lewis acid catalysts in aqueous media, and catalytic asymmetric aldol reactions in such media have been attained. Furthermore, Lewis acid-surfactant combined catalysts, which can be used for reactions in water without using any organic cosolvents, have been also developed. These investigations will contribute to reducing the use of harmful organic solvents and to develop efficient catalytic systems which cannot be realized in conventional organic solvents.