Nanoporous metal skeleton catalysts are becoming increasingly important in the field of green and sustainable chemistry, due to their high catalytic activities and selectivities together with their robust characteristics. Nanoporous metals (MNPores) are fabricated through chemical or electrochemical corrosive dealloying of monolithic alloys, which produces various MNPores with open network nanoporous structures. The large surface-to-volume ratio compared to bulk metals, together with high density of steps and kinks on ligaments make them promising heterogeneous catalysts having highly active and selective characteristics for molecular transformations. We have developed a variety of heterogeneous catalytic reactions using MNPores primarily under liquid-phase (or liquid-gas phase) conditions. Oxidation of C-OH with O₂ and Si-H with H₂O gives C＝O and Si-OH bond, respectively. Selective reduction of C＝C, C≡C, C＝N, C≡N, and C＝O bonds proceeds smoothly with MNPores, whose selectivities are not easily attainable through previously known catalysts. Cross-dehydrogenative coupling, diboration, C-C bond cross-coupling reaction, azide-alkyne click reaction, and hydrosilylation can be catalyzed selectively and efficiently with MNPores.

Owing to their extremely high bond dissociation energies, carbon-fluorine bonds find limited usage in synthetic organic chemistry. In this context, we investigated novel catalytic carbon-carbon bond forming reactions using alkyl fluorides as electrophiles. As a strategy for realizing the carbon-fluorine bond cleavage, we focused on ate complexes consisting of a highly nucleophilic transition metal anion and a Lewis acidic counter cation. The carbon-fluorine bond in alkyl fluorides is activated by the coordination of fluorine atom to the counter cation, enabling nucleophilic attack from anionic transition metal center or its own ligand. This novel methodology of catalytic conversion of carbon-fluorine bonds to carbon-carbon fragments provides a new synthetic strategy complimentary to traditional transformations.

2,3,6-Trisubstituted pyridine is attractive in drug discovery since a wide variety of medicines and biologically active compounds include the scaffold. Therefore, the development of a facile methodology for synthesizing 2,3,6-trisubstituted pyridines contributes not only to easy preparation of drug candidates but to design of an original scaffold in medicinal chemistry. 3-Substituted-2,6-difluoropyridines play an important role in the synthesis of 2,3,6-trisubstituted pyridines because they have two distinguishable carbon-fluorine bonds susceptible to a tandem nucleophilic aromatic substitutions (S_NAr). Herein, this article describes facile preparation of 3-substituted-2,6-difluoropyridines derived from 3-substituted-2,6-dichloropyridines by using cesium fluoride (CsF) and dimethyl sulfoxide (DMSO) and its application to the synthesis of 2,3,6-trisubstituted pyridines for potent and novel Protein Kinase C theta (PKCθ) inhibitors. Studying on the Structure-Activity Relationship (SAR) of 2,3-dihydroquinazolin-4(1H)-ones, PKCθ inhibitors, identified that filling the lipophilic region with a suitable lipophilic substituent boosted PKCθ inhibitory activity. Strong PKCθ inhibition was observed with 2,3,6-trisubstituted pyridines having lipophilic substituents. The report presents an easier method for preparing 2,3,6-trisubstituted pyridines and practical application to drug discovery.

Chemical protein synthesis (CPS) that consists of solid-phase peptide synthesis and peptide ligation generates not only naturally-occurring proteins with/without posttranslational modifications (PTMs), but also a variety of artificial proteins including unnatural amino-acids such as ᴅ-amino acids and fluorophore-labeled amino acids. This unique property offers new analytical methods for protein structure and interaction in terms of PTMs. In fact, we have chemically synthesized histone proteins with PTMs, which play an important role in regulation of gene expression in eukaryotic cells, and analyzed the effects of PTMs such as methylation, acetylation, and phosphorylation. However, current CPS is still in developing process and includes several issues to be solved such as difficult handling in hydrophobic protein synthesis and time-consuming multistep process for large protein synthesis. We have approached these issues by creating new strategies for peptide ligation. One-pot ligation of five peptide segments was demonstrated for the first time by utilizing multifunctionality of thiophenol compound in deprotection of allyloxycarbonyl group by palladium complex. New thioester precursors for native chemical ligation, which have potential to offer a novel two-way one-pot ligation, have also been developed recently. Furthermore, we have been developing a new strategy for simultaneous ligation of multiple peptides on DNA scaffold, which can connect peptides in highly diluted condition. This article also describes the background and current situation of CPS with our future perspectives.

Antiaromaticity of bond-alternated planar cyclooctatetraene (COT) was predicted to be substantially high based on nucleus-independent chemical shift (NICS), while its destabilization effect was shown to be negligibly small in contrast to the expected character for antiaromatic compounds. The planar structure of typical COT ring is the transition state in the ring inversion process and hence hardly accessible by spectroscopic means. Thus, several molecules with planarized COT cores have been designed and synthesized to investigate the antiaromaticity. By comparing their NICS values, planar COT cores constrained with less aromatic and less strained frameworks were shown to have higher antiaromaticity. To further experimentally compare the antiaromaticity of COT with higher 4n π-systems, a method to evaluate relative hardness of 4n π-systems (n≥2) as a new experimental measure of antiaromaticity was developed. Based on the relative hardness, the high antiaromaticity of planar COT core constrained with one dithieno［3,4-b：3’,4’-d］thiophene unit was confirmed. Furthermore, the retention of high antiaromaticity of planar COT constrained with two dithieno［3,4-b：3’,4’-d］thiophene units after peracid oxidation was also experimentally proved, which is in sharp contrast with the general notion that antiaromatic compounds are unstable. The antiaromatic planar COT core caused narrowing of HOMO-LUMO gap and this feature was successfully applied to ambipolar semiconductor for field-effect transistor.

Recently, the development of optically active luminophores that can emit circularly polarized luminescence (CPL) with high functionalities, such as a high dissymmetry factor (g_CPL) and a high quantum yield (Φ_F), has attracted attention in the field of chiroptical organic materials. However, the design of chiral luminophores that bear CPL tuning, switching, memory, and elimination has been hampered by the fact that the relationship between the structure of the photoexcited state and the chirality of the photoexcited state of chiral luminophores is not yet fully understood.

Typically, a pair of enantiomeric organic fluorophores is indispensable for the emission of opposite CPL. Unfortunately, it is not always easy to prepare both enantiomers. Hence, it is necessary to find an alternative, non-classical route for controlling the sign of CPL in chiral fluorophores without the use of a fluorophore that has opposite chirality. In this paper, we report a non-classical approach for controlling the sign, wavelength, and intensity of the CPL. We report that in binaphthyl-derived fluorophores having the same axial chirality, the CPL sign can be controlled by 1) altering the dihedral angle of the axially chiral binaphthyl units, 2) tuning the linkers between the binaphthyl and fluorescent units, 3) selecting the bonding position of the fluorescent unit, 4) taking advantage of the neighboring effect between the fluorescent units, and 5) selecting appropriate organic host matrices. These non-classical methods may be useful for the development of novel chiral organic fluorophores, particularly when one of the enantiomers is easily accessible in nature. This non-classical approach to control the sign of CPL is instrumental for the development of novel chiral fluorescent systems.

Metal fluorides such as KF and CsF are inexpensive and easy-to-handle nucleophilic fluorinating reagents while their insolubility in most organic solvents often causes a problem in their synthetic use. In this review, examples of nucleophilic fluorination promoted by a hydrogen-bonding donor are described. Moreover, a recent research on asymmetric nucleophilic fluorination using a chiral hydrogen-bond donor catalyst is introduced.