Direct functionalization of organic molecules through transition-metal-catalyzed C-H activation enables the straightforward creation of molecular complexity. For these reactions to be useful, the catalyst must efficiently and chemoselectively cleave the inert C-H bond, and also differentiate between the various C-H bonds in an organic molecule. To achieve these requirements, modification of the substrate has been the most popular strategy: the introduction of directing groups, large substituents, or heteroatoms to induce an electronic or steric bias and control reactivity, and more importantly, selectivity. However, these strategies are dependent on the substrate, and therefore not generally applicable. We have started a program aimed at the development of catalysts that can recognize a substrate through noncovalent interactions to control reactivity and selectivity. Thus, we developed a terpyridine ligand that undergoes rollover cyclometallation to create an N,N,C-iridium complex that can selectively borylate the C-H bond adjacent to a fluorine atom in fluoroarene. We also developed spirobipyridine ligands, which possess a fluorene moiety placed perpendicular to the bipyridine plane, allowing molecular recognition groups to be placed at a remote position from the reaction center, thus minimizing repulsive interactions. A spirobipyridine ligand bearing a “steric roof” moiety recognizes a substrate molecule through remote steric interactions to enable meta-selective iridium-catalyzed borylation of monosubstituted arenes. We also found that a spirobipyridine ligand accelerates iridium-catalyzed borylation of arenes through an attractive CH-π interaction between the C-H bond of the ligand and the π electrons of the substrate.

Decarboxylative functionalization of carboxylic acids is an attractive synthetic transformation because carboxylic acid is a fundamental and easily available functional group. Recently, a number of excellent methods for catalytic decarboxylative functionalizations of aliphatic and aromatic carboxylic acids have been reported with transition metal catalysts. However, many challenges still remain in decarboxylative functionalization, such as developing the reaction under metal-free conditions, reactions with tertiary carboxylic acids, and catalytic enantioselective reactions. β-Oxoacids are known to undergo decarboxylation under mild reaction conditions. In the last few years, our research group have studied on the development of novel decarboxylative functionalizations of β-oxoacids and their analogues, especially focusing on reactions with tertiary carboxylic acids under organocatalytic or catalyst free conditions. This article describes our recent research progress on the decarboxylative functionalization of aliphatic carboxylic acids.

1,4-Benzodiazepines, which are important core structures found in hypnotic and anxiolytic drugs, exhibit latent axial chirality. This article describes this axial chirality based on the sp²-sp² axis arising from the Ar-NC(＝O) axis (axis 1) and the Ar-C(＝N) axis (axis 2). The dynamic axial chirality of this scaffold is considered a key core structure contributing to biological activity.

Pioneering research on the axial chirality of pyrimido[1,2-a][1,4]benzodiazepines, in which the conformation of the seven-membered ring is frozen by introducing steric hindrance around axis 1, prompted us to investigate the atropisomeric properties of 1,4-diazepin-2-ones, as represented by diazepam. 1,4-Benzodiazepin-2-ones bearing methyl groups at the C9 position exist only as pairs of enantiomers [(a¹R, a²S) and (a¹S, a²R)]. Similarly, triazolobenzodiazepines bearing methyl groups at C1 and C10 were isolated as the [(a¹R, a²S) and (a¹S, a²R)] isomers. The same results were obtained for 9-methyl substituted quazepam, which contains a thioamide instead of an amide. The results of this study revealed that the two axes (1 and 2) moved together in these flexible benzo-fused seven-membered rings. Examination of the affinity of the GABA_A receptors revealed that each (a¹R, a²S) isomer of these molecules possessed higher activity than its antipode (a¹S, a²R) isomer. This study suggests that 1,4-benzodiazepines with latent axial chirality bind to GABA_A receptors in the (a¹R, a²S) form due to their rapid conformational changes.

This paper describes the development of novel “benzyne platform” molecules and their applications in discovering unique intramolecular reactions. Two types of benzyne precursors for silicon tethering were designed to facilitate the assembly of various arynophiles through Si-O bond formation. Using these platforms, we discovered three intramolecular reactions: (1) (4＋2) cycloaddition with phenolates to construct benzovalerene scaffolds, (2) ene reaction with propargyl amides to synthesize allenes and allenamides, and (3) (3＋2) cycloaddition with ynamides to form indoles. The molecular design effectively suppressed undesired side reactions commonly observed in corresponding intermolecular reactions, enabling the discovery of unique reactivities and selectivities specific to intramolecular settings.

Supramolecular polymers are molecular assemblies in which molecules are regularly arranged in one or two dimensions via non-covalent bonds. Supramolecular polymerization has attracted the interest of many researchers as an important technology for the bottom-up construction of nanomaterials. Regarding material applications, the reversibility of assembly and dissociation is expected to lead to self-healing and stimulus-responsive materials. In addition, as various functional groups can be attached to their interfaces, supramolecular polymers can be used as scaffold materials for cell culture in regenerative medicine and photocatalytic reactions. This review focuses on recent research addressing interfaces of supramolecular polymers. We discuss the design of interfaces of supramolecular polymers and the construction of higher-order structures. Additionally, we cover biomaterials, optoelectronic materials, and hybrid materials that utilize functionalized interfaces on supramolecular polymers.

Azabicyclo[3.1.1]heptanes are recognized as bioisosteres of the meta-substituted pyridine scaffold, as their bridgehead substitution mimics the arrangement of substituents on the meta-substituted pyridine. However, the synthesis of azabicyclo[3.1.1]heptanes remains underdeveloped. This mini-review highlights recent advances in their synthesis through strain-release cycloadditions of bicyclo[1.1.0]butanes.