We have developed three catalytic reactions involving borylation and C-C bond formation using bis(pinacolato)diboron (B₂pin₂), and have extended their use to the synthesis of pharmaceuticals and luminescent dyes. In addition, we have also elucidated the photophysical properties of those dyes. The first reaction is a Cu-catalyzed stereoselective borylation of glycosyl bromide to β-glycosyl trifluoroborates, which has been further expanded to synthesize aryl β-C-glycosides via Pd-catalyzed stereospecific cross-coupling with aryl bromides. These methods were applied to the stereospecific synthesis of the SGLT2 inhibitor, canagliflozin. The second reaction involves the copper-catalyzed borylation of acyl chlorides to form acyl trifluoroborates, which have further been applied to the synthesis of fluorescent C,N-chelated 2,2-difluoro-1,4-diazaboroles via condensation with various amino-heterocycles. The third reaction is an organocatalytic pinacol coupling of aryl aldehydes using B₂pin₂ as a reductant and a substituted pyridine catalyst. The resulting diols were converted to various substituted benzils, revealing the luminescent properties such as phosphorescence, fluorescence, and self-recovering phosphorescence-to-phosphorescence mechanochromism. These studies demonstrated the usefulness of the developed methods for producing pharmaceuticals, pharmaceutical candidates and novel materials, as well as making possible the investigation of the products physical properties.

Macrocyclic rings and cages were constructed by assembling anthracene units to create novel aromatic compounds. Key building units, 2,7-dibromoanthrcene derivatives, were prepared by classical methods or using an improved method via the Hartwig-Miyaura borylation. Tripodal triptycene units required for the cage structures were prepared by regioselective bromination. Macrocyclization of the anthracene units by the Yamamoto coupling afforded cyclic hexamers having disk-shaped nonplanar frameworks. A hexameric ring without inner substituents formed Saturn-shaped supramolecular host-guest complexes with fullerene guests C₆₀ and C₇₀ via multipoint C—H…π interactions. Cages prepared by coupling reactions also formed stable complexes with the fullerene guests. Some related studies of the anthracene-based rings and cages are introduced. The significance of and perspectives for the chemistry of anthracene rings and cages are reviewed.

Application of the phytosiderophore 2′-deoxymugineic acid (DMA) was found to enable rice growth in alkaline soils, which are unsuitable for agriculture and cover 1/3 of the world’s land. For practical use as a fertilizer for such soils, a cheaper and stable analog, proline-2′-deoxymugineic acid (PDMA), was developed. Application of PDMA ameliorated the iron deficient chlorosis in rice plants on alkaline soils in a pilot field. To drive forward functional studies, molecular probes for mugineic acid (MA) were developed: these enabled the uptake of fluorescently labeled MA into cells to be observed. To supply enough of the probes for in vivo experiments, a streamlined synthetic pathway for the production of plentiful amounts of MA was established.

Computational chemistry is a powerful tool for exploring the unique behavior of organic compounds. We have employed computational techniques to analyze mechanisms of diastereo- and regioselective reactions, which are key transformations in studies on natural product synthesis. Our approach involves ensuring conformational diversity when calculating the transition states of target reactions, allowing us to obtain many geometrically different transition states and systematic information on favorable and unfavorable geometries, which can lead to the identification of origins of the selectivity. In this account, we describe the protocol of a comprehensive search for transition states. The protocol was applied to the mechanistic analyses of the aza-spirocyclization in the total synthesis of fasicularin, the aldol reaction in the synthetic study of amphidinolide L, and the Au-mediated 6-exo-dig ether cyclization in the synthetic study of ent-formosalide A.

Organic compounds that emit phosphorescence at room temperature have attracted many researchers in various fields such as the analytical sciences, bio-imaging/sensing, chemical sensing, data protection technology, and organic light-emitting diodes. Since the lowest triplet excited state of organic luminophores readily undergoes non-radiative decay due to molecular motions occurring at room temperature, the use of precious metals such as iridium and platinum is currently standard for achieving efficient phosphorescence from organic luminophores at room temperature. However, precious metals are limited resources and thus very expensive. Therefore, new approaches to the design and development of precious-metal-free organic phosphors are highly sought after. This article describes our research on this topic. After a brief introduction to phosphorescence, we first present our serendipitous discovery of phosphorescent 1,4-diaroyl-2,5-dibromobenzenes and dual fluorescent-phosphorescent dimethyl 2,5-bis(siloxy)terephthalates. The following sections provide an overview of the molecular design and photoluminescence properties of 2,5-disiloxy-1,4-dibenzoylbenzenes, 1,4-diaroyl-2,5-bis(silylmethoxy)benzenes, 2,5-bis(arylsulfonyl)-1,4-disiloxybenzenes, and 2,5-bis(diarylphosphynyl)-1,4-disiloxybenzenes, which we have developed as precious-metal-free phosphors inspired by our original serendipitous discoveries.

Herein we summarize our recent progress on the design, synthesis, and catalytic application of triarylboranes. We demonstrated that structurally well-characterized triarylboranes catalyzed the hydrogenation of N-heteroaromatics and carbonyl compounds when crude H₂ (a mixture of H₂, CO, CO₂, and CH₄) was directly used as reductant. In addition, we proposed a concept of ‘remote back strain’ to finely tune the Lewis acidity of triarylboranes by regulating the stability of Lewis base-borane adducts via an intramolecular repulsion between the meta-substituents on the aryl groups. Such approaches were eventually combined with machine learning and efficiently assisted the optimization of boranes that catalyzed the reductive alkylation of multiply-substituted aniline derivatives, including amino acids and peptides, using H₂ as reductant. These results manifest a new aspect of main-group catalysis beyond its application as a simple alternative to well-established transition metal-catalyzed processes.

In this era of advanced technologies, is there still wisdom to be gleaned from nature? The answer is an unequivocal “Yes”. Discovering new natural products from nature, determining their structures, and revealing their biological activities - this classical natural product chemistry is still a catalyst for innovation in a wide range of fields, including the expansion of chemical space, elucidation of life phenomena, and drug discovery. In this account, we describe a comprehensive bioorganic study of iezoside (1a), the novel marine natural product we recently discovered, including its discovery, synthesis, mode of action, and structure-activity relationships.

Customized drug delivery systems are essential for precision medicine, with antibody-drug conjugates (ADCs) representing a pivotal approach that integrates cytotoxic payloads with monoclonal antibodies (mAbs) through sophisticated chemical linkers. However, optimizing ADC stability while achieving controlled payload release remains challenging. The FDA-approved valine-citrulline (Val-Cit) linker commonly used in ADCs, suffers from issues such as hydrophobicity-induced aggregation, limited drug-antibody ratio (DAR), and premature payload release.

Due to their efficient production of reactive oxygen species (ROS) under visible light irradiation, fullerenes (C₆₀ and C₇₀) are useful photosensitizers for applications in photodynamic therapy (PDT). To be suitable as medicines, water-soluble fullerene materials were developed by complexation or conjugation with biocompatible polymers such as poly(vinylpyrrolidone) (PVP) and polyethylene glycol (PEG), and their ROS generation abilities were investigated. In addition, a C₆₀-tripod molecule was synthesized for the modification of AFM tips and used for spatially and temporally controlled oxidative damage of DNA origami immobilized on the surface.