Hydrogen (H₂) is regarded as a clean energy source due to the production of only H₂O as a by-product by its combustion, and widely utilized as a reductant in organic chemistry. However, the handing of flammable H₂ should be strictly regulated by law and H₂ is industrially produced by the steam forming of CH₄ accompanied with emission of CO₂. Therefore, the development of methodology to generate H₂ in situ without generating CO₂ and the direct use of H₂ is eagerly desired from the viewpoints of green sustainable chemistry. We continuously investigate two types of H₂ generation methods using mechanochemical activation of water, alkanes, etc. and heterogeneous platinum group metal-catalyzed dehydrogenation of alcohols, unsaturated alicyclic hydrocarbon derivatives, etc. Mechanochemical collision and friction energy of stainless steel (alloy of Fe, Cr, and Ni) balls in a planetary ball mill realized the quantitative generation of H₂ from H₂O and in situ-generated H₂ could be directly used as a reductant towards organic compounds bearing reducible functionalities, such as alkenes, alkynes, nitro group, aromatic halides, etc. Meanwhile, the commercially available carbon-supported platinum group metal catalysts (e.g., Pd/C, Rh/C, Ru/C, and Pt/C) were found to catalyze the dehydrogenative oxidation of alcohols in H₂O as a green solvent to generate H₂, which was effectively utilized in the reduction of comparatively stable aromatic fluorides and arene nuclei. Furthermore, in situ-generated H₂ was also adapted as an activator of platinum metal to facilitate the H-D exchange reaction (deuterium-labelling) of various organic compounds. Furthermore, the Pd/C-catalyzed dehydrogenation of unsaturated alicyclic hydrocarbon derivatives has the potential to provide a wide variety of aromatic compounds.

Our concept of natural product synthesis is to directly construct the ring skeletons, frequently occurring in natural products with strong biological activities, from easily accessible linear substrates, and our group has established practical methods for synthesizing useful natural products along our synthetic strategy. First, we developed a cycloisomerization reaction to directly synthesize nitrogen-containing spirocycles from linear substrates, accompanied with construction of a stereogenic tetrasubstituted spiro-carbon. The reaction enabled us to achieve the efficient total synthesis of lepadiformines, revealing a phenomenon of their enantiodivergence. The synthesis of histrionicotoxins, frog poisons, was also accomplished through our original cyclization reaction. In addition, we found the critical switching of cyclization modes of polyepoxides in acidic aqueous media and neutral water, and the novel cascade cyclization was applied to the synthesis of natural products.

Protecting groups (PGs) still occupy an important position in the organic synthesis, despite negative campaign declaring that the use of them is not step-economical. Although an enormous number of PGs have been developed to date, there still are demands of new PGs that can be installed and cleaved at the desired timing and situation. Recently, we have focused on some projects to revisit the usefulness of alkoxymethyl PGs. In this review article, the property of 2-naphthylmethoxymethyl (NAPOM or NOM) and 1-naphthylmethoxymethyl (1-NAPOM, NAPOM^I or NOM^I) groups, our newly developed alkoxymethyl PGs, would first be introduced. Subsequently, application of the alkoxymethyl PGs to peptide- and glyco-chemistry was discussed. In the peptide chemistry, the NAPOM group was introduced on a π-nitrogen of histidine to suppress the racemization during peptide synthesis. On the other hand, in the glycochemistry, alkoxymethyl PGs were installed on a hydroxy group at C2 position, and used for the anchimeric assistance to ensure 1,2-trans selective glycosylation. Furthermore, because 2-O-alkoxymethyl protected donors were found to be more reactive than the conventional 2-O-acyl ones, a one-pot strategy for the synthesis of 1,2-trans oligosaccharides could be developed.

Nonalternant hydrocarbons, which involve odd-membered rings, are an intriguing family for investigations of the structure-property relationship of π-conjugated carbocycles. Bicyclic nonalternant hydrocarbons, azulene, pentalene and heptalene, are the most fundamental molecules in a series of nonalternant hydrocarbons. Over the last 15 years, the chemistry of nonalternant hydrocarbons has experienced a remarkable renaissance mainly thanks to advances in synthetic methodologies. Ring-annulated nonalternant π-systems, in which some benzenoid rings are attached into the nonalternant frameworks, are the key players in their resurgence. The ring annulation impacts the electronic structures of nonalternant subunits, which modulates the HOMO-LUMO gap and creates perturbations in their inherent (anti)aromatic nature. The tunable, narrow HOMO-LUMO gap has offered rich studies into the electronic properties of open-shell characters and into their potential applications as functional organic optoelectronic materials. This article describes our recent studies on the synthesis and characterization of π-extended nonalternant hydrocarbons, containing azulene, pentalene and heptalene frameworks.

The use of flow microreactors shows some advantages such as precise temperature or reaction time control. Particurally, the efficient mixing in flow microreactors often affords the unique reaction results compared to those in the conventional batch reactors, because it can be enhanced the encounter frequency of each reagent in very narrow reaction channel. Of particular, even very unstable intermediates which it is difficult to be existed in batch reactors, can be reacted with coupling partners on highly efficiency in flow microreactors. In this work, three kinds of organic reactions ((1): cross-coupling reaction, (2): nucleophilic aromatic substitution reaction, (3): photocatalytic reduction reaction) were performed using flow microreactors. Every examples show the highly efficiency or highly productivity because of the specific character of flow microreactors compared to that in batch reactor. Especially, unique reactor-dependent result (different product selectivity from the batch reactor) was also observed in photoreaction.

Rotaxanes, which are threading chemical structures between macrocycles and axles, have been widely developed in the field of fundamental and applied chemistry. Numerous examples of the syntheses of rotaxanes using efficient template methodologies have been reported. However, as the number of macrocycles increases, the fine synthesis of [n] rotaxanes, where the number of macrocycles on the axle is precisely defined, remains a challenging target in the field of synthetic supramolecular chemistry. Herein, I review and discuss the recent reports and trends regarding the effective and precise synthetic methodologies for [n] rotaxanes.

The difluoromethyl group attracts growing attention as a chemically stable lipophilic hydrogen bond donor. However, there have been limited experimental attempts to explore the hydrogen bonding nature of the group until recently. In this review, the fundamental properties of the difluoromethyl group elucidated by the recent studies are introduced, as well as applications for functional molecules.