Amide bonds are important chemical linkages constituting many natural products and pharmaceuticals. Although the dehydrative condensation of the carboxylic acids with amines is the most straightforward approach to construct amide bonds, the common methods require a stoichiometric amount of coupling reagents, which causes the problems associated with poor atom economy and practical operation. In contrast, the catalytic direct dehydrative amidation is an ideal approaches because water is the only byproduct. After the pioneering report by Yamamoto and Ishihara in 1996, the variety of organoboron-catalyzed dehydrative amidations have been developed for a quarter of a century. This article highlights our recent studies on diboronic acid anhydride (DBAA)-catalyzed dehydrative amidations. DBAA designed on the basis of a recent mechanism has been identified as a powerful catalyst for dehydrative amidations of β- or α-hydroxy carboxylic acids. Under optimized conditions, the dehydrative condensation could be promoted with only 0.01 mol% of catalyst. Another noteworthy feature is that the catalysis did not require any dehydrative operations such as azeotropic reflux with a Dean-Stark apparatus or adding molecular sieves, showing excellent chemoselectivities for β-hydroxy carboxylic acids over simple carboxylic acids. DBAA was also applicable to the catalytic synthesis of β- or α-hydroxy carboxylic acid-derived Weinreb amides and catalytic peptide bond formations of β-hydroxy-α-amino acids. The synthetic utility of the catalysis was demonstrated by the concise synthesis of pharmaceutical, chiral building block, and acyloin natural products.

Development of transition metal complexes and clusters featuring organo group-14 ligands have attracted much attention because they often exhibit unique reactivity as well as chemical properties. Group 14 ligands tend to show strong electron donating property and high trans-influence, this led to the development of highly reactive metal species. In addition, heavier group-14 elements tend to adopt hypercoordinated structures such as five- or six-coordinated structures, thus they could function as the effective supporting ligand to construct the metal clusters consisting of multiple metal atoms. Transition metal compounds bearing group-14 ligands have generally been synthesized by the reactions of appropriate transition metal precursors with group-14 hydrides such as hydrosilanes. On the other hand, it has been known that they could also be accessible by the reaction of metal precursors with organo group-14 compounds bearing E-E (E=Si, Ge, Sn) bond via insertion of the metal species into E-E bonds. The latter reactivity of the E-E bonds gave rise to the idea that organo group 14 compounds, which contain multiple E-E bonds, might serve as templates to assemble multiple metal atoms via sequential insertion of the metal species into these E-E bonds. Based on this hypotheses, we have examined the reactions of a series of organo group 14 compounds having multiple E-E bonds with appropriate low valent late transition metal precursors, and we found that a number of metal clusters and complexes were successfully synthesized in one step with high selectivity. This article describes the synthesis of metal complexes and clusters based on this methodology, and application of the obtained compounds as catalysts will also be enclosed.

The authors have been working on the development of pseudo-glycans (pseudo-glycoconjugates) in which the O-glycosidic linkage of the natural-type glycan structure is replaced by a C-glycosidic linkage. These analogue molecules are not degraded by the glycoside hydrolases expressed in cells, and thus are expected to be useful molecular tools that maintain the original biological activity of carbohydrates at the cell level. However, their biological potentials are not well understood because quite limited number of pseudo-glycans have been synthesized. In this article, the author summarizes our recent report on the creation of C-glycoside analogues of ganglioside GM3. The author has devised the CHF-sialoside linkage to mimic the properties of the O-sialoside bond in the development of pseudo-GM3. Conformational analysis of the synthesized CHF-sialoside disaccharides confirmed that the expected conformational control by F-atom introduction was achieved, and furthermore, results suggesting that this contributed to the enhancement of biological activity were successfully obtained. In order to further validate the usefulness of the C-glycoside analogues, it is important to streamline the cumbersome synthesis process. The author proposed the direct C-glycosylation method using atom-transfer radical coupling, which was utilized to the synthesis of pseudo-isomaltose and pseudo-KRN7000.

Organocatalysis has become widely used since the early 2000s as a third type of catalysis in addition to the two types of catalysis, metals and enzymes, and the Nobel Prize in Chemistry was awarded in 2021 for its pioneering achievements. In organocatalytic reactions, stereoselectivity is often controlled by the cooperative action of weak interactions such as hydrogen bonding and dispersion interactions, and it is extremely difficult to elucidate the stereocontrol mechanism from experimental perspectives. On the other hand, recent advances in computational chemistry have made it possible to deeply understand transition state and clarify important roles in controlling the stereoselectivities in organocatalytic reactions. Furthermore, the findings computationally revealed can provide guidelines for the design of new reactions and catalytic structures. Herein, we describe asymmetric oxidation reactions using conformationally flexible bifunctional guanidine-bisurea organocatalysts developed by us and theoretical analysis of the transition states of these reactions. We also discuss the development of novel catalytic reactions and catalyst designs based on the obtained transition state models.

Since the reproductive behavior of plants depends on the circadian clock, artificially controlling the clock timekeeping system could enable improvement in food production and supply of biomass resources. Despite the importance of posttranslational modification in the circadian clock, those in the plant variant are less explored, likely due to genetic redundancy. As such, the modulation of circadian rhythms by small molecules (circadian clock modulators) without genetic modification has received significant attention in recent years. We successfully identified these circadian clock modulators, PHA 767491 and BML-259, to lengthen the circadian rhythm of Arabidopsis thaliana using our developed high-throughput screening. Herein, we described structure-activity relationship studies of PHA767491 and BML-259 and their mechanisms in plant circadian clocks. The development of higher active molecules and the discovery of target proteins have enabled further mechanistic elucidation of the plant circadian clock.

Quantum mechanical tunneling (QMT) is a quantum mechanical phenomenon that enables particles to penetrate potential energy barrier despite a lack of energy to overcome it. It has become clear that how important tunneling is for understanding the rates and selectivities of chemical reactions in the last few years. In this short review, recent examples of hydrogen tunneling reactions are described.