Carbene is a two-coordinate neutral carbon species, characterized by two non-bonding electrons on the carbon atom. By the configuration of non-bonding electrons, singlet carbene can be classified into two types, σ²π⁰ and σ⁰π². While σ²π⁰ carbenes, represented by N-heterocyclic carbene or cyclic alkyl(amino)carbene, have been well-studied, properties of σ⁰π² carbenes have yet to be fully revealed. Diborylcarbene (DBC), wherein two boryl groups are attached to the carbene carbon, has long been theoretically predicted to adopt the σ⁰π² configuration and exhibit highly electrophilic nature. However, to date, no experimental investigation beyond trapping reactions with some Lewis bases has been accomplished. In this situation, we focused on carbenoid, which is often employed as a synthon for carbene in synthetic organic chemistry, for an equivalent to DBC. This article summarizes our recent progress in the investigation of the properties of diborylcarbenoid and DBC.

The development of catalytic asymmetric reactions with high reactivity and stereoselectivity is a central issue in the synthetic organic chemistry. The precise and rational design of catalysts is key to achieving this goal. We have studied catalytic asymmetric hydrogenation and cyanation using our original chiral ruthenium (Ru) complexes. These Ru complexes, each bearing a chiral diphosphine ligand and an amine-based ligand, exhibit excellent catalytic activity and enantioselectivity for the hydrogenation of ketones under neutral to slightly basic conditions. Mechanistic studies suggest that this high catalytic performance is attributed to a six-membered pericyclic-type transition state (metal-ligand cooperative transition state). The chiral environment can be readily tuned by changing the combination of these two ligands. As a result, a wide variety of simple and functionalized ketones were successfully subjected to the asymmetric hydrogenation. Imino compounds and several chiral esters were also smoothly converted to the corresponding amines and primary alcohols, respectively, in a highly stereoselective fashion. The resulting Ru complexes also showed excellent catalytic performance in the enantioselective isomerization of primary allylic alcohols, affording the aldehydes in nearly optically pure form. Combined systems consisting of amino acidate/diphosphine-Ru complexes and lithium compounds acted as effective catalysts for the asymmetric cyanosilylation of various aldehydes and both simple and functionalized ketones. The Ru·Li bimetallic complexes were isolated as crystalline compounds, and these efficiently catalyzed the asymmetric hydrocyanation of aldehydes. These combined catalytic systems were also successfully applied to the asymmetric conjugate cyanation of α,β-unsaturated ketones and acylpyrroles. The Strecker-type reaction of N-alkoxycarbonyl aldimines and α-ketimino esters with the combined catalysts afforded the corresponding aminonitriles in high enantioselectivity. This article provides an overview of the catalyst-design concepts and the catalytic performance achieved in asymmetric hydrogenation and cyanation.

Covalent connection of two different frameworks generates new molecules, displaying unique self-assembled structures and properties. The representative is a linear amphiphile, bearing an alkyl chain and an ionic head, which forms a spherical assembly, so-called micelle, in water. This review describes our recent progress on bent amphiphiles for the development of new functional micelles. On the basis of our previous studies using anthracene and pentamethylbenzene panels, we prepared novel aromatic and cycloalkane micelles in water, by the rational design of bent amphiphiles, providing hetero-aromatic panels (i.e., phenothiazine and carbazole), cycloalkyl groups (i.e., cyclohexane and adamantane), organometallic units (i.e., ferrocene), and chiral frameworks (i.e., terpene and binaphthyl) as the hydrophobic part. Our previous and present micelles exhibited characteristic host functions, through efficient encapsulation of metal-complexes (i.e., M＝Pt, Ni, and PdAu), polyacenes, and axially chiral compounds in water. The micelle structures and properties could be altered by external stimuli with/without guest molecules. In addition, efficient chiroptical induction of achiral organic and metal-complex dyes was demonstrated within the chiral micelles in water.

Chemical synthesis in flow reactors (flow synthesis) has received significant research interest from both academia and industry. Flow synthesis offers several advantages over traditional synthesis in batch reactors. The most important features of flow synthesis include “precise mixing,” “precise temperature control,” and “precise residence time control.” Flash Chemistry is widely recognized as a representative example of flow synthesis, utilizing all three of these elements to achieve “chemical reaction control that cannot be realized with traditional batch synthesis.”

This article demonstrates the application of flow synthesis in the field of process chemistry to establish pharmaceutical manufacturing methods. It also introduces examples of scaling up Flash Chemistry and effectively utilizing flow synthesis technology in the manufacturing processes of active pharmaceutical ingredients (APIs). Additionally, cases where flow synthesis has been used under good manufacturing practice (GMP) control, an important concept in pharmaceutical manufacturing, are presented. Furthermore, examples of integrating electrochemical synthesis (anodic oxidation) with flow synthesis, which is expected to be a future green chemical synthesis method for API manufacturing processes, are described.

Hydrosilylation reactions have long served as a fundamental technology for the production of organosilicon compounds. Platinum-catalyzed hydrosilylation has long been employed in the industrial process. However, the widespread use of platinum catalysts presents two major challenges: Their high cost due to the scarcity of platinum, and their limited ability to achieve highly selective synthesis of high-performance organosilicon materials. Therefore, the need to develop alternative catalysts that are both highly selective and/or environmentally sustainable has become increasingly urgent in the silicone industry. To address these issues, we have developed new hydrosilylation catalysts tailored for specific industrial needs.

Firstly, we focused on designing nickel-based catalysts as precious metal catalyst surrogates. It was revealed that a series of cationic nickel-arene complexes serve as good catalysts for selective hydrosilylation of various olefins under mild conditions. These catalysts outperformed Karstedt’s catalyst in several model reactions and demonstrated applicability even to substrates containing coordinating functional groups, which easily deactivate conventional platinum catalysts.

Next, an efficient hydrosilylation reaction of allyl chloride with trichlorosilane was achieved using the Rh(I) catalyst to selectively form trichloro(3-chloropropyl)silane. Trichloro(3-chloropropyl)silane is industrially synthesized on the order of several thousand tons per year as a key intermediate to access various silane coupling agents. Conventional platinum catalysts suffer from deactivation owing to the occurrence of Tsuji-Trost type side reactions, leading to low reaction selectivity. The catalyst enabled drastically improved efficiency (turnover number, TON, 140,000) and selectivity (>99%) to be achieved compared to conventional Pt catalysts. Furthermore, the system could be scaled up to kilogram-scale synthesis.

Finally, we developed a ruthenium-based catalytic system for the selective hydrosilylation of allyl-terminated poly(ethylene glycol)(PEG) derivatives, which are widely used in biomedical and electronic materials. This led to the synthesis of terminally silylated PEGs with >95% silane incorporation. The resulting materials were applied to develop next-generation silicone-based adhesives with superior modulus and durability. This represents a significant advancement in elastic adhesive materials for demanding applications.