Acyl ammonium cations can be readily prepared from inexpensive and commercially available nucleophilic tertiary amines and acid chlorides or chloroformates. The significantly electrophilic nature of these cations allows rapid acylations to occur. However, it also causes undesired reactions. The emergence of micro-flow technologies has enabled precise control of reaction time (< 1 s) and temperature that cannot be achieved by conventional batch technologies. In this account, we describe high-yielding, rapid, less wasteful, and low-cost syntheses of peptides and amino acid derivatives via highly electrophilic acyl ammonium cations in which undesired reactions were suppressed by micro-flow technologies. These technologies not only enabled the development of highly efficient synthetic processes, but also provided us deeper insights into the highly active acyl ammonium cation species involved. This is leading to novel discoveries regarding their value in synthesis.

The selective and predictable C-H functionalization of arenes is a valuable method for the synthesis and modification of organic molecules in which regioisomer formation is often controlled by electronic factors or the presence of coordinating groups. On the other hand, the iridium-catalyzed C-H borylation of arenes can achieve unique steric-controlled regioselectivity. In this account, we describe our recent studies on the iridium-catalyzed C-H borylation of arenes: the development of novel catalytic systems that exhibit steric-controlled para-selectivity for mono- and unsymmetrically 1,2-disubstituted benzenes; and their application to the functionalization of large polycyclic aromatic hydrocarbons (molecular nanocarbons).

In recent years, carbon-fluorine (C-F) bond transformation for organic synthesis has been remarkably developed. Herein, we describe four types of C-F bond transformation mediated by Lewis acids: (1) C(sp²)-F bond transformation of gem-difluoroalkenes through oxyindation/β-fluorine elimination to afford fluorinated isocoumarins; (2) B(C₆F₅)₃-catalyzed substitution of fluorine in 1-fluorostyrenes with silyl ketene acetals via abstraction of F⁻ by in situ generated silylium ions; (3) BF₃-catalyzed formal insertion of diazoesters into the C-F bonds of benzylic fluorides; and, (4) photoredox catalyst/Lewis acidic Sn species-mediated C(sp³)-F bond allylation of perfluoroalkylarenes. Density functional theory (DFT) study of the reaction mechanisms suggests the importance of choosing the appropriate Lewis acid to achieve an appropriate activation method for the C-F bonds in each reaction.

Trivalent iodine compounds have found widespread applications as oxidants and electrophilic group-transfer agents for organic synthesis. Over the last several years, our group has developed new reactions and synthetic methods of a class of stable trivalent iodine compounds known as benziodoxol(on)es. This article summarizes our studies on (1) new palladium-catalyzed transformations of ethynylbenziodoxol(on)es beyond alkynyl group transfer and (2) the use of benziodoxole triflate as a cationic iodine(III) electrophile for the functionalization of alkynes and arenes, illustrating how the unique reaction chemistry of trivalent iodine can be utilized to achieve synthetically attractive transformations and open up access to previously inaccessible molecular building blocks.

Helicenes have excellent chiroptical properties derived from their helical chirality and so attract the attention of scientists for their potential application to chiral organic functional materials. Thus, developing an enantioselective synthetic method for helicenes is an important goal in organic synthesis. Here we describe the enantioselective synthesis of helicene and helicene-like molecules by cationic rhodium(I)/bisphosphine complex-catalyzed [2+2+2] cycloaddition reactions. The enantioselective intramolecular [2+2+2] cycloaddition reactions of 2-naphthol-linked triynes afford [7]helicene-like molecules in good yields and ee. [9]Helicene-like molecules and fully aromatic carbo[7]helicenes can also be synthesized enantioselectively by intramolecular [2+2+2] cycloaddition reactions. The enantioselective sequential intramolecular [2+2+2] cycloaddition reactions of variously linked hexaynes afford either a [11]helicene-like molecule or an S-shaped double helicene-like molecule, both in high ee. Cationic rhodium(I)/biaryl bisphosphine complexes can catalyze not only intramolecular reactions, but also intermolecular ones between tetraynes and 1,4-diynes to afford [7]-[9]helicene and helicene-like molecules. We also describe some representative examples of the enantioselective synthesis of helicene and helicene-like molecules by [2+2+2] cycloaddition reactions using transition metal catalysts other than rhodium (iridium, nickel, and palladium).

Fluorine-containing organic molecules are expected to be used in various applications, and radical reactions are considered useful synthetic methods. Visible-light-induced organic reactions using photoredox catalysts continue to be investigated and their application to the synthesis of fluorinated compounds has been reported. We have developed organocatalytic perfluoroalkylation through environmentally friendly visible-light-driven reactions. In this account, we introduce our recently developed visible-light-driven perfluoroalkylation of electron-rich olefins catalyzed by eosin Y and enamines.

Stimuli-responsive materials attract considerable attention as sources of future innovation but many difficulties remain in establishing their precise control. Consequently, examples that display crystallinity both before and after a response to a stimulus are useful in determining structure-property relationships. In this account, I describe various crystalline materials composed of three kinds of structural motif (triangular, bowl-shaped, and cross-shaped), all of which, on stimulation, show changes in their structures and properties while retaining a high degree of crystallinity.

The development of biomarkers is key to the discovery of novel drugs. Positron emission tomography (PET) tracers are powerful noninvasive neuroimaging biomarkers which enable to monitor the target engagement of the central nervous system (CNS) drugs. This report describes the design, synthesis, and identification of specific PET tracers for CNS drug targets, namely, monoacylglycerol lipase ([¹⁸F]T-401), diacylglycerol kinase gamma ([¹¹C]T-278), lysine-specific demethylase 1 ([¹⁸F]T-914) and cholesterol 24-hydroxylase ([¹⁸F]T-008), based on screening flow customized for PET tracer discovery. Analyzing PET images of rodents and non-human primates confirmed that these tracers could serve as biomarkers to support the development of novel drugs.

Artificial photosynthesis mimics natural photosynthesis and involves oxidation and reduction half-reactions, both of which are small-molecule transformations. Given that the realization of artificial photosynthesis may alleviate the energy and environmental problems faced by humankind, the development of catalysts for such transformations is a task of great practical significance. Our analysis of the natural photosynthetic system suggests that efficient small-molecule conversion requires the related catalysts to have (1) an active center with good reactivity, (2) charge-transporting sites close to the active center, and (3) substrate-transporting channels. Herein, we describe our recent progress in the development of small-molecule conversion catalysts based on this consideration and our original concept of function integration.

As the next generation optoelectronic devices, i.e., post- organic light emitting diodes (OLEDs), organic semiconductor laser diodes (OSLDs) are supposed to be fascinating devices due to their unique properties such as a wide range of emission wavelength tunability, low-temperature fabrication allowing flexible devices, and the compatibility with present OLED technologies. In this report, by focusing on the most promising laser material of 4,4’-bis[(N-carbazole)styryl]biphenyl (BSBCz), the materials design of organic lasing molecules with their photophysical and current injection device properties are summarized.