To achieve sustainable development of synthetic chemistry, the author has developed “flash organic synthetic chemistry” enabled by the originally developed flow microreactor system. Acceleration of whole factors concerning the organic chemistry processes—reactions, synthesis, manufacturing, and research & development—is indispensable for achieving the environmentally benign processes that can reduce the energy consumption, harmful wastes, and even the manual processes by human beings. This article describes the author’s developments with a focus on the insights that enable to synthesize what we need, to avoid cryogenic manipulations, to skip protective groups, to speed-up research, and to achieve mass production.

Hydration of unsaturated organic compounds is extensively utilized in organic synthesis. Classical methods using strong acids or bases often lead to the undesired decomposition of other functional groups, necessitating the pursuit of chemoselective and catalytic approaches. Although various catalysts have been developed to facilitate the hydration of unsaturated organic compounds, achieving chemoselective hydration of functionalized substrates remains a challenge. This review presents our recent works in the development of catalytic systems that hydrate specific functional groups through precise control of the catalyst structure and the reaction environment. In particular, our research on alkyne hydration and (transfer) nitrile hydration is featured.

Diradicals have been actively studied because of their unique electronic structures and properties not observed in closed-shell molecules. Quinodimethane is one of the basic motifs of diradicals. p-quinodimethane (p-QDM) and o-quinodimethane (o-QDM) are singlet Kekulé hydrocarbons, while m-quinodimethane (m-QDM) is a triplet non-Kekulé hydrocarbon. Most of the hydrocarbon diradicals studied to date have been limited to non-fused-ring and fused-ring open-shell singlet diradicals based on p-QDM and o-QDM and non-fused-ring triplet diradicals based on m-QDM.

In this study, various fused-ring diradicals based on m-QDM, that is, quinoidal and zwitterionic open-shell singlet diradicals and non-Kekulé and Kekulé triplet diradicals, have been designed, synthesized, and isolated as crystals. Their electronic structures and properties have been elucidated by optical, electrochemical, and magnetic measurements and DFT calculations. The keys to the success include original molecular designs to control the interaction of unpaired electrons and developments of methods for introducing substituent groups at appropriate positions and purifying reactive diradicals.

During the last 30 years, the field of “fluorous chemistry” has witnessed intriguing advancements in organic synthesis. Fluorous molecules possess an alluring characteristic of displaying remarkably high affinity towards similar molecules, despite not mixing well with organic solvents or water. This phenomenon is commonly referred to as the “fluorophilic effect.” As we stand on the brink of the 30th anniversary of the inception of fluorous chemistry, this paper introduces our recent research accomplishments concerning the utilization of intermolecular or intramolecular fluorophilic effects in synthetic reactions.

Covalent drugs render potent and durable activity by chemical modification of the endogenous target protein under live cell conditions. To maximize the pharmacological efficay while alleviating the risk of toxicity arising from non-specific off-target reactions, current covalent drug discovery focuses on the development of targeted covalent inhibitors (TCIs). In the design of TCIs, an electrophilic reactive group (warhead) is strategically incorporated onto a reversible ligand of the target protein to facillitate specific covalent engagement. Various aspects of warheads, such as intrinsic reactivity, chemoselectivity, reaction mechanism, and reversibility of the covalent engagement, would affect the target selectivity of TCIs. While covalent targeting of cysteines by acrylamide-type Michael acceptors have been the most successful strategy in covalent drug discovery, a wide array of novel warheads have been devised and tested for designing TCIs in recent years. This review provides an overview of chemistry for selective covalent targeting of endogenous proteins under live cell conditions and its applications in TCI designs.

Highly strained cyclic compounds such as arynes and cyclic alkynes are important building blocks in organic synthesis. However, cyclic allenes have received far less attention. Herein, recent progress in the cycloaddition reaction using highly strained 6-membered allenes will be discussed.