The control of site-selectivity is important to obtain the desired products efficiently in synthetic organic chemistry. Because there are many C-H bonds with similar reactivities in organic molecules, it was difficult to promote site-selective C-H transformations without using directing groups. In this award article, I describe new strategies to control site-selectivity in C-H transformations using noncovalent interactions, such as hydrogen bond, Lewis acid-base interaction and electrostatic interaction, between the catalyst and the substrate. As a result, highly site-selective C-H transformations have been achieved. By using Lewis acid-base interaction between the substrate and reagent, ortho-selective C(sp2)-H borylation and silylation were achieved. In addition, site-selective C(sp2)-H trifluoromethylation was developed by inclusion of the aromatic substrate into cyclodextrin by supramolecular interaction.
Dearomative functionalization is a powerful method to construct structurally complex alicyclic frameworks from simple and abundant aromatic molecules. Although a myriad of dearomative functionalizations have been reported so far, the reaction of electron-neutral arenes such as benzenes and naphthalenes are a still challenging issue due to their high aromatic stability, often requiring an excess amount of aromatic starting materials. Recently, we have developed catalytic dearomative functionalization of electron-neutral arenes by focusing on the unique reactivity of π-benzyl palladium catalysis. In this manuscript, we describe our endeavor to develop the dearomative C-C bond formations of benzyl alcohol derivatives, benzyl ammoniums, and bromoarenes. The dearomatized compound was transformed into various alicyclic skeletons by diverse derivatizations. Furthermore, we successfully achieved dearomative C-N bond formation with bromo(hetero)arenes, resulting in the synthesis of azaspirocycles. Utilizing the present methodology, the total synthesis of Cephalotaxus alkaloids with a unique complex polycyclic skeleton, has also been accomplished.
Picrotoxane-type sesquiterpenoids are a family of more than one hundred natural products, which bear a picrotoxane skeleton as the common structure. Among them, strong neurotoxic compounds, picrotoxinin, coriamyrtin, and tutin, have paid much attention from organic researchers as well as neuroscience researchers since the 1900’s. However, because almost all of the picrotoxane skeletons in the natural products are highly functionalized, the total synthesis of such natural products is challenging. This paper describes a method to stereoselectively synthesize the cis-fused 5,6-ring framework contained in the picrotoxane skeleton. A desymmetric strategy of the 2-methyl-1,3-cyclopentanedione moiety via the proline-mediated intramolecular aldol reaction provided the desired cis-fused skeleton. In addition, the total synthesis of coriamyrtin was achieved through the elaborate functionalization of the cyclopentane ring in the 5,6-ring framework obtained under our established intramolecular aldol reaction conditions.
Near-infrared (NIR) light (specifically 700-1000 nm) has garnered significant attention in recent years. Even though 52% of solar energy is infrared light, the utilization of energy in this region remains an area for improvement because most current natural and artificial materials do not interact with it. Organic synthesis provides a wide array of organic molecules. Therefore, developing novel dyes and pigments through synthetic organic chemistry is crucial to optimize the utilization of NIR light. Phthalocyanines and related macrocycles are well-known artificial dyes in modern materials chemistry. We are focusing on novel synthetic methods for phthalocyanines, creating novel phthalocyanine-based NIR chromophores, and developing novel NIR light-mediated molecular transformations using phthalocyanine catalysis. This article presents our recent findings on the chemoselective synthesis of photofunctional materials with intense NIR light interactions. The development of these materials requires precise control of the photoexcited state. Through fine-tuning NIR dyes, we have achieved highly robust photosensitizing agents, NIR light-mediated photodynamic therapy, and NIR light-driven organic reactions. Moreover, novel reaction environments with photofunctional materials can propose new applications for NIR light utilization. These achievements create further opportunities for the flexible application of NIR light.
Reduction and oxidation (redox) reactions are fundamental chemical processes and frequently involve single electron transfer (SET). Nicotinamide adenine dinucleotide is an eminent redox coenzyme, and the oxidized form (NAD+) is converted to the reduced form (NADH) for its use in biological redox processes. Benzimidazoline (BIH) and benzimidazolium (BI+) are recognized as artificial analogues of NADH and NAD+. Redox chemistry of BIH has started in the mid 80s in which 1,3-dimethyl-2-phenylbenzimidazoline (BIH-Ph) was used as a hydride donor. Subsequently, electron and hydrogen atom donating property of BIH-Ph was explored. Following thermodynamic as well as kinetic investigations of 2-substituted-1,3-dimethylbenzimidazolines (BIH-R) revealed that SET from BIH-R produces their radical cations (BIH-R•+) which release hydrogen atom to give the oxidized forms (BI+-R). Deprotonation of BIH-R•+ by appropriate bases produces radicals BI•-R which act as strong electron donors. We began to investigate photoinduced electron transfer (PET) reactions of BIH-R in the mid 90s. Breakthroughs of BIH-R redox chemistry were made in the areas of photocatalytic CO2 reduction as well as n-type doping to organic semiconductors around 15 years ago. Thus far, BIH-R have been utilized in various chemical processes and applications such as hydride reduction, photoredox catalysis, artificial photosynthesis, O2 reduction, and organic semiconductor devices. Redox chemistry of the oxidized form BI+-R which is much less explored than that of BIH-R has recently begun. In this review article, we described the brief history and the representative investigations of BIH-R. In addition, recent studies of BI+-R which are utilized as redox catalysts were presented.
In microdroplets sprayed from a nozzle with high-pressure nebulizing gas and high voltage, reactants are placed in a special reaction field where chemical reactions may occur in a different mode from those in bulk solvents. In this short review, recent examples of organic reactions in microdroplets are described.