Synthetic organic chemistry pursues the methodology for making molecules in a highly precise manner. It has been long studied and some chemists even think that we can synthesize any compounds if enough time and resources are given. However, the resource in our world is not inexhaustible, of course. We need to synthesize valuable organic molecules such as polymers, OLED, and pharmaceuticals, with minimizing waste and consumption of precious resources. Furthermore, for the discovery of new materials and drugs, organic compounds that can be easily synthesized are mainly investigated, leaving a large part of chemical spaces unexplored. Our research group is struggling to address these problems through the discovery of new organic reactions. We are especially focused on the development of original catalysts and reagents.

  1. Transition metal-catalyzed C–H activation
  2. 光触媒（Photoredox Catalyst）と遷移金属触媒を組み合わせた新規触媒系の研究
  3. Organic reactions using highly reactive hypervalent iodine reagents
  4. Chiral paddle-wheel diruthenium catalysis

1. Transition metal-catalyzed C–H activation

In a fundamental organic chemistry class, we learn that many organic reactions occur around functional groups, such as alkene, alkyne, halogen, carbonyl, hydroxy, amine, and etc. Thus, when we plan a synthetic route of desired molecules via retro-synthesis, appropriate functional groups must be pre-installed where we want to make a new bond.  If we could selectively transform a desired carbon–hydrogen bond in organic compounds into any functional group as we want, we would be able to construct a complex molecule from inexpensive hydrocarbon-based feedstocks. Such a methodology is called Catalytic C–H activation or C–H functionalization and has been extensively studied all over the world.

We have been studied transition metal catalysts involving trivalent group 9 metals, namely cobalt(III), rhodium(III), and iridium(III) bearing a cyclopentadienyl type ligand (Cp ligand). In 2013, we first reported the use of Cp*CoIII catalyzed C–H activation [ACIE. 2013]. After our seminal report, many other research groups in the world have used this cobalt catalyst for the development of new reactions. Our group has developed a variety of synthetic organic reactions based on the unique reactivity of the cobalt catalyst compared to rhodium and iridium catalysts.

We have been working on the development of enantioselective (asymmetric) C–H activation and functionalization reactions with the combination of rhodium or cobalt catalysts and external chiral sources. Asymmetric catalysis is an important methodology for the synthesis chiral building blocks for drug and other complex molecules using a small amount of a chiral source. We realized various asymmetric C–H functionalization reactions using chiral sulfonates, carboxylic acids, and a Lewis base catalyst, which cooperatively work with easily available achiral simple metal catalyst.

Representative publication
Cobalt-catalyzed C–H activation
Asymmetric C–H activation/functionalization
C–H activation using electron-deficient Cp-metal catalysts

2. 光触媒（Photoredox Catalyst）と遷移金属触媒を組み合わせた新規触媒系の研究

　現代社会を支える化学製品や医薬品などの高付加価値物質のほとんどは、熱エネルギーを駆動力とする「熱反応」により生産されています。しかし近年、太陽光に由来するクリーンかつ無尽蔵なエネルギー源である可視光を活用し、特異な化学反応を実現する「光触媒反応」が多く報告され、モノづくりにおける画期的な方法論として熱い注目を集めています。

　私たちは光触媒反応を武器に、「ありふれた元素の隠された可能性を引き出す」ことに注力しています。例えばコバルトは安価で多量に入手できますが、熱反応の触媒として活躍する例はいまだ限られています。驚くべきことに、コバルトは光により活性化すると、触媒としてより一般的に用いられる希少金属（ロジウム、イリジウム）を凌駕する優れた性能を発揮することを、我々は世界に先駆けて発見しました[ACIE. 2019]。

　熱反応を主軸とする化学では見過ごされてきた分子も、光の下では全く新しい表情を見せはじめます。持続可能性に優れた方法論として、また熱反応とは一線を画す新たな化学反応の発見を目指して、光反応の可能性を追求したいと考えています。

Representative publication

3. Organic reactions using highly reactive hypervalent iodine reagents

Main group elements generally form covalent bonds to fulfill so-called octet rule, but heavy elements often form more covalent bonds, which we refer to as hypervalency or hypervalent compounds. Hypervalent iodines have three or more covalent bonds around the iodine center. Several hypervalent iodine reagents are commercially available and frequently used as non-metal reagents for organic synthesis. While those reagents have at least one aromatic substituent and are enough stable and easily-handled, their reactivity is somewhat attenuated due to the stabilization.

We have been focused on the high reactivity of hypervalent iodine reagents with only oxygen substituents on the iodine center; ITT (iodine tris(trifluoroacetate)) and iodine triacetate. We found that these reagents react with aryl Si/Ge/Sn/B nucleophiles to directly afford aryl iodanes under very mild reaction conditions. As further application, we developed astatination using spirocyclic iodonium ylides [OBC.2021]. Astatine is a halogen atom next to iodine and has no stable isotopes. At-211 is an α-emitting nuclide produced by a cyclotron and its application to targeted α-therapy for cancer is under investigation. We are also working the development of At-211 labelling system collaborated with other research teams.

　　In 2021, we revealed that ITT oxidizes simple tetraalkylsilanes at low temperatures [JACS. 2021]. Although the oxidation of silanes into alcohols is well-known as Tamao-Fleming oxidation, direct oxidation of simple tetraalkyl silanes are very difficult under standard reaction conditions. This reaction highlights the notable reactivity of ITT and we are now working on finding new synthetic reactions using ITT.

Representative publication

4. Chiral paddle-wheel diruthenium catalysis

　Chiral paddle-wheel dimetal complexes have two adjacent metal atoms surrounded by four chiral bridging ligands. Chiral dirhodium (Rh-Rh) complexes have been well studied for catalytic asymmetric synthesis and a huge number of applications have been reported to date. In 2020, we found that chiral paddle-wheel diruthenium (Ru-Ru) complexes also work as efficient catalysts for asymmetric reactions [Nat. Catal. 2020]. These diruthenium complexes have higher oxidation state (RuII-RuIII), Lewis acidity, and stability towards oxidation than dirhodium complexes. We have been developed new reactions the unique features of the diruthenium complexes.

Representative publication