Most medicines and functional materials are synthesized by introducing functional groups into an aromatic ring of substrates. Many kinds of reactions and catalysts have been developed, but it is still not easy to selectively introduce a functional group into the specific position of aromatic rings. Especially, more efficient and selective reactions to functionalize a meta-position, which is the most difficult one for substitution, should be developed to overcome the following problems: (1) limitation of substrates; and (2) contamination of byproducts, in which the desired reaction occurs at ortho- and/or para-positions.
A research group at The University of Tokyo designed and synthesized a new catalyst that can selectively introduce a functional group into a meta-position of aromatic compounds. The catalyst is constructed from “Reaction part”, which promotes a substitution reaction, “Recognition part”, which recognizes a functional group of aromatic substrates by hydrogen bonding, and “Crosslinking part”, which crosslinks between these two parts (Figure 1). By using this catalyst, the research group has succeeded in meta-position-selective substitution reaction under mild conditions even in a gram-scale. The catalytic system will contribute to the development of more efficient synthetic methods for the synthesis of new medicines and functional materials.
The catalyst is constructed by “Reaction part” (orange), “Recognition part” (green), and “Crosslinking part” (blue) (Figure 1). Two hydrogen atoms (white sphere) at “Recognition part” make hydrogen bonding with an oxygen atom (red sphere) of a functional group of an aromatic ring (gray) of a substrate. Hydrogen-bonding is shown by a red dotted line.
First, hydrogen-bonding (red dotted line) is formed (Figure 2). Second, “Crosslinking part” brings “Reaction part (with Iridium metal)” close to a meta-position of an aromatic ring. Finally, a hydrogen atom at the meta-position is replaced with the desired functional group (brown box).
Figure 1: Design of the group’s catalyst that can selectively introduce a functional group
into meta-position on an aromatic ring
Figure 2: Reaction mechanism of the research group’s catalyst
Kanai Life Science Catalysis Project
Yoichiro Kuninobu, Haruka Ida, Mitsumi Nishi, and Motomu Kanai, “A meta-selective C–H borylation directed by a secondary interaction between ligand and substrate”. Nature Chemistry, 2015; 7, 712–717, doi: 10.1038/nchem.2322.
Motomu Kanai, Ph.D.
Principal Investigator of ERATO “Kanai Life Science Catalysis Project” / Professor, Graduate School of Pharmaceutical Sciences, The University of Tokyo
Yoichiro Kuninobu, Ph.D.
Group Leader of ERATO “Kanai Life Science Catalysis Project” / Associate Professor, Graduate School of Pharmaceutical Sciences, The University of Tokyo
Department of Research Project, JST
K’s Goban-cho 7, Goban-cho, Chiyoda-ku, Tokyo102-0076 Japan