Site-selective functionalization of arenes using a catalyst control strategy

2019 Fiscal Year Annual Research Report

• Project/Area Number: 18F18777
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: イリエシュ ラウレアン 国立研究開発法人理化学研究所, 環境資源科学研究センター, チームリーダー (40569951)
• Co-Investigator(Kenkyū-buntansha): KULESHOVA OLENA 国立研究開発法人理化学研究所, .環境資源科学研究センター, 外国人特別研究員
• Project Period (FY): 2018-11-09 – 2021-03-31
• Keywords: organic synthesis / catalysis

Outline of Annual Research Achievements

The proposed research aims at the development of regioselective functionalization of simple arenes, through the design of bifunctional ligands capable of recognizing the substrate intermolecularly through non-covalent interactions.
During FY2020, we discovered that a terpyridine ligand ortho-substituted with an aryl group enables unprecedented iridium-catalyzed ortho-borylation of fluoroarenes, and cobalt-catalyzed meta-borylation of fluoroarenes. While we were studying the origin of difference in selectivity for the two metal catalysts, DFT calculation, followed by mechanistic experiments suggested that the iridium species first activates the C-H bond of the ligand to create a cyclometalated iridium catalyst, and polarity matching of this iridium catalyst with the fluorobenzene substrate makes the activation of the ortho C-H bond favorable by about 3 kcal/mol. We further investigated the mechanism through NMR studies, to reveal that the iridium catalyst first activates a C-H bond of the ligand, and the resulting cyclometalated iridium complex is the active species that reacts with fluorobenzene. A preliminary investigation of the reaction scope revealed that a variety of fluorobenzenes react with high ortho selectivity.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Catalyst/substrate polarity matching is an unprecedented way of controlling reaction selectivity, and it has the potential to become a general guiding principle for achieving selectivity in the reaction of simple polar substrates.

Strategy for Future Research Activity

During FY2020 we plan to further study the concept of catalyst/substrate polarity matching, especially from a mechanistic point of view, for example NMR experiments to identify key intermediates, kinetic studies, and more detailed DFT studies. Based on the mechanistic understanding, we will then refine the ligand design
in order to maximize dipole interaction, and achieve high regioselectivity. With the optimal ligand in hand, we will then investigate the substrate scope for the iridium-calayzed borylation of fluoroarenes. Finally, we will explore the generality of this concept, to achieve regioselective metal-catalyzed C-H activation of polar substrates.