RIKEN develops solid catalyst for efficient C-H boronylation

A research group including Team Director Yoichi Yamada and Research Scientist Zhenzhong Zhang of the Green Nanocatalysis Research Team at the RIKEN Center for Sustainable Resource Science prepared a recoverable and reusable polymer-supported iridium (Ir) catalyst. The group developed a C-H boronylation reaction of aromatic compounds under both batch and continuous flow reaction conditions. This presents a new preparation method for immobilized transition metal catalysts, and application is expected toward continuous flow organic synthesis processes for the synthesis of functional molecules and their intermediates. The findings were published in the online edition of Communications Chemistry.

Organoboron compounds are widely used in the development of pharmaceuticals, agrochemicals, and functional molecules. Among the synthesis methods for these compounds, activating carbon-hydrogen bonds to directly introduce a boronic ester structure into aromatic compounds has attracted attention in recent years as a method with extremely low waste and high atom efficiency (the conversion efficiency of atoms in a chemical reaction). However, the monovalent Ir complex widely used as a transition metal catalyst in this reaction is expensive, and it is difficult to recover and reuse after the reaction.

On the other hand, in recent years, switching from batch reactors such as flasks and reaction vessels to flow reaction systems, especially continuous flow reaction systems packed with heterogeneous catalysts (solid catalysts), is considered effective. This switch increases reaction efficiency by achieving rapid mixing and a larger specific surface area (the value obtained by dividing the surface area of a substance by its mass or volume). Also, it improves safety and environmental compatibility through easy temperature management and residence time control.

However, among the immobilized Ir catalysts developed so far, no example of application to a continuous flow C-H boronylation reaction that can be conducted in air has been reported.

The research group previously developed a functional copolymer containing a pyridine (C₅H₅N) structure. By utilizing a bulky tert-butyl group, they dispersed the palladium species introduced into the molecule and prepared a heterogeneous catalyst with excellent stability. By using this catalyst, a continuous flow Suzuki-Miyaura cross-coupling reaction can be promoted over a long period of time. Therefore, in these developments, they investigated applying this method to immobilize Ir species and prepare a stable catalyst.

First, using pyridine as a coordination site, a derivative of styrene (which is an aromatic hydrocarbon) was introduced into a polymer structure to prepare various functional copolymers. As for the catalyst preparation method, they developed a method to immobilize a monovalent Ir species generated by reduction from a trivalent Ir precursor in a mixed solvent of ethanol and water, using the copolymer containing the pyridine structure.

Using the prepared catalyst, they investigated the C-H boronylation of anisole (an aromatic ether) using a batch system. As a result of examining polymer-supported Ir catalysts of various structures, it was found that a ternary copolymer synthesized from 4-vinylpyridine, 4-tert-butylstyrene, and N-isopropylacrylamide was effective for the immobilization and stabilization of Ir species.

When reaction conditions were optimized using the polymer-supported Ir catalyst obtained through this, the C-H boronylation of anisole was achieved with a GC (gas chromatography) yield of 74%. Under the optimized reaction conditions, 1.2 mol% of the Ir catalyst was used, and the reaction was performed at 125℃ for 24 hours using decane as a solvent. The Ir residue detected in the product was 0.5 ppm or less, clarifying that the metal residue was low. Furthermore, it was confirmed that the catalyst after the reaction could be recovered by centrifugation and reused after washing (yield of 65% upon reuse).

When the scope of substrates was investigated using the optimized reaction conditions, benzene rings substituted with electron-donating groups and electron-withdrawing groups could be applied under these reaction conditions. The C-H boronylation reaction also proceeded smoothly for heterocyclic compounds often contained in functional organic materials, such as pyridine, indole, benzofuran, and benzothiophene. In particular, a derivative of thiophene, which is a sulfur-containing heterocyclic compound, showed high reactivity, and the boronylated product was obtained with a maximum yield of 87%.

Next, the optimized polymer-supported Ir catalyst was mixed with sea sand and packed into a cartridge-type column to investigate the continuous flow C-H boronylation reaction. In the experiment, the B₂pin₂ reagent was dissolved in 1,2-dichlorobenzene, and the resulting clear solution was fed into the column using a syringe pump. The reaction was conducted in air at 140℃. It was performed for 6 hours a day for 4 days, totaling 24 hours.

After the completion of the reaction each day, the polymer-supported Ir catalyst was kept inside the flow apparatus, and there was no need to use an inert gas. Because the product yield is calculated based on B₂pin₂, the theoretical maximum value is 200%. As for the experimental results, an induction period (the time until sufficient active species are generated) was observed in the first day's reaction. After that, the product yield improved to 180% or more. From the second day onward, the reaction proceeded stably, no decrease in yield was seen during the 4-day operation, and the total yield reached 181%.

Journal Information
Publication: Communications Chemistry
Title: Polymeric iridium catalysts for C-H borylation of arenes under batch and continuous flow conditions
DOI: 10.1038/s42004-026-02044-0