Molecular roof for selective synthesis

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February 11, 2022

Meta-selective reactions enabled by remote steric control

RIKEN CSRS successfully developed a method for selective functionalization of arenes using an iridium (Ir) catalyst and a newly designed roof-like ligand.

Development of methods to functionalize organic molecules in one step has been intensely investigated in recent years, because these reactions can directly add valuable functionality to simple starting materials, and they can also enable the fast synthesis of complex medical and agricultural drugs and functional molecules. However, a serious problem remains largely unsolved: even simple organic molecules have many reaction sites, and selective reaction at the desired site is very difficult. In the case of arenes, a mixture of ortho, meta, and para products is often obtained, requiring tedious separation.

In this study, the research team designed a bioinspired catalytic system that creates a molecular pocket to fit the substrate only in a determined orientation, to achieve meta-selective functionalization of arenes. The catalytic system uses a roof-like ligand: a molecular “roof” was attached perpendicularly to 2,2’-bipyridine, a molecule well-known as a ligand for metal catalysts. They then found that the complex of Ir with this ligand enables meta-selective borylation of various arenes, because this roof-like ligand/Ir catalyst creates a molecular pocket that hinders the approach of the substrate in a para orientation. This reaction can be used to meta-selectively functionalize arenes including alkylbenzenes, anilines, and phenol derivatives, as well as complex drug molecules.

The findings of this study are expected to contribute to the development of selective and efficient techniques to synthesize medical and agricultural drugs and functional molecules.

Original article
Science doi:10.1126/science.abm7599
B. Ramadoss, Y. Jin, S. Asako, L. Ilies,
"Remote steric control for undirected meta-selective C-H activation of arenes".
Laurean Ilies; Team Leader
Sobi Asako; Senior Scientist
Advanced Organic Synthesis Research Team