Rhodium-catalyzed synthesis of unsymmetric di(heteroaryl) compounds via heteroaryl exchange reactions

Abstract

Unsymmetric di(heteroaryl) HetAr–X–HetAr′ compounds have flexible and rigid groups, and are expected to exhibit various biological activities by interacting with proteins and nucleic acids. Then, synthesis of such compounds is critical for the development of drugs. Unsymmetric HetAr-X-HetAr′ compounds were efficiently synthesized by rhodium-catalyzed heteroaryl exchange reactions, which involved equilibrium control by judicious design of organic heteroaryl reagents. This method allows synthesis of unsymmetric HetAr–O–HetAr′, HetAr–S–HetAr′, and HetAr–CH₂–HetAr′ compounds as well as HetAr–F compounds from heteroaryl aryl ethers and heteroaryl reagents. The rhodium-catalyzed heteroaryl exchange reaction was also applied to the synthesis of C–N-linked di(heteroaryl) compounds from N-benzoyl heteroarenes and heteroaryl aryl ethers. The synthesis has a broad applicability, which gives a diversity of novel unsymmetric HetAr–X–HetAr′ and C–N-linked di(heteroaryl)s compounds containing five- and six-membered heteroarenes.

GRAPHICAL ABSTRACT

Keywords:

• Heteroaryl exchange reaction
• rhodium-catalyzed reaction
• di(heteroaryl) sulfide
• di(heteroaryl) methane
• di(heteroaryl) ether
• C–N-linked bi(heteroaryl)s

Acknowledgments

Author is grateful thanks to Prof. Masahiko Yamaguchi for advice on experimental design, and thanks to Assistant Prof. Saori Tanii for her efforts in this study.

Additional information

Funding

This work was supported by the Platform Project for Supporting Drug Discovery and Life Science Research from AMED under Grant JP18am0101100, and JSPS KAKENHI Grant Nos. 17K19112 and 15H00911.