Nucleophilic C4-selective (hetero) arylation of pyridines for facile synthesis of heterobiaryls

Abstract

The synthesis of heterobiaryl compounds holds significant value in organic chemistry due to their extensive range of applications. Herein, we report a highly efficient strategy for conducting C4-selective (hetero) arylation of pyridines using N-aminopyridinium salts. The reaction proceeds readily at room temperature in the presence of a base, thus eliminating the requirement for catalysts or oxidants. This method allows for the installation of various electron-rich (hetero) aryl groups on pyridines, resulting in the streamlined synthesis of highly valuable C4-(hetero) aryl pyridine derivatives, which are otherwise challenging to acquire via conventional methods. This simple and straightforward method will facilitate access to a range of heterobiaryl compounds thereby promoting their application in various scientific disciplines.

Keywords: C-H (hetero) arylation; C4-selectivity; heterobiaryl; metal-free; pyridinium salt.