Recent Advances in the Synthesis of C2-Functionalized Pyridines and Quinolines Using N-Oxide Chemistry

While remarkable progress has recently been made for the direct C-H-functionalization of azines, its application is still limited by a lack of accessible functional groups (primarily carbon-based) and poor regioselectivity. In contrast, C2-functionalized pyridines and quinolines can be easily synthesized by treating readily available N-oxides with various reagents under appropriate activation conditions. This review seeks to comprehensively document the available synthetic methods for introducing functional groups at the C2 position of pyridines and quinolines. In this work, we highlight recent developments in the C2-functionalization of pyridine and quinoline N-oxides and address both the mechanisms and regioselectivity of the reactions. We also describe the pathways and reactive species involved in these processes and highlight a number of medically relevant nitrogen heteroaromatics.

Automated summary

Recent progress has been made in the direct C-H functionalization of azines, but limitations still exist. In contrast, C2-functionalized pyridines and quinolines can be easily synthesized under appropriate activation conditions.