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.

There is a famous sentence in Tao Te Ching: “The Tao produced one. One produced two. Two produced three. Three produced all things.” In this front cover picture, Tai Chi stands for Tao, and “N” and “O” in the two circles represent N‐oxides of this paper. Thunder and lightning stimulate Tai Chi to produce everything, which is represented by the five elements of metal, wood, water, fire, and earth. Therefore, this picture indicates that pyridine N‐oxides can produce numerous nitrogen‐containing heterocyclic compounds under the action of activating reagent. Details can be found in the Review by Dong Wang and co‐workers (D. Wang, L. Désaubry, G. Li, M. Huang, S. Zheng, Adv. Synth. Catal. 2021, 363, 2–39; DOI: 10.1002/adsc.202000910).

This study reports the invention of di‐ or trifunctionalization of readily available pyridines (including all the pyridine substrates utilized in this paper, such as 3‐cyanopyridine and 3‐chloropyridine) through dearomative functionalization‐oxidative rearomatization under transition‐metal‐ and reductant‐free conditions. Although a two‐step operation is required, the crude product of the first step could be used in the next step directly. Typically, 3‐π‐EWG pyridines undergo difunctionalization, whereas 3‐σ‐EWG pyridines participate in trifunctionalization, affording multisubstituted piperidines. Computational studies provide detailed insights for their distinct reactivity in the title reaction.

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A rapid, practical and scalable method for the reductant and tansition-metal-free synthesis of a variety of novel 2,4-disubstituted tetrahydropyridines and tetrahydroquinolines is disclosed. The method is based upon dearoma-tive functionalization of pyridines or quinolines to generate amino nitrile intermediates as masked iminium ions, which then react rapidly with various Grignard reagents in complete stereocontrol.[a] S. Zheng (郑世鑫), M. Huang (黄民栋), Prof. P. Yu (郁彭)