Original Article:
Recent Advances in the Synthesis of C2-Functionalized Pyridines and Quinolines Using N-Oxide Chemistry
Dong Wang, et al.
Advanced Synthesis & Catalysis, 2021, 363(1), 2-39.
10.1002/adsc.202000910
Nitrogen heterocyclic compounds are molecules that contain nitrogen atoms in their ring structure. Depending on the ring structure and the number of nitrogen atoms, common classes of nitrogen heterocycles include pyridine, pyrrole, pyrazine, pyrimidine, imidazole, and quinoline. Among them, pyridine and quinoline are the most common heterocyclic building blocks in medicinal chemistry and materials science, and many C2-functionalized pyridines and quinolines with biological activity have been identified.
In this work, the authors review available synthetic methods for introducing functional groups at the C2 position of pyridines and quinolines. It was noted that pyridine or quinoline nitroxides 3 can be readily prepared by oxidation of the corresponding nitrogen heterocycles with known reagents. Non-deoxygenative N-oxide functionalization requires the reduction of product 4. Various functional groups have been introduced at the C2 position of pyridines/quinolines in high efficiency under mild conditions., and the reaction types include:
1. Halogenation
2. Amination
3. Amidation
4. Hydroxylation
5. Alkoxylation and Aryloxylation
6. Sulfonylation
7. Alkylation
8. Alkenylation
9. Arylation
10. Trifluoromethylation
11. Miscellaneous
