Armido Studera; University of Münster, Germany
"Regioselective Pyridine C-H-Functionalization and Skeletal Editing"
Pyridines belong to the most abundant heteroarenes in medicinal chemistry and in agrochemical industry. In the lecture, highly regioselective pyridine C-H functionalization through a dearomatization/rearomatization sequence will be discussed. The dearomatized oxazino pyridines can be easily prepared on a large scale, and meta-functionalization becomes achievable through light-initiated radical alkylation and ionic transformations.1 As example, using such an approach meta-fluorinated pyridines are readily accessible.2 The same intermediates upon protonation to give the corresponding pyridinium salts also allow the highly regioselective radical Minisci para-alkylation.3,4 In addition, Cu-catalyzed meta-arylation5 and switchable radical para/meta-difluoromethylation6 through such intermediates will be presented. Radical meta-nitration7 and ionic meta-hydroxylation8 work equally well through such intermediates. Finally, it will be shown that this dearomatization concept is also applicable to pyridine skeletal editing.9 Further, it will be discussed that an alternative radical dearomatization process can be used for C to N mutation in indoles and benzofurans.10
References
1. Cao, H.; Cheng, Q.; Studer, A. Science 2022, 378, 779. For a review, see: Bhattacharya, D.; Haring, M.; Studer, A. Chimia 2025, 79, 476.
2. Haring, M.; Balanna, K.; Cheng, Q.; Lammert, J.; Studer, A. J. Am. Chem. Soc. 2024, 146, 30758
3. Cao, H.; Bhattacharya, D.; Cheng, Q., Studer, A. J. Am. Chem. Soc. 2023, 145, 15581.
4. Wang, Z.; Xu, P.; Studer, A. Org. Chem. Front. 2024, 11, 3849.
5. Guo, S.-M.; Xu, P.; Studer, A. Angew. Chem. Int. Ed. 2024, 63, e202405385.
6. Xu, P.; Wang, Z.; Guo, S.-M.; Studer, A. Nat. Commun. 2024, 15, 4121.
7. Balanna, K.; Studer, A. J. Am. Chem. Soc. 2025, 147, 7485.
8. Bhattacharya, D.; Studer, A. Angew. Chem. Int. Ed. 2025, 64, e202423512.
9. Cheng, Q.; Bhattacharya, D.; Haring, M.; Cao, H.; Mück-Lichtenfeld, C.; Studer, A. Nat. Chem. 2024, 16, 741.
10. Wang, Z.; Xu, P.; Guo, S.-M.; Daniliuc, C. G.; Studer, A. Nature 2025, 642, 92.