Heterocycles are among the most significant structural components of pharmaceuticals. Among the unique small-molecule drugs in U.S. FDA database, nearly 60% contains at least one N-heterocycle. N-Heterocycles possess essential properties including hydrogen bonding interactions and favorable physicochemical properties. Given the composition, frequency, and structural diversity in drug molecules, development of efficient synthetic methods for N-heterocycles is highly important. In this talk, several approaches for the synthesis of heterocycles will be discussed. Reactive intermediates including carbenes and radicals serve as powerful tools for bond formation. To access these reactive species, we have explored the reactivity of transition metal catalysts, photocatalysts, and electrolysis, which led to the discovery of unique annulation reactions that allowed the synthesis of various heterocycles. Considerable efforts have been made to establish the mechanistic understanding in depth. Moreover, we were able to extend the synthetic methodology toward the modification of biomolecules, and the details on the development of site-selective post-synthetic labeling of oligonucleotides will be discussed. References Choi, S.; Park, J.; Yu, E.; Sim, J.; Park, C.-M. Electrosynthesis of Dihydropyrano[4,3-b]indoles Based on a Double Oxidative [3+3] Cycloaddition. Angew. Chem. Int. Ed. 2020, 59, 11886. Ha, S.; Lee, Y.; Kwak, Y.; Mishra, A.; Yu, E.; Ryou, B.; Park, C.-M. Alkyne–Alkene [2 + 2] cycloaddition based on visible light photocatalysis. Nature Commun. 2020, 11, 2509. Lee, Y.; Yu, E.; Park, C.-M. Programmable Site-selective Labeling of Oligonucleotides Based on Carbene Catalysis. Nature Commun. 2021, in press.