Date & Time: Apr 10 2025 | 11:10am - 12:10pm Location: iSTEM Building 2, Room 1218 Late-stage functionalization, a transformative strategy in medicinal chemistry, enables precise modification of molecular frameworks through atom insertion, deletion, or exchange, offering rapid access to novel pharmacophores and enhancing drug discovery efforts. Nitrogen-containing heterocycles, such as indoles, pyrroles, and pyridines, are pivotal in pharmaceuticals.[1] Yet, existing methods for their diversification by nitrogen insertion often rely on harsh reaction conditions [6], protective-group strategies [7], or limited substrate scope. Recent works have addressed these challenges by presenting innovative approaches to skeletal editing that expand synthetic accessibility and efficiency. First, Morandi's group leveraging the dual role of lithium bis(trimethylsilyl)amide (LiHMDS) as both a base and nitrogen source, the authors demonstrate direct N-atom insertion into unprotected 1H-indoles and 1H-pyrroles, bypassing prefunctionalization steps and enabling late-stage modification of bioactive molecules. In 2025, the Sharma group addressed the limitation of the use of heavy metal oxidative by introducing sulfenylnitrenes—underutilized intermediates bearing a thio-functional leaving group—as a versatile platform for single nitrogen-atom incorporation. Lastly, Zheng and Houk's group reported advances in pyridine skeletal editing through ring expansion and rearrangement strategies, utilizing pyridinium salt intermediates and energy-ring expansion to access structurally diverse heterocycles. Reference: Njardarson T., J. Med. Chem. 2024, 67, 11622−11655 Morandi et al., Org. Lett. 2023, 25, 8419−8423 Sharma et al., Science, 2025, 387, 102–107 Zheng & Houk et al., J. Am. Chem. Soc. 2024, 146, 21389−21400 E. Beckmann, Ber. Dtsch. Chem. Ges. 1886, 19, 988-993. K. Maeda, T. Mishima, T. Hayashi, Bull. Chem. Soc. Jpn. 1974, 47, 334–338 P. R. Kumar, Heterocycles 1987, 26, 1257–1262. D. H. Barton, I. A. Blair, P. D. Magnus, R. K. Norris, J. Chem. Soc., Perkin Trans. 1973, 11037–1040 R. S. Atkin son, B. D. Judkins, D. R. Russell, L. J. Sherry, J. Chem. Soc., Perkin Trans. 1985, 11967–1969. Type of Event: Organic Seminar Research Areas: Organic Chemistry Shivani Nagode Department: Graduate Student, Department of Chemistry University of Georgia Learn more about the speaker https://chem.uga.edu/directory/people/shivani-nagode
