After carbon and hydrogen; carbon, oxygen, nitrogen, and sulfur are the four of the most common elements found in pharmaceuticals and drug candidates. Lead identification and optimization is typically the longest part of the drug discovery process, taking about five out of the average fifteen years, to bring a drug to market. This is partially due to the requirement to synthesize and test of a large number of potential drug candidates through structure activity relationship (SAR) studies. As such, the development of new organic methodologies for the rapid synthesis of organic molecules is of utmost importance to synthetic chemists. The research described herein focuses on the development of novel approaches for the synthesis of C?N, C?S, C?O, and C?C bonds, in a selective and expedient manner. Moreover, it seeks to allow for divergent synthesis; where from a single common intermediate libraries of potential pharmaceuticals could be synthesized in a single synthetic transformation simply by varying the reagents. More specifically, the proposal focuses on the development of hydro- and oxidative functionalization of carbon-carbon double bonds using transition metal catalysts.
Regio-, chemo-, and stereoselective alkene functionalization reactions are developed for the synthesis of carbon?nitrogen, carbon?sulfur, carbon?oxygen, and carbon?carbon bonds. The use of transition metal catalysts enables these novel methodologies. Finally, mechanistic investigations into these powerful new methodologies are proposed.
| Kohler, Daniel G; Gockel, Samuel N; Kennemur, Jennifer L et al. (2018) Palladium-catalysed anti-Markovnikov selective oxidative amination. Nat Chem 10:333-340 |
| Gockel, Samuel N; Buchanan, Travis L; Hull, Kami L (2018) Cu-Catalyzed Three-Component Carboamination of Alkenes. J Am Chem Soc 140:58-61 |
