Our group is interested in the development of selective C-C bond forming methods and the use of these methods in the synthesis of bioactive compounds. We are also interested in the application of our methods in domino sequences.
Presently, we are investigating:
- Efficinet methods for the preparation of enaminones
- Eanantioselective synthesis of anti-smoking agents
Preparation of Enaminones
Enaminones have long been used as synthetic intermediates in organic synthesis. They can react with electron rich as well as electron deficient compounds. Therefore, the developemnt of methods that can provide access to a broad range of enaminones is valuable. We have developed ruthenium and copper-catalyzed methods that couples diazocarbonyl compounds and thioamides. The reactions are successful with variuos Ru(II) catalysts and copper (I) catalysts.1-3 We are in the process of using this transformation in in conjunction with epoixidation reaction to prepare epoxy enaminones in a one-pot sequence.
The Esehenmoser coupling reaction condenses a thioamide and an alpha-halocarbonyl compound to give enaminones. We have recently developed sonication accelerated version of the Eschenmoser coupling reaction. Reaction conditions have reduced the time for the completion of reaction from days to hours.4 Presently, efforts are underway to further reduce the time of reaction into minutes by manipulating the reaction conditions.
Enantioselective synthesis of anti-smoking agents
Smoking is a leading cause of preventable deaths. An effective and safe smoking cessation agent can drastically reduce this loss. Currently available anti-smoking drugs have limited efficacy and high relapse rates. This is why we are conducting an investigation to find more effective agents.
Research is underway to develop an enantioselective method for the synthesis of compounds that will have the required structural features that can allow them to bind to the a4b2 receptors. These receptors are considered to be responsible for nicotine addiction.
Self-Healing Polymers
In collaboration with Dr. Michael Keller of The University of Tulsa, we are working in the area of self-healing polymers. We prepare compounds with specific funcational groups that are then tested for self-healing propertise.
Electrosynthesis
Electrosynthetic methods tend to be clean, versatile and atom economical. We are initiating projects that will allow regioselective funcationalization of heterocycles via electrosynthesis.
Diels-Alder reactions between electronically mismatched partners
When both the diene and dienophiles are electron-rich, the Diels-Alder reaction requires harsh or specialized conditions/catalysts. We are investigating earth-abundant materials to catalyze such a reaction.
References
- “Ruthenium catalyzed synthesis of enaminones”, N. D. Koduri, H. Scott, B. Hileman, J. D. Cox, M. Coffin, L. Glicksberg and S. R. Hussaini, Org. Lett., 2012, 14, 440–443.
- “Enaminones via ruthenium-catalyzed coupling of thioamides and alpha diazocarbonyl compounds”, N. D. Koduri, Z. Wang, G. Cannell, K. Cooley, T. Tsebaot, K. Miao, M. Nguyen, B. Frohock, M. Castaneda, H. Scott and S. R. Hussaini, The Journal of Organic Chemistry, 2014, 79, 7405–7414.
- “Copper-catalyzed chemoselective cross-coupling reaction of thioamides and alpha dizocarbonyl compounds: Synthesis of enaminones”, A. Pal, N. D. Koduri, Z. Wang, E. L. Quiroz, A. Chong, M. Vuong, N. Rajagopal, M. Nguyen, K. P. Roberts, S. R. Hussaini, Tetrahedron Letters, 2017, 58, 586–589.
- “Acceleration of the Eschenmoser Coupling Reaction by Sonication: Efficient Synthesis of Enaminones”, N. D. Koduri, B. Hileman, J. D. Cox, H. Scott, P. Hoang, A. Robbins, K. Bowers, L. Tsebaot, K. Miao, M. Castaneda, M. Coffin, G. Wei, T. D. W. Claridge, K. P. Roberts and S. R. Hussaini, RSC Advances, 2013, 3, 181–188.