Research Projects

Nitrogen-containing heterocyclic structures are prevalent in various natural products, bioactive compounds, agrochemicals, and organic functional materials. US FDA-approved drugs data analysis from 2013 to 2023 shows that 82% of new small-molecule drugs contain at least one nitrogen heterocycle, demonstrating the structural impact of nitrogen-containing heterocycles in drug design and development. Nitrogen-centered radicals (NCRs) are highly reactive, promising synthetic intermediates and valuable tools for synthetic chemists for C-N bond formation and building complex nitrogen-containing heterocyclic molecules. Visible-light-mediated single-electron transfer has enabled organic chemists to generate NCRs under mild conditions for synthesizing medicinally relevant nitrogen-containing molecules. Conversely, the generation of aromatic nitrogen-centered radicals (ANHRs) remains challenging due to their instability and difficulty in generation. Unfortunately, there are only very few reports available for the ANHRs generation via visible-light-mediated single-electron transfer. The major drawback of the known methods is that they employ expensive, toxic, and achiral iridium-based photocatalysts and unstable precursor, which limit their applications. Visible light-mediated copper complexes have recently emerged as an appealing alternative to precious metal complexes such as Ir or Ru for functionalization of alkene and arene using NCRs, as they are of a non-toxic nature, Earth-abundant, and inexpensive. Additionally, copper-phenanthroline complexes exhibit excellent photophysical properties, for instance, [*Cu(dap)2]Cl, is a slightly stronger reductant ( -1.4 V) than the most common photo redox catalyst [*Ru(bpy)3]+ (-1.33 V), and [*fac-Ir(dF(CF3)ppy2(dtpbpy)PF6] (-1.33 V), which shows a clear potential that copper-phenanthroline complexes would easily promote the SET for NCRs generation. Unfortunately, there are no reports available for the generation of ANHRs and their application in the functionalization of alkene and arenes using more economical copper complexes. Therefore, we hypothesize that the generation of ANHRs using inexpensive copper catalysts would have wide applications in the synthesis of N-heterocyclic ring-containing molecules in a single step, thus becoming more economical in the drug development process. Additionally, the asymmetric version of the chiral complex will open a new venture in the synthesis of N-heterocyclic drug development. Considering this literature background, the primary objective of the proposed research is to develop a new method for the generation of ANHRs using inexpensive copper catalysts and utilize them for the functionalization of alkene and arenes to synthesize diverse N-heterocyclic drug molecules. Additionally, we aim to develop novel axially chiral copper complexes and utilize them for the enantioselective synthesis of N-heterocyclic molecules and important drugs. To achieve the proposed research, firstly, we will synthesize a stable ANHR precursor, N-heterocyclic pyridinium salts, from commercially available pyrylium salts. Further, a variety of diverse novel 5-membered and benzofused 5-membered N-heterocyclic pyridinium salts will be prepared by simple methods. Next, we will synthesize binaphthyl-based axially chiral phenanthroline ligands for the preparation of chiral copper complexes and study photophysical properties. Further, the synthesized chiral copper-phenanthroline complexes will be used to enantioselectively functionalize the alkene and arene with ANHRs to synthesize diverse N-heterocyclic core-containing chiral molecules. Finally, the developed method will be used for the synthesis of important nitrogen-containing heterocyclic antifungal drugs, such as canazole drugs, and further diverse antibacterial, anti-inflammatory, and other bioactive nitrogen-containing heterocyclic drug molecules will be prepared.