Using New Ligands for Palladium Catalyzed Reductive Cyclization to Give Indoles Under Mild Conditions

Brianna R. Sauvé*, Blaine T. McClay and Björn C.G. Söderberg, C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26505

Field (Broad Category): Chemistry (Physical Sciences & Engineering) 

Student’s Major: Forensic Chemistry 

Indole is a naturally existing substructure found within a multitude of fungi, plant, and bacteria. Indoles can also be found as a core in certain medications, like anti-depressants and anti-cancer medications. They are present within regulatory chemicals like serotonin and melatonin. Currently there are about 55 known syntheses of indoles that vary with the type of indole, reagents, starting materials, etc. that are used. The current process of creating indoles for medicine is time consuming and expensive. The main goal of this research is to create new, active catalytic methods that will help simplify the process of reductive cyclization of 2-nitrostyrenes to indoles which in turn would make the process more cost efficient. This includes performing reactions at ambient temperature, utilizing lower catalyst loadings (1%), and at a lower carbon monoxide pressure (1 atm). In comparison to triphenylphosphine that had been used earlier in Dr. Söderberg’s research, the 4,7-dimethoxy-1,10-phenanthroline was shown to be just as effective as a ligand. When using 1% of 4,7-dimethoxy-1,10-phenanthroline and a palladium catalyst, an increase in yield was observed compared to previous methods. It’s indicated that the methoxy groups donate electron density to the binding site of the ligand. This increase in electron density has been suggested to contribute to the increase in efficiency. A new ligand 4,5,6,7-tetramethoxy-1,10-phenanthroline has been proven to be an even more efficient ligand compared to 4,7-dimethoxy-1,10-phenanthroline and has allowed for reactions affording comparable yields but under milder reaction conditions. 

Funding: The National Institutes of Health 

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course