Site-selective C-5 trifluoromethylation of N-8-quinolinyl benzamide using a nickel catalyst

Carter Boger*, Shannen Lorraine, and Jessica Hoover
C. Eugene Bennet Department of Chemistry, West Virginia University, Morgantown, WV 26505

Presentation No.: 100

Assigned Category (Presentation Format): Physical Sciences (Poster Presentations)

Student’s Major: Biochemistry

Trifluoromethyl (-CF3) groups are one of the most utilized functional groups in medical and agricultural chemistry due to their ability to increase lipophilicity and decrease metabolic breakdown of organic molecules. However, its addition typically requires molecules to be pre-functionalized with a leaving group, which increases cost, chemical waste, and complexity during chemical synthesis. Direct trifluoromethylation is possible by combining metal catalysts with directing groups such as N-8-quinolinyl benzamide, but usually at the cost of reaction specificity, resulting in unwanted biproducts. In addition, the quinoline backbone itself is difficult to functionalize using this method. This research explores a highly selective nickel-catalyzed trifluoromethyl functionalization of N-8-quinolinyl benzamide in the carbon-5 position, which has yet to be reported in the literature. Our current methodology focuses on optimization of reaction conditions including catalysts, bases, solvents, and oxidants required to synthesize 5-(trifluoromethyl)-8-quinolinyl benzamide. In the future, this research may allow for the development of new cross-coupling reactions that can be used to functionalize heteroarenes with a broad scope of substrates.

Funding: NIH grant R15 GM126514-01

Program/mechanism supporting research/creative efforts: WVU's SURE program (Rita Rio & Michelle Richards-Babb)