Radical-Based Late Stage C–H Functionalization of Heteroaromatics in Drug Discovery

Abstract

The development of the radical-based C–H functionalization of heteroaromatics is in demand, since it can directly introduce medicinally important functionalities (Me, CF3, etc.) to druggable compounds during the late stage of synthesis. Classical methods using alkyl carboxylic acids and alkyl halides as a radical precursor have been reported, however, they are still under development regarding the reaction conditions and the substrate scope. These drawbacks inspired us to invent two radical-based C–H functionalization methods. The first topic covers the C–H alkylation and arylation using boronic acids as a radical precursor, while the latter covers the C–H alkylation using sulfinate salts as a radical precursor. Additionally, new reagents for the C–H functionalization were invented during the course of these studies. Under ambient conditions using inexpensive reagents and simple procedures, our methods can supply a rapid access to complex molecules which are difficult to prepare by traditional methods. Due to these features and the growing demand for the late stage functionalization in drug discovery, our strategies have already been utilized by Pfizer and Sigma-Aldrich.