Selective C–H Functionalization of Bioactive Molecules Via Tunable Electrocatalysis

California Institute Of Technology, Pasadena CA

Investigators

Abstract

Project Summary C?H Functionalization is one of the most powerful methods used by nature and chemists alike to construct bioactive molecules. Both natural and synthetic efforts to catalytically transform C?H bonds into other functionalities have focused on restricting the selectivity of each catalyst to one site on each substrate. This specificity allows for the predictable and strategic application of these methods but does not permit flexibility, requiring a redesign of the catalyst, whether enzyme or small molecule, to achieve a different C?H functionalization outcome. It would be highly desirable to be able to predictably and controllably use a single catalyst for several complementary C?H functionalization reactions, obviating the significant effort needed to retool catalyst selectivity and streamlining the synthesis of bioactive molecules. Recent study in the Gray laboratory has revealed a readily-synthesized iron-nickel cluster to not only be a highly efficient electrocatalyst for the water oxidation reaction but, also, the selective oxidation of C?H bonds. Furthermore, the modulation of applied potential to the system is able to shunt the catalyst between several active states, changing the inherent selectivity of the reaction and permitting tunable selectivity of the C?H functionalization event. Here we propose to develop this means of selectivity into a suite of robust C?H functionalization reactions, specifically C?H oxidation and fluorination, that can be used to enable and improve the development of compounds important to human health.