Nitrogen heterocycle represents a ubiquitous skeleton in natural products and drugs. Late-stage C(sp3)-H bond functionalization of N-heterocycles with broad substrate scope remains a challenge and of particular significance to modern chemical synthesis and pharmaceutical chemistry. Here, we demonstrate copper-catalysed late-stage C(sp3)-H functionalizaion of N-heterocycles using commercially available catalysts under mild reaction conditions. We have investigated 8 types of N-heterocycles which are usually found as medicinally important skeletons. The scope and utility of this approach are demonstrated by late-stage C(sp3)-H modification of these heterocycles including a number of pharmaceuticals with a broad range of nucleophiles, e.g. methylation, arylation, azidination, mono-deuteration and glycoconjugation etc. Preliminary mechanistic studies reveal that the reaction undergoes a C-H fluorination process which is followed by a nucleophilic substitution.
Cu-catalyzed C–H late-stage functionalization were employed to modify 5-nitrofuran drugs. Compound 1 and 18 were the most active among all compounds, and the cell cytotoxicity assays were conducted.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.