Part I: Probing the limits of C–H functionalization methods with secondary metabolites: Synthesis of a benzo-fused indoxamycin core. Part II: Uranyl cation as a photocatalyst for Csp3–H fluorination.

Abstract

Methods for functionalizing carbon-hydrogen bonds are featured in a new synthesis of the tricyclic core architecture that characterizes the indoxamycin family of secondary metabolites. A unique collaboration between four laboratories has engendered a design for synthesis featuring two sequential C–H functionalization reactions: a diastereoselective dirhodium-carbene insertion followed by an ester-directed, oxidative Heck cyclization to rapidly assemble the congested tricyclic core of the indoxamycins. This project exemplifies how multi-laboratory collaborations can foster conceptually novel approaches to challenging problems in chemical synthesis.

The fluorination of unactivated Csp3–H bonds remains a highly desirable and challenging transformation for pharmaceutical, agricultural, imaging, and materials scientists. Previous methods to accomplish this transformation have used bench-stable fluorine atom sources; however, many still rely on the use of UV-active photocatalysts for the requisite high-energy hydrogen atom abstraction event. Uranyl nitrate hexahydrate as a convenient, hydrogen atom abstraction catalyst that can fluorinate certain alkanes, in some cases with high efficiency and selectivity. This earth-abundant photocatalyst functions under visible light irradiation and exhibits remarkable selectivity in comparison to the previously-reported, UV-active species.