Photochemical C-H arylation of heteroarenes for DNA-encoded library synthesis.
Matthias KrumbLisa Marie KammerShorouk O BadirMaría Jesús Cabrera-AfonsoVictoria E WuMinxue HuangAdam CsakaiLisa A MarcaurelleGary A MolanderPublished in: Chemical science (2021)
DNA-encoded library (DEL) technology has emerged as a time- and cost-efficient technique for the identification of therapeutic candidates in the pharmaceutical industry. Although several reaction classes have been successfully validated in DEL environments, there remains a paucity of DNA-compatible reactions that harness building blocks (BBs) from readily available substructures bearing multifunctional handles for further library diversification under mild, dilute, and aqueous conditions. In this study, the direct C-H carbofunctionalization of medicinally-relevant heteroarenes can be accomplished via the photoreduction of DNA-conjugated (hetero)aryl halides to deliver reactive aryl radical intermediates in a regulated fashion within minutes of blue light illumination. A broad array of electron-rich and electron-poor heteroarene scaffolds undergo transformation in the presence of sensitive functional groups.