Photochemical C-H arylation of heteroarenes for DNA-encoded library synthesis

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.

Automated summary

DEL technology is a time- and cost-efficient method for identifying therapeutic candidates in the pharmaceutical industry, but there is still a lack of DNA-compatible reactions that can use building blocks from readily available substructures under mild, dilute, and aqueous conditions for further library diversification.