Metal-Free, Photoinduced On-DNA Synthesis of β-Hydroxy Sulfides

We present a metal-free photochemical strategy for the synthesis of on-DNA β-hydroxy sulfides, which are essential pharmacophores with limited access via existing DNA-encoded library (DEL) methodologies. This innovative hydrothiolation features a broad substrate scope with both thiols and olefins. Its operational simplicity and excellent DNA compatibility enable the efficient construction of diverse DELs, significantly expanding the accessible chemical space for drug discovery and providing a new tool for identifying novel therapeutics.