Robust Suzuki-Miyaura cross-coupling on DNA-linked substrates

The Suzuki-Miyaura cross-coupling is one of the most widely employed reactions in medicinal chemistry. To apply this reaction to DNA-encoded library technology (ELT), an alternative approach in the discovery of small molecule hits and leads, we explored the Suzuki-Miyaura cross-coupling on DNA-linked aryl halides. Pd(PPh3)4 was demonstrated to be an effective catalyst for cross-coupling with on-DNA halide substrates under aqueous conditions. It efficiently catalyzes the coupling of phenyl halides (iodide or bromide) and pyridinyl bromides with various boronic acids/esters, including challenging heterocyclic boronic acids/esters.