Ruthenium-Mediated N-Arylation for DNA-Encoded Libraries

C-N cross coupling reactions are widely employed for the construction of carbon-nitrogen bonds. However, control of chemoselectivity in the presence of the amino functionality in oligonucleotides remains a challenge. Here, we report the development of a new ruthenium reagent that enables the chemoselective N-arylation of amine-DNA conjugates with distinct chemoselectivity when compared to conventional palladium-based C-N bond-forming catalysts. The ruthenium reagent activates commercially available haloarenes in situ via η6 π-arene coordination for subsequent SNAr with the amine. The method is compatible with various commercially available haloarenes and aliphatic amines, and the reaction proceeds under mild conditions.