Metal-Catalyzed One-Pot On-DNA Syntheses of Diarylmethane and Thioether Derivatives
Fei Ma, Jie Li, Shuning Zhang, Yuang Gu, Tingting Tan, Wanting Chen, Shuyue Wang, Hongtao Xu, Guang Yang, Richard A. Lerner
Abstract
Metal catalysis, a common approach in conventional organic synthesis, poses a challenge in DEL chemistry due to the vulnerability of DNA fragments and the requirement of aqueous media. Here, we describe a facile one-pot palladium-catalyzed reaction for the formation of C(sp2)–C(sp3) and C(sp3)–S bonds in the presence of DNA encoding. Using 3, 4-dimethoxybenzenesulfonohydrazide (L8) as a bridging reactant, our studies showed that DNA-conjugated benzaldehyde (HP-ArCHO-1), serving as a common precursor, reacted with derivatives of iodine, bromine, trifluoromethanesulfonate, and disulfides in metal-catalyzed one-pot chemical transformation to afford on-DNA diarylmethanes and thioethers. Notably, all reactions displayed wide substrate scopes and moderate to excellent yields under mild reaction conditions. These chemical reactions greatly expand the chemical space of DNA-compatible reactions and the molecular scaffold diversity of DNA-encoded libraries.