Fei Ma; Jie Li; Shuning Zhang; Yuang Gu; Tingting Tan; Wanting Chen; Shuyue Wang; Hongtao Xu; Guang Yang; Richard A. Lerner
ACS Catal., 2022, 12(3), 1639-1649
https://doi.org/10.1021/acscatal.1c05338

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.