DNA-Encoded Libraries: Aryl Fluorosulfonates as Versatile Electrophiles Enabling Facile On-DNA Suzuki, Sonogashira, and Buchwald Reactions

Hongtao Xu; Fei Ma; Nan Wang; Wei Hou; Huan Xiong; Fengping Lu; Jie Li; Shuyue Wang; Peixiang Ma; Guang Yang; Richard A Lerner

doi:10.1002/advs.201901551

DNA-Encoded Libraries: Aryl Fluorosulfonates as Versatile Electrophiles Enabling Facile On-DNA Suzuki, Sonogashira, and Buchwald Reactions

Adv Sci (Weinh). 2019 Sep 30;6(23):1901551. doi: 10.1002/advs.201901551. eCollection 2019 Dec.

Authors

Hongtao Xu¹, Fei Ma¹, Nan Wang¹, Wei Hou², Huan Xiong¹, Fengping Lu¹, Jie Li¹, Shuyue Wang¹, Peixiang Ma¹, Guang Yang¹, Richard A Lerner³

Affiliations

¹ Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech University Shanghai 201210 China.
² College of Pharmaceutical Science and Institute of Drug Development & Chemical Biology (IDD & CB) Zhejiang University of Technology Hangzhou 310014 China.
³ Department of Chemistry Scripps Research Institute La Jolla CA 92037 USA.

Abstract

Using (hetero)aryl fluorosulfonates as versatile electrophiles, facile on-DNA cross-coupling reactions of Suzuki, Sonogashira, and Buchwald are reported here. Notably, all of these reactions show excellent functional group tolerance, mild reaction conditions (relative low temperature and open to air), rich heterocyclic coupling partners, and more importantly, DNA-compatibility. Thus, these new reactions based on efficient formation of C(sp²)-C(sp²), C(sp²)-C(sp), and C(sp²)-N bonds are highly amenable to synthesis of DNA-encoded libraries with great molecular diversity.

Keywords: Buchwald; DNA‐encoded library; Sonogashira; Suzuki; fluorosulfonate; palladium.