C-N Coupling of DNA-Conjugated (Hetero)aryl Bromides and Chlorides for DNA-Encoded Chemical Library Synthesis
Related Experiment Video
Updated: Dec 29, 2025

Synthesis of Wavelength-shifting DNA Hybridization Probes by Using Photostable Cyanine Dyes
Published on: July 6, 2016
Ying-Chu Chen1, John C Faver1, Angela F Ku1
1Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, United States.
Abstract:
DNA-encoded chemical library (DECL) screens are a rapid and economical tool to identify chemical starting points for drug discovery. As a robust transformation for drug discovery, palladium-catalyzed C-N coupling is a valuable synthetic method for the construction of DECL chemical matter; however, currently disclosed methods have only been demonstrated on DNA-attached (hetero)aromatic iodide and bromide electrophiles. We developed conditions utilizing an N-heterocyclic carbene-palladium catalyst that extends this reaction to the coupling of DNA-conjugated (hetero)aromatic chlorides with (hetero)aromatic and select aliphatic amine nucleophiles. In addition, we evaluated steric and electronic effects within this catalyst series, carried out a large substrate scope study on two representative (hetero)aryl bromides, and applied this newly developed method within the construction of a 63 million-membered DECL.
More Related Videos
Related Concept Videos
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Halogenation of Alkenes
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
Electrophilic 1,2- and 1,4-Addition of X2 to 1,3-Butadiene
Labeling DNA Probes
Radioisotopes, fluorophores, or small molecule binding partners like biotin or digoxigenin, are the most widely used reporter tags for labeling DNA probes. These labels can be attached to the probe DNA molecule via...
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction

