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Updated: Sep 24, 2025

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions
Published on: July 30, 2017
Palladium-Mediated C-N Coupling of DNA-Conjugated (Hetero)aryl Halides with Aliphatic and (Hetero)aromatic Amines
Pratik R Chheda1, Nicholas Simmons1, David P Schuman1
1Discovery Chemistry, Janssen Research & Development, LLC, San Diego, California 92121, United States.
Abstract:
DNA-encoded chemical library (DEL) screens are a powerful hit generation tool in drug discovery, but the diversity of DEL chemical matter is dependent on developing robust reaction conditions that may be used on hundreds to millions of substrate combinations and that are compatible with the platform. Here, we disclose the first report of a general, aqueous, DNA-compatible C-N coupling condition that can now couple aliphatic amines, in addition to (hetero)aromatic amines, with a variety of (hetero)aryl iodides, bromides, and chlorides. The reported BippyPhos-Pd(OAc)2 catalyst system has a wide substrate scope for both coupling partners, is operationally feasible for large scale DEL productions, uses common DEL building block solution stocks, and enables an expansion of DEL-accessible, drug-like chemical space.
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