A catalytic manifold that enables photoredox cross-electrophile coupling of alkyl bromides with DNA-tagged aryl iodides in aqueous solution is presented. This metallaphotoredox transformation was aided by the identification of a new pyridyl bis(carboxamidine) ligand, which proved critical to the nickel catalytic cycle. The described C(sp2)-C(sp3) coupling tolerates a wide range of both DNA-tagged aryl iodides as well as alkyl bromides. Importantly, this reaction was optimized for parallel synthesis, which is a paramount prerequisite for the preparation of combinatorial libraries, by using a 96-well plate-compatible blue LED array as the light source. Therefore, this mild and DNA-compatible transformation is well positioned for the construction of DNA-encoded libraries.
Keywords: Alkyl bromides; Cross-electrophile coupling; DNA; Nickel catalysis; Photoredox catalysis.
Copyright © 2020 Elsevier Inc. All rights reserved.