Photoredox cross-electrophile coupling in DNA-encoded chemistry

Biochem Biophys Res Commun. 2020 Dec 3;533(2):201-208. doi: 10.1016/j.bbrc.2020.04.028. Epub 2020 May 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanes / chemical synthesis
  • Alkanes / chemistry*
  • Alkylation
  • Bromides / chemical synthesis
  • Bromides / chemistry*
  • Catalysis
  • Combinatorial Chemistry Techniques
  • DNA / chemical synthesis
  • DNA / chemistry*
  • Hydrocarbons, Aromatic / chemical synthesis
  • Hydrocarbons, Aromatic / chemistry*
  • Iodides / chemical synthesis
  • Iodides / chemistry*
  • Ligands
  • Nickel / chemistry
  • Oxidation-Reduction
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry

Substances

  • Alkanes
  • Bromides
  • Hydrocarbons, Aromatic
  • Iodides
  • Ligands
  • Small Molecule Libraries
  • Nickel
  • DNA