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Simplifying Access to Targeted Protein Degraders via Nickel Electrocatalytic Cross-Coupling.

Philipp NeigenfindLuca MassaroÁron PéterAndrew P DegnanMegan A EmmanuelMartins S OderindeChi HeDavid PetersTamara El-Hayek EwingYu KawamataPhil S Baran
Published in: Angewandte Chemie (International ed. in English) (2024)
C-C linked glutarimide-containing structures with direct utility in the preparation of cereblon-based degraders (PROTACs, CELMoDs) can be assessed in a single step from inexpensive, commercial α-bromoglutarimide through a unique Brønsted-acid assisted Ni-electrocatalytic approach. The reaction tolerates a broad array of functional groups that are historically problematic and can be applied to the simplified synthesis of dozens of known compounds that have only been procured through laborious, wasteful, multi-step sequences. The reaction is scalable in both batch and flow and features a trivial procedure wherein the most time-consuming aspect of reaction setup is weighing out the starting materials.
Keyphrases
  • metal organic framework
  • reduced graphene oxide
  • high resolution
  • electron transfer
  • molecularly imprinted
  • binding protein
  • carbon nanotubes
  • single cell
  • high density
  • liquid chromatography