Simplifying Access to Targeted Protein Degraders via Nickel Electrocatalytic Cross‐Coupling

联轴节(管道) 化学 材料科学 冶金
作者
Philipp Neigenfind,Luca Massaro,Áron Péter,Andrew P. Degnan,Megan A. Emmanuel,Martins S. Oderinde,Chi He,David G. Peters,Tamara El-Hayek Ewing,Yu Kawamata,Phil S. Baran
出处
期刊:Angewandte Chemie [Wiley]
标识
DOI:10.1002/anie.202319856
摘要

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 a‐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. 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 a‐bromoglutaramide 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, multistep 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.
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