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Multicomponent alkene azidoarylation by anion-mediated dual catalysis.

Ala BunescuYusra AbdelhamidMatthew J Gaunt
Published in: Nature (2021)
Molecules that contain the β-arylethylamine motif have applications in the modulation of pain, treatment of neurological disorders and management of opioid addiction, among others, making it a privileged scaffold in drug discovery1,2. De novo methods for their assembly are reliant on transformations that convert a small class of feedstocks into the target compounds via time-consuming multistep syntheses3-5. Synthetic invention can drive the investigation of the chemical space around this scaffold to further expand its capabilities in biology6-9. Here we report the development of a dual catalysis platform that enables a multicomponent coupling of alkenes, aryl electrophiles and a simple nitrogen nucleophile, providing single-step access to synthetically versatile and functionally diverse β-arylethylamines. Driven by visible light, two discrete copper catalysts orchestrate aryl-radical formation and azido-group transfer, which underpin an alkene azidoarylation process. The process shows broad scope in alkene and aryl components and an azide anion performs a multifaceted role both as a nitrogen source and in mediating the redox-neutral dual catalysis via inner-sphere electron transfer10,11. The synthetic capabilities of this anion-mediated alkene functionalization process are likely to be of use in a variety of pharmaceutically relevant and wider synthetic applications.
Keyphrases
  • visible light
  • electron transfer
  • drug discovery
  • ionic liquid
  • chronic pain
  • pain management
  • tissue engineering
  • high throughput
  • room temperature
  • combination therapy
  • brain injury
  • blood brain barrier