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Merging Excited-State Copper Catalysis and Triplet Nitro(hetero)arenes for Direct Synthesis of 2-Aminophenol Derivatives.

Jagrut A ShahArghya BanerjeeUpasana MukherjeeMing-Yu Ngai
Published in: Chem (2023)
Nitro(hetero)arene derivatives are essential commodity chemicals used in various products, such as drugs, polymers, and agrochemicals. In this study, we leverage the excited-state reactivities of copper catalysts and nitro(hetero)arenes, and the Umpolung reactivity of acyl radicals to convert readily available nitro(hetero)arenes directly to valuable 2-aminophenol derivatives, which are important scaffolds in many top-selling pharmaceuticals. This reaction is applicable to a variety of nitro(hetero)arenes, acyl chlorides, and late-stage modifications of complex molecules, making it a useful tool for the discovery of new functional molecules. Mechanistic studies, including radical trapping experiments, Stern Volmer quenching studies, light ON/OFF experiments, and 18 O-labeling studies, suggest a reaction mechanism involving photoexcitation of a copper complex, diradical couplings, and an in-cage contact ion pair (CIP) migration. Our findings offer a streamlined protocol for synthesizing essential pharmacophores from nitro(hetero)arenes while simultaneously advancing knowledge in excited-state and radical chemistry and stimulating new reaction design and development.
Keyphrases
  • case control
  • healthcare
  • small molecule
  • fatty acid
  • high throughput
  • electron transfer
  • water soluble