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A Radical Approach for Asymmetric α-C-H Addition of N -Sulfonyl Benzylamines to Aldehydes.

Hui HuZhaoxin ShiXiaochong GuoFeng-Hua ZhangZhaobin Wang
Published in: Journal of the American Chemical Society (2024)
Efficient synthesis of enantioenriched amines is of great importance due to their significant synthetic and biological applications. Photoredox-mediated asymmetric α -amino C(sp 3 )-H functionalization offers an atom-economical and sustainable approach to access chiral amines. However, the development of analogous reactions is in its early stages, generally affording chiral amines with a single stereocenter. Herein, we present a novel synergistic triple-catalysis approach for the asymmetric α -C-H addition of readily available N -sulfonyl amines to aldehydes under mild conditions. This method allows for the efficient synthesis of a diverse array of valuable β -amino alcohols bearing vicinal stereocenters. Unlike previous reports, our protocol employs a radical approach using earth-abundant Cr catalysis. Quinuclidine plays a dual role by facilitating highly selective hydrogen-atom transfer to generate α -amino radicals and promoting the dissociation of the Cr-O bond, which is crucial for the overall catalytic cycle as evidenced by control, NMR, and DFT experiments. Preliminary mechanistic studies, including radical trapping, nonlinear effect, Stern-Volmer plot, kinetic isotope effect, and Hammett plot, offer valuable insights into the reaction pathway.
Keyphrases
  • electron transfer
  • solid state
  • visible light
  • high resolution
  • magnetic resonance
  • molecular dynamics
  • ionic liquid
  • capillary electrophoresis
  • high throughput
  • drug delivery
  • molecular docking
  • drug induced