A Radical Approach for Asymmetric α-C-H Addition of N-Sulfonyl Benzylamines to Aldehydes.
J Am Chem Soc
; 146(8): 5316-5323, 2024 Feb 28.
Article
en En
| MEDLINE
| ID: mdl-38364304
ABSTRACT
Efficient synthesis of enantioenriched amines is of great importance due to their significant synthetic and biological applications. Photoredox-mediated asymmetric α-amino C(sp3)-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 ß-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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
J Am Chem Soc
Año:
2024
Tipo del documento:
Article
País de afiliación:
China