Copper-Catalyzed Asymmetric Oxidative Desymmetrization of 2-Substituted 1,2,3-Triols
Kosuke Yamamoto, Yu Suganomata, Takumi Inoue, Masami Kuriyama, Yosuke Demizu and Osamu Onomura*
*Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan,
Email: onomura
nagasaki-u.ac.jp
K. Yamamoto, Y. Suganomata, T. Inoue, M. Kuriyama, Y. Demizu, O. Onomura, J. Org. Chem., 2022, 87, 6479-6491.
DOI: 10.1021/acs.joc.2c00398
see article for more reactions
Abstract
A chiral bisoxazoline ligand/copper catalyst system mediates an asymmetric oxidative desymmetrization of readily accessible 2-(hetero)aryl- and alkyl-substituted glycerols with 1,3-dibromo-5,5-dimethylhydantoin and MeOH. The present transformation provides straightforward access toward various glycerate derivatives in good yields with high enantioselectivities.
see article for more examples
Details
The document details a study on the copper-catalyzed asymmetric oxidative
desymmetrization of 2-substituted glycerols using a chiral bisoxazoline ligand/copper
catalyst system with 1,3-dibromo-5,5-dimethylhydantoin and methanol. This method
effectively converts 2-(hetero)aryl- and alkyl-substituted glycerols into
various glycerate derivatives with high yields and enantioselectivities. The
research emphasizes the significance of chiral tert-alcohols in natural
products and pharmaceuticals, highlighting the need for efficient strategies to
prepare enantiomerically enriched glycerol derivatives.
The study involves optimizing reaction conditions, including ligand selection
and reaction parameters, to achieve high efficiency and selectivity. Various
C2-symmetric BOX ligands were tested, with ligand L8 showing the best results,
providing high yields and enantioselectivities. The substrate scope was explored,
demonstrating that different substituted glycerols could be successfully
desymmetrized.
The scalability of the transformation was confirmed through a gram-scale
reaction, maintaining high yield and enantioselectivity. Additionally, the
synthetic utility of the method was demonstrated by converting the optically
active glycerol into a glyceraldehyde derivative. The document includes detailed
experimental procedures, characterization data, and references to previous
related works, showcasing the potential applications of the developed method in
synthetic chemistry.
Key Words
ID: J42-Y2022
