Asymmetric Allylic Substitution‐Isomerization for the Modular Synthesis of Axially Chiral N ‐Vinylquinazolinones

Axially chiral N ‐substituted quinazolinones are important bioactive molecules, which are presented in many synthetic drugs. However, most strategies toward their atroposelective synthesis are mainly limited to the axially chiral arylquinazolinone frameworks. The development of modular synthetic met...

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Bibliographic Details
Published in:Angewandte Chemie 2023-10, Vol.135 (40)
Main Authors: Zou, Jia‐Yu, Yang, Yu‐Ying, Gu, Jun, Liu, Fei, Ye, Zhiwen, Yi, Wenbin, He, Ying
Format: Article
Language:English
Subjects:
Asymmetry
Catalysis
Chemistry
Isomerization
Quinazolinone
Quinazolinones
Substitutes
Substrates
Synthesis
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Summary:Axially chiral N ‐substituted quinazolinones are important bioactive molecules, which are presented in many synthetic drugs. However, most strategies toward their atroposelective synthesis are mainly limited to the axially chiral arylquinazolinone frameworks. The development of modular synthetic methods to access diverse quinazolinone‐based atropisomers remains scarce and challenging. Herein, we report the regio‐ and atroposelective synthesis of axially chiral N ‐vinylquinazolinones via the strategy of asymmetric allylic substitution‐isomerization. The catalysis system utilized both asymmetric transition‐metal catalysis and organocatalysis to efficiently afford trisubstituted and tetrasubstituted N ‐vinylquinazolinone atropisomers, respectively. With the meticulous design of β‐substituted allylic substrates, both Z ‐ and E ‐tetrasubstituted axially chiral N ‐vinylquinazolinones were obtained in good yields and high enantioselectivities.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202310320