Asymmetric allylic substitution-isomerization to axially chiral enamides hydrogen-bonding assisted central-to-axial chirality transfer

Axially chiral enamides bearing a N-C axis have been recently studied and were proposed to be valuable chiral building blocks, but a stereoselective synthesis has not been achieved. Here, we report the first enantioselective synthesis of axially chiral enamides via a highly efficient, catalytic appr...

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Published in:Chemical science (Cambridge) 2020-09, Vol.11 (37), p.1119-1126
Main Authors: Sun, Chao, Qi, Xiaotian, Min, Xiao-Long, Bai, Xue-Dan, Liu, Peng, He, Ying
Format: Article
Language:English
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Summary:Axially chiral enamides bearing a N-C axis have been recently studied and were proposed to be valuable chiral building blocks, but a stereoselective synthesis has not been achieved. Here, we report the first enantioselective synthesis of axially chiral enamides via a highly efficient, catalytic approach. In this approach, C(sp 2 )-N bond formation is achieved through an iridium-catalyzed asymmetric allylation, and then in situ isomerization of the initial products through an organic base promoted 1,3-H transfer, leading to the enamide products with excellent central-to-axial transfer of chirality. Computational and experimental studies revealed that the 1,3-H transfer occurs via a stepwise deprotonation/re-protonation pathway with a chiral ion-pair intermediate. Hydrogen bonding interactions with the enamide carbonyl play a significant role in promoting both the reactivity and stereospecificity of the stepwise 1,3-H transfer. The mild and operationally simple formal N -vinylation reaction delivered a series of configurationally stable axially chiral enamides with good to excellent yields and enantioselectivities. Axially chiral enamides bearing a N-C axis have been recently studied and were proposed to be valuable chiral building blocks, but a stereoselective synthesis has not been achieved.
ISSN:2041-6520
2041-6539
DOI:10.1039/d0sc02828b