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  • Asymmetric allylic substitution–isomerization to axially chiral enamides via hydrogen-bonding assisted central-to-axial chirality transfer
Title: Asymmetric allylic substitution–isomerization to axially chiral enamides via 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 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.  more » « less
Award ID(s):
1654122
PAR ID:
10219694
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
Chemical Science
Volume:
11
Issue:
37
ISSN:
2041-6520
Page Range / eLocation ID:
10119 to 10126
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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