Issue 37, 2020

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

Abstract

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(sp2)–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.

Graphical abstract: Asymmetric allylic substitution–isomerization to axially chiral enamides via hydrogen-bonding assisted central-to-axial chirality transfer

Supplementary files

Article information

Article type
Edge Article
Submitted
18 May 2020
Accepted
06 Sep 2020
First published
07 Sep 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2020,11, 10119-10126

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

C. Sun, X. Qi, X. Min, X. Bai, P. Liu and Y. He, Chem. Sci., 2020, 11, 10119 DOI: 10.1039/D0SC02828B

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