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.

SUBMITTER: Sun C 

PROVIDER: S-EPMC8162293 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature