Enantioconvergent synthesis of axially chiral amides enabled by Pd-catalyzed dynamic kinetic asymmetric aminocarbonylation

Atropisomeric biaryls bearing carbonyl groups have attracted increasing attention due to their prevalence in diverse bioactive molecules and crucial role as efficient organo-catalysts or ligands in asymmetric transformations. However, their preparation often involves tedious multiple steps, and the direct synthesis via asymmetric carbonylation has scarcely been investigated. Herein, we report an efficient palladium-catalyzed enantioconvergent aminocarbonylation of racemic heterobiaryl triflates with amines via dynamic kinetic asymmetric transformation (DyKAT). This protocol features a broad substrate scope and excellent compatibility for rapid construction of axially chiral amides in good to high yields with excellent enantioselectivities. Detailed mechanistic investigations discover that the base can impede the intramolecular hydrogen bond-assisted axis rotation of the products, thus allowing for the success to achieve high enantioselectivity. Moreover, the achieved axially chiral heterobiaryl amides can be directly utilized as N,N,N-pincer ligands in copper-catalyzed enantioselective formation of C(sp<sup>3</sup>)-N and C(sp<sup>3</sup>)-P bonds.

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Publication Details

Journal
Nature Communications
Published
2024-08-23
DOI
https://doi.org/10.1038/s41467-024-51717-8
Citations
27
Primary Topic
Axial and Atropisomeric Chirality Synthesis
Type
article
Field-Weighted Citation Impact
6.75

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article

Enantioconvergent synthesis of axially chiral amides enabled by Pd-catalyzed dynamic kinetic asymmetric aminocarbonylation

Lei Su, Jiawang Liu, Shen Gao
27 citations
Nature Communications
Axial and Atropisomeric Chirality Synthesis
6.75
article

Enantioconvergent synthesis of axially chiral amides enabled by Pd-catalyzed dynamic kinetic asymmetric aminocarbonylation

Lei Su, Jiawang Liu, Shen Gao
article en
27 citations

Abstract

Atropisomeric biaryls bearing carbonyl groups have attracted increasing attention due to their prevalence in diverse bioactive molecules and crucial role as efficient organo-catalysts or ligands in asymmetric transformations. However, their preparation often involves tedious multiple steps, and the direct synthesis via asymmetric carbonylation has scarcely been investigated. Herein, we report an efficient palladium-catalyzed enantioconvergent aminocarbonylation of racemic heterobiaryl triflates with amines via dynamic kinetic asymmetric transformation (DyKAT). This protocol features a broad substrate scope and excellent compatibility for rapid construction of axially chiral amides in good to high yields with excellent enantioselectivities. Detailed mechanistic investigations discover that the base can impede the intramolecular hydrogen bond-assisted axis rotation of the products, thus allowing for the success to achieve high enantioselectivity. Moreover, the achieved axially chiral heterobiaryl amides can be directly utilized as N,N,N-pincer ligands in copper-catalyzed enantioselective formation of C(sp<sup>3</sup>)-N and C(sp<sup>3</sup>)-P bonds.

Nature CommunicationsVol. 15(1)
Shanghai Jiao Tong University (CN), Shanghai Innovative Research Center of Traditional Chinese Medicine (CN)
National Natural Science Foundation of China, Shanghai Rising-Star Program, Fundamental Research Funds for the Central Universities
Openalex Percentile: Top 2%
Axial and Atropisomeric Chirality Synthesis
6.75
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Enantioconvergent synthesis of axially chiral amides enabled by Pd-catalyzed dynamic kinetic asymmetric aminocarbonylation — Lei Su, Jiawang Liu, et al. · Nature Communications (2024) | TGRS Research Map | TGRS