Enantioselective Synthesis of γ-Butyrolactones Bearing γ-Quaternary Stereocenters via Nickel-Catalyzed Reductive Coupling of Acrylates with Ketones

γ-Butyrolactones with γ-quaternary stereocenters are essential structural components in numerous natural products with significant biological activities. While chiral organocatalysis has seen considerable advancements, the development of intermolecular strategies using transition-metal catalysis has remained limited. Here, we describe a nickel-catalyzed, enantioselective reductive coupling strategy to synthesize chiral γ-butyrolactones by reacting acrylates with ketones. This method employs a chiral quinoline-oxazoline ligand and uses benzyl alcohol as a reductant, achieving high enantioselectivity under mild conditions. Additionally, preliminary mechanistic studies elucidate the reaction pathway.

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Publication Details

Journal
Organic Letters
Published
2025-07-14
DOI
https://doi.org/10.1021/acs.orglett.5c02403
Citations
3
Primary Topic
Vanadium and Halogenation Chemistry
Type
article
Field-Weighted Citation Impact
1.61
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article

Enantioselective Synthesis of γ-Butyrolactones Bearing γ-Quaternary Stereocenters via Nickel-Catalyzed Reductive Coupling of Acrylates with Ketones

Bin Xuan, Mengying Qian, Li‐Jun Xiao, Qi‐Lin Zhou
3 citations
Organic Letters
Vanadium and Halogenation Chemistry
1.61
article

Enantioselective Synthesis of γ-Butyrolactones Bearing γ-Quaternary Stereocenters via Nickel-Catalyzed Reductive Coupling of Acrylates with Ketones

Bin Xuan, Mengying Qian, Li‐Jun Xiao, Qi‐Lin Zhou
article en
3 citations

Abstract

γ-Butyrolactones with γ-quaternary stereocenters are essential structural components in numerous natural products with significant biological activities. While chiral organocatalysis has seen considerable advancements, the development of intermolecular strategies using transition-metal catalysis has remained limited. Here, we describe a nickel-catalyzed, enantioselective reductive coupling strategy to synthesize chiral γ-butyrolactones by reacting acrylates with ketones. This method employs a chiral quinoline-oxazoline ligand and uses benzyl alcohol as a reductant, achieving high enantioselectivity under mild conditions. Additionally, preliminary mechanistic studies elucidate the reaction pathway.

Organic LettersVol. 27(29)
Nankai University (CN)
Openalex Percentile: Top 16%
Vanadium and Halogenation Chemistry
1.61
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Enantioselective Synthesis of γ-Butyrolactones Bearing γ-Quaternary Stereocenters via Nickel-Catalyzed Reductive Coupling of Acrylates with Ketones — Bin Xuan, Mengying Qian, et al. · Organic Letters (2025) | TGRS Research Map | TGRS