Citation: Xin-Han Wang, Ying Huang, Chun-Lin Zhang, Song Ye. γ-C(sp³)-H acylation of aliphatic amines enabled by cooperative photoredox NHC/Pd catalysis[J]. Chinese Chemical Letters, ;2026, 37(5): 111484. doi: 10.1016/j.cclet.2025.111484 shu

γ-C(sp³)-H acylation of aliphatic amines enabled by cooperative photoredox NHC/Pd catalysis

Xin-Han Wang ^{a, b} ,
Ying Huang ^{a, b} ,
Chun-Lin Zhang ^{a, *,} ,
Song Ye ^{a, b, *,}

a.
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
b.
University of Chinese Academy of Sciences, Beijing 100049, China

zhangchunlin@iccas.ac.cn

songye@iccas.ac.cn

Received Date: 14 January 2025
Revised Date: 12 June 2025
Accepted Date: 17 June 2025
Available Online: 18 June 2025

Figures(6)

The site-selective C(sp³)-H functionalization is of great importance in synthetic chemistry. However, γ-amino C(sp³)-H functionalization of aliphatic amines remains challenging. Herein, we develop an efficient γ-C(sp³)-H acylation of aliphatic amines by cooperative photoredox NHC/Pd catalysis. The process entails the following key steps: (ⅰ) photoinduced palladium-promoted formation of aryl radical, (ⅰ) generation of transient γ-amino alkyl radical through aryl radical-mediated 1,7-HAT, (ⅲ) single-electron oxidation of Breslow enolate intermediate to persistent ketyl radical, and (ⅳ) radical/radical coupling of γ-amino alkyl radical with ketyl radical. The synthetic utility of this γ-amino C(sp³)-H acylation is illustrated by the conversion of readily available aliphatic amines to a diverse collection of γ-aminoketones, which serve as versatile building blocks to enable the synthesis of pyrrolines of interest in medicinal chemistry. The radical mechanism is supported by the results of various control experiments, in situ EPR analysis, radical trapping experiment, and isotopic labeling studies.
- N-Heterocyclic carbene,
- Palladium,
- Cooperative catalysis,
- C(sp³)-H acylation,
- Aliphatic amine
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γ-C(sp3)-H acylation of aliphatic amines enabled by cooperative photoredox NHC/Pd catalysis

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通讯作者: 陈斌, bchen63@163.com

γ-C(sp³)-H acylation of aliphatic amines enabled by cooperative photoredox NHC/Pd catalysis