Citation: Changming Li, Hongdan Zhu, Can-Can Bao, Yongjia Lin, Bing-Tao Guan, Qian Peng. Mechanistic insights for Aryl dilithium base enables the acylation of unactivated C_sp3–H[J]. Chinese Chemical Letters, ;2025, 36(9): 110809. doi: 10.1016/j.cclet.2024.110809 shu

Mechanistic insights for Aryl dilithium base enables the acylation of unactivated C_sp3–H

Changming Li ^a ,
Hongdan Zhu ^a ,
Can-Can Bao ^a ,
Yongjia Lin ^a ,
Bing-Tao Guan ^c ,
Qian Peng ^{a, b, *,}

a.
State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China
b.
Haihe Laboratory of Sustainable Chemical Transformation, Tianjin 300192, China
c.
Department of Chemistry, Fudan University, Shanghai 200438, China

^☆

^th

qpeng@nankai.edu.cn

Received Date: 14 October 2024
Revised Date: 18 December 2024
Accepted Date: 26 December 2024
Available Online: 27 December 2024

Figures(7)

Mechanistic studies of the cleavage and transformation of unactivated C_sp3–H bonds are a significant field of chemistry. Overcoming the inherent low acidity of C–H bonds to activate the inert substrates is challenge under mild conditions. And their complex multi-step transformations may also hinder mechanistic understanding. Herein, we perform theoretical calculations and experimental studies to explore the C_sp3–H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA. A synergistic "main and auxiliary" model was revealed involving dual lithium metal by LDA dimers, and the aryl dilithium species as an intermediate base can facilitate C_sp3–H activation. This model not only aids in understanding the acidity of unactivated C_sp3–H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions, but also predicts unusual kinetic isotope effects (KIE) for newly designed 2-(methylthio)naphthalene that are experimentally validated. This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_sp3–H bonds and the development of new functionalities for alkali metal reagents.
- Acylation of unactivated C_sp3–H bonds,
- Mechanistic studies,
- LDA dimers,
- Aryl dilithium base,
- Acidity and nucleophilicity,
- DFT calculations
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Mechanistic insights for Aryl dilithium base enables the acylation of unactivated Csp3–H

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通讯作者: 陈斌, bchen63@163.com

Mechanistic insights for Aryl dilithium base enables the acylation of unactivated C_sp3–H