A Sterically Hindered Phosphorus Ligand for Palladium-Catalyzed Sterically Hindered Aryl-Alkyl Coupling Reaction★

doi:10.6023/cjoc202506005

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (9): 3351-3360.DOI: 10.6023/cjoc202506005 Previous Articles Next Articles

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大位阻膦配体在钯催化芳基烷基交叉偶联反应中的应用^★

王楠^a, 汤文军^a^,^b^,^c^,^*()

^a 上海科技大学物质科学与技术学院上海 201210
^b 中国科学院上海有机化学研究所生命过程小分子调控全国重点实验室上海 200032
^c 国科大杭州高等研究院化学和材料科学学院杭州 310024

收稿日期:2025-06-03 修回日期:2025-06-29 发布日期:2025-07-11
基金资助:
国家重点研发计划(2022YFA1503702); 国家重点研发计划(2021YFF0701601); 国家自然科学基金(82188101)

A Sterically Hindered Phosphorus Ligand for Palladium-Catalyzed Sterically Hindered Aryl-Alkyl Coupling Reaction^★

Nan Wang^a, Wenjun Tang^a^,^b^,^c^,^*()

^a School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210
^b State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
^c School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024

Received:2025-06-03 Revised:2025-06-29 Published:2025-07-11
Contact: *E-mail: tangwenjun@sioc.ac.cn
About author:
^★ Academic Papers of the 27^th Annual Meeting of the China Association for Science and Technology.
Supported by:
National Key R&D Program of China(2022YFA1503702); National Key R&D Program of China(2021YFF0701601); National Natural Science Foundation of China(82188101)

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Abstract

The development of sterically hindered aryl-alkyl coupling reactions is of great significance in promoting the advancement of organic synthesis and electronic materials. A conformationally well-defined, sterically hindered, electron-rich monophosphorus ligand ^PAd-AntPhos was designed and synthesized, and its application as a ligand in the palladium-catalyzed Suzuki-Miyaura coupling reaction between sterically hindered aryl halides and cyclic alkylboronic acids were studied. To develop an efficient sterically hindered aryl-alkyl coupling reaction, a more sterically hindered ^PAd-AntPhos based on the structure of AntPhos was designed and synthesized. In the coupling reaction between 2,4,6-triisopropyl bromobenzene and cyclohexylboronic acid, ^PAd-AntPhos has shown excellent reactivity, yielding the target product in 80% yield by screening various reaction conditions including ligands, temperature, and bases. A series of sterically hindered aryl-alkyl coupling products have been obtained in unprecedentedly high yields. Compared to AntPhos, ^PAd-AntPhos has shown good tolerance of steric hindrance.

Key words: palladium, phosphorus ligands, cross-coupling

Cite this article

Nan Wang, Wenjun Tang. A Sterically Hindered Phosphorus Ligand for Palladium-Catalyzed Sterically Hindered Aryl-Alkyl Coupling Reaction^★[J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3351-3360.

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References 23

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Entry^a	Ligands	Base	Conv.^b/%	Yield/% of 7a
1	SPhos	K₃PO₄	0	0	0
2	CPhos	K₃PO₄	100	0	100
3	RuPhos	K₃PO₄	88	0	88
4	BrettPhos	K₃PO₄	100	0	100
5	L1	K₃PO₄	100	65	35
6	L2	K₃PO₄	88	80	8
7^c	L2	K₃PO₄	100	87	13
8^d	L2	K₃PO₄	72	53	19
9	L2	KOH	100	0	100
10	L2	TMSOK	0	0	0
11	L2	^tBuOK	92	64	28

Entry^a	Ligands	Base	Conv.^b/%	Yield/% of 7a
1	SPhos	K₃PO₄	0	0	0
2	CPhos	K₃PO₄	100	0	100
3	RuPhos	K₃PO₄	88	0	88
4	BrettPhos	K₃PO₄	100	0	100
5	L1	K₃PO₄	100	65	35
6	L2	K₃PO₄	88	80	8
7^c	L2	K₃PO₄	100	87	13
8^d	L2	K₃PO₄	72	53	19
9	L2	KOH	100	0	100
10	L2	TMSOK	0	0	0
11	L2	^tBuOK	92	64	28

大位阻膦配体在钯催化芳基烷基交叉偶联反应中的应用^★

A Sterically Hindered Phosphorus Ligand for Palladium-Catalyzed Sterically Hindered Aryl-Alkyl Coupling Reaction^★

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大位阻膦配体在钯催化芳基烷基交叉偶联反应中的应用★

A Sterically Hindered Phosphorus Ligand for Palladium-Catalyzed Sterically Hindered Aryl-Alkyl Coupling Reaction★

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Supporting Info.

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Abstract

Cite this article

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Fig. & Tab. 6

References 23

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大位阻膦配体在钯催化芳基烷基交叉偶联反应中的应用^★

A Sterically Hindered Phosphorus Ligand for Palladium-Catalyzed Sterically Hindered Aryl-Alkyl Coupling Reaction^★