Synthesis of 2,4,6-Trisubstituted Pyridines via Cobalt-Catalyzed Homocoupling of α,β-Unsaturated Ketone Oxime Esters

doi:10.6023/cjoc202506037

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (10): 3777-3785.DOI: 10.6023/cjoc202506037 Previous Articles Next Articles

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钴催化α,β-不饱和酮肟酯自偶联环化反应合成2,4,6-三取代吡啶

刘占祥^a^,^*(), 洪超^a, 李思源^b, 黄圣儒^a, 张柠霞^a, 冯若昆^b^,^*(), 张玉红^a

^a 浙江大学化学系杭州 310058
^b 绍兴文理学院化学化工学院浙江绍兴 312000

收稿日期:2025-06-30 修回日期:2025-07-27 发布日期:2025-09-03
基金资助:
国家自然科学基金(21672186); 国家自然科学基金(21472165)

Synthesis of 2,4,6-Trisubstituted Pyridines via Cobalt-Catalyzed Homocoupling of α,β-Unsaturated Ketone Oxime Esters

Zhanxiang Liu^a^,^*(), Chao Hong^a, Siyuan Li^b, Shengru Huang^a, Ningxia Zhang^a, Ruokun Feng^b^,^*(), Yuhong Zhang^a

^a Department of Chemistry, Zhejiang University, Hangzhou 310027
^b College of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing, Zhejiang 312000

Received:2025-06-30 Revised:2025-07-27 Published:2025-09-03
Contact: * liuzhanx@zju.edu.cn; fengshenghm86@usx.edu.cn
Supported by:
National Natural Science Foundation of China(21672186); National Natural Science Foundation of China(21472165)

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Abstract

The self-coupling cyclization of α,β-unsaturated ketoxime esters catalyzed by cobalt was developed. This reaction demonstrates excellent substrate compatibility, enabling the participation of various aryl-substituted or heterocyclic-substituted ketoximes to afford the target products in moderate yields. This reaction provides an efficient and convenient synthetic method for the preparation of 2,4,6-trisubstituted pyridine derivatives.

Key words: cobalt catalysis, α,β-unsaturated ketoxime ester, homocoupling cyclization, trisubstituted pyridine

Cite this article

Zhanxiang Liu, Chao Hong, Siyuan Li, Shengru Huang, Ningxia Zhang, Ruokun Feng, Yuhong Zhang. Synthesis of 2,4,6-Trisubstituted Pyridines via Cobalt-Catalyzed Homocoupling of α,β-Unsaturated Ketone Oxime Esters[J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3777-3785.

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Fig. & Tab. 6

References 13

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Entry	Catalyst	Additive	Solvent	Yield^b/%
1	Cp*Co(CO)I₂	Zn(OAc)₂	HFIP	18
2	Cp*Co(CO)I₂	CsOAc	HFIP	26
3	Cp*Co(CO)I₂	NaOAc	HFIP	40
4	Cp*Co(CO)I₂	AgOAc	HFIP	33
5	Cp*Co(CO)I₂	Cu(OAc)₂	HFIP	36
6	*CpCo(CO)I**₂	AgSbF₆	HFIP	65
7	Cp*Co(CO)I₂	AgSbF₆	DCE	22
8	Cp*Co(CO)I₂	AgSbF₆	TFE	Trace
9	Cp*Co(CO)I₂	AgSbF₆	MeOH	Trace
10	Cp*Co(CO)I₂	AgSbF₆	THF	20
11	[Cp*RhCl₂]₂	AgSbF₆	HFIP	53
12	[Ru(p-Cy)Cl₂]₂	AgSbF₆	HFIP	45
13	—	—	HFIP	nd
14	Cp*Co(CO)I₂	—	HFIP	35
15	—	AgSbF₆	HFIP	43

Entry	Catalyst	Additive	Solvent	Yield^b/%
1	Cp*Co(CO)I₂	Zn(OAc)₂	HFIP	18
2	Cp*Co(CO)I₂	CsOAc	HFIP	26
3	Cp*Co(CO)I₂	NaOAc	HFIP	40
4	Cp*Co(CO)I₂	AgOAc	HFIP	33
5	Cp*Co(CO)I₂	Cu(OAc)₂	HFIP	36
6	*CpCo(CO)I**₂	AgSbF₆	HFIP	65
7	Cp*Co(CO)I₂	AgSbF₆	DCE	22
8	Cp*Co(CO)I₂	AgSbF₆	TFE	Trace
9	Cp*Co(CO)I₂	AgSbF₆	MeOH	Trace
10	Cp*Co(CO)I₂	AgSbF₆	THF	20
11	[Cp*RhCl₂]₂	AgSbF₆	HFIP	53
12	[Ru(p-Cy)Cl₂]₂	AgSbF₆	HFIP	45
13	—	—	HFIP	nd
14	Cp*Co(CO)I₂	—	HFIP	35
15	—	AgSbF₆	HFIP	43

钴催化α,β-不饱和酮肟酯自偶联环化反应合成2,4,6-三取代吡啶

Synthesis of 2,4,6-Trisubstituted Pyridines via Cobalt-Catalyzed Homocoupling of α,β-Unsaturated Ketone Oxime Esters

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