Cr-Catalyzed Reductive Cross-Coupling of Trifluoromethyl Alkenes

doi:10.6023/cjoc202505016

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (9): 3401-3411.DOI: 10.6023/cjoc202505016 Previous Articles Next Articles

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铬催化三氟甲基烯烃的还原交叉偶联

许文, 罗美明^*(), 曾小明^*()

四川大学化学学院成都 610064

收稿日期:2025-05-13 修回日期:2025-05-18 发布日期:2025-05-20
基金资助:
国家自然科学基金(21971168); 国家自然科学基金(22125107)

Cr-Catalyzed Reductive Cross-Coupling of Trifluoromethyl Alkenes

Wen Xu, Meiming Luo^*(), Xiaoming Zeng^*()

College of Chemistry, Sichuan University, Chengdu 610064

Received:2025-05-13 Revised:2025-05-18 Published:2025-05-20
Contact: *E-mail: zengxiaoming@scu.edu.cn; luomm@scu.edu.cn
Supported by:
National Natural Science Foundation of China(21971168); National Natural Science Foundation of China(22125107)

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Abstract

A chromium(II)-catalyzed reduction cross coupling reaction was reported. This reaction utilizes inexpensive and readily available chromium dichloride as a catalyst and 4,4'-di-tert-butyl-bipyridine as a ligand to achieve reduction cross coupling between trifluoromethyl olefins and alkyl bromides under mild conditions, effectively synthesizing difluoroalkene derivatives. This reaction exhibits good substrate universality and is compatible with multiple important functional groups, providing a concise synthetic pathway for constructing conjugated difluoroalkenes containing allyl difluoromethylene structural units. Preliminary mechanistic experiments indicate that alkyl bromides first undergo a reduction process to generate corresponding alkyl radicals, followed by addition to trifluoromethyl olefins. After binding with Cr(II), they undergo a β- fluorine elimination process to generate difluoroalkenes.

Key words: chromium catalysis, gem-difluoroalkene, reductive cross-coupling

Cite this article

Wen Xu, Meiming Luo, Xiaoming Zeng. Cr-Catalyzed Reductive Cross-Coupling of Trifluoromethyl Alkenes[J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3401-3411.

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Fig. & Tab. 7

Scheme 1. Metal-catalyzed coupling of trifluoromethyl alkenes and halodifluoroalkanes

Entry	Deviation from standard conditions	Yield/%
1	None	90 (87)^b
2	Without CrCl₂	nd^c
3	Without Mn	Trace
4	Without dtbpy	40
5	CrCl₃ instead of CrCl₂	49
6	Zn instead of Mn	56
7	bpy instead of dtbpy	36
8	dmdpy instead of dtbpy	37
9	dmobpy instead of dtbpy	58
10	THF instead of DMA	54
11	DME instead of DMA	48
12	CH₃CN instead of DMA	18

Table 1. Optimization of reaction conditionsa

Table 2. Scope of bromodifluoroacetate with various trifluoromethyl alkenes

Table 3. Scope of trifluoromethyl alkene with various difluoroalkylating reagents and alkyl halidesa

Scheme 2. Gram-scale reaction and late-stage functionalization

Scheme 3. Preliminary mechanistic studies

Scheme 4. Presumable reaction pathway

References 20

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	(常哲, 王佳鑫, 陆熹, 傅尧, 有机化学, 2022, 42, 147.) doi: 10.6023/cjoc202108006

铬催化三氟甲基烯烃的还原交叉偶联

Cr-Catalyzed Reductive Cross-Coupling of Trifluoromethyl Alkenes

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