光激发丰产金属镍催化卤代芳烃与磺酰胺的C(sp2)—N偶联反应

doi:10.6023/cjoc202511014

有机化学 ›› 2026, Vol. 46 ›› Issue (7): 2835-2852.DOI: 10.6023/cjoc202511014 上一篇下一篇

研究论文

光激发丰产金属镍催化卤代芳烃与磺酰胺的C(sp²)—N偶联反应

王力卓, 刘馨忆, 宋戈洋^*(), 石晓莉, 薛东^*()

陕西师范大学化学化工学院应用表面与胶体化学教育部重点实验室西安 710119

收稿日期:2025-11-21 修回日期:2025-12-22 发布日期:2026-02-11
基金资助:
国家自然科学基金(22171174); 国家自然科学基金(22471150); 国家自然科学基金(22402113); 中央高校基本科研业务费(GK202406026); 中央高校基本科研业务费(GK202505023); 中央高校基本科研业务费(GK202505026); 陕西省创新能力支撑计划(2023-CX-TD-28); 陕西省化学与生物基础科学研究(22JHZ0027); 陕西省自然科学基金(2024JC-YBQN-0075); 天然药物及仿生药物国家重点实验室基金(K202437); 及陕西省重点研发计划(2024CY-JJQ-26)

Photoexcitation-Enabled C(sp²)—N Coupling of Aryl Halides with Sulfonamides Catalyzed by Earth-Abundant Nickel

Lizhuo Wang, Xinyi Liu, Geyang Song^*(), Xiaoli Shi, Dong Xue^*()

Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119

Received:2025-11-21 Revised:2025-12-22 Published:2026-02-11
Contact: *E-mail: songgeyang@snnu.edu.cn;xuedong_welcome@snnu.edu.cn
Supported by:
National Natural Science Foundation of China(22171174); National Natural Science Foundation of China(22471150); National Natural Science Foundation of China(22402113); Fundamental Research Funds for the Central Universities(GK202406026); Fundamental Research Funds for the Central Universities(GK202505023); Fundamental Research Funds for the Central Universities(GK202505026); Innovation Capability Support Program of Shaanxi Province(2023-CX-TD-28); Fundamental Science Research Project for Chemistry and Biology of Shaanxi Province(22JHZ0027); Natural Science Foundation of Shaanxi Province(2024JC-YBQN-0075); State Key Laboratory of Natural and Biomimetic Drugs(K202437); Key Research and Development Program of Shaanxi Province(2024CY-JJQ-26)

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摘要/Abstract

磺酰胺类化合物因其丰富的生物活性、独特的反应活性和潜在的药用价值, 在药物化学与合成化学中备受关注. 发展了一种无需外加光敏剂的温和高效的方法, 在390~395 nm LED光照下, 实现了丰产金属镍催化卤代芳烃与磺酰胺类化合物的C(sp²)—N偶联反应. 该方法以易得的丰产金属镍为催化剂, 温和可溶性的有机胺作为碱, 无需外加光敏剂, 具有原料易得、反应条件温和、操作简便、底物适用性及官能团兼容性强等优点, 并可用于生物活性分子的后期修饰. 在克级反应中, 依然能够保持高效的反应产率, 为合成重要的芳基磺酰胺提供了一种可行的替代方案. 机理研究表明, 该反应可能通过Ni(I)-Ni(III)的催化循环过程.

关键词: 光催化, 镍催化, 芳基卤化物, C—N偶联反应

Sulfonamide compounds have attracted considerable attention in medicinal and synthetic chemistry due to their diverse biological activities, distinctive reactivity, and potential pharmaceutical value. A mild and efficient method that requires no external photosensitizer was developed to achieve the C(sp²)—N coupling of aryl halides with sulfonamide compounds under irradiation from 390~395 nm LEDs, catalyzed by an earth-abundant nickel catalyst. That method employs readily available nickel as the catalyst and soluble organic amines as bases, offering advantages such as easily accessible starting materials, mild reaction conditions, simple operation, broad substrate scope, and excellent functional-group tolerance. It can also be applied to late-stage modification of bioactive molecules. Even on the gram scale, the reaction maintains high efficiency and yield, providing a practical alternative route for the synthesis of important aryl sulfonamides. Mechanistic studies suggest that the reaction may proceed through a Ni(I)-Ni(III) catalytic cycle.

Key words: photocatalysis, nickel catalysis, aryl halide, C—N coupling reaction

引用此文

王力卓, 刘馨忆, 宋戈洋, 石晓莉, 薛东. 光激发丰产金属镍催化卤代芳烃与磺酰胺的C(sp²)—N偶联反应[J]. 有机化学, 2026, 46(7): 2835-2852.

Lizhuo Wang, Xinyi Liu, Geyang Song, Xiaoli Shi, Dong Xue. Photoexcitation-Enabled C(sp²)—N Coupling of Aryl Halides with Sulfonamides Catalyzed by Earth-Abundant Nickel[J]. Chinese Journal of Organic Chemistry, 2026, 46(7): 2835-2852.

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图/表 8

图1. 药物分子中N-芳基磺酰胺片段

Figure 1. N-Arylsulfonamideryl fragments in drug molecules

图式1. 传统过渡金属催化合成N-芳基磺酰胺、光氧化还原与镍协同催化的C—N偶联合成N-芳基磺酰胺及光激发丰产金属镍催化卤代芳烃与磺酰胺的C—N偶联反应

Scheme 1. Traditional transition metal-catalyzed synthesis of N-arylsulfonamides, photoredox with nickel catalyzed C—N coupling for synthesis of N-arylsulfonamides, and photoexcited earth-abundant nickel-catalyzed C—N coupling of aryl halides with sulfonamides

Entry	Deviation from the standard conditions	Yield/%
1	Standard conditions	92 (88)^b
2	NiCl₂	67
3	NiI₂	62
4	Ni(OAc)₂	38
5	NiBr₂•dme	79
6	NiBr₂	83
7	NiCl₂•dme	85
8	DABSO	7
9	BTMG	67
10	DIPEA	25
11	DBU	77
12	DMAP	9
13	K₂CO₃	N.R.
14	MeONa	N.R.
15	Blue LEDs (460~465 nm)	21
16	UV (365~370 nm)	N.R.
17	Green LEDs (530~535 nm)	N.R.
18	White LEDs	N.R.
19	Standard conditions, without ligand	13
20	Standard conditions, without Ni(cod)₂	N.R.
21	Standard conditions, without base	N.R.
22	Standard conditions, light, r.t.	N.R.
23	Standard conditions, without light, heat to 80 ℃	N.R.

表1. 反应条件优化a

Table 1. Optimization of reaction conditions

表2. 芳基溴化物的底物扩展a

Table 2. Scope of aryl bromides

表3. 芳基碘化物的底物扩展a

Table 3. Scope of aryl iodides

表4. 磺酰胺的底物扩展a

Table 4. Scope of sulfonamides

图式2. 克级规模和生物活性分子后期官能团化

Scheme 2. Gram-scale and late-stage functionalization of bioactive molecules

图式3. 可能的反应机理

Scheme 3. Possible mechanism

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光激发丰产金属镍催化卤代芳烃与磺酰胺的C(sp²)—N偶联反应

Photoexcitation-Enabled C(sp²)—N Coupling of Aryl Halides with Sulfonamides Catalyzed by Earth-Abundant Nickel

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