可见光诱导活化烯烃的芳基氟烷基化反应

doi:10.6023/cjoc202201011

摘要/Abstract

含氟化合物在生物医药和材料领域有着广泛的应用, 含氟化合物的合成方法学研究有着重要意义. 以fac- Ir(ppy)₃为光催化剂, 可见光诱导下N-芳基-N-(芳基磺酰基)-2-甲基丙烯酰胺经氟烷基自由基加成、芳基迁移、脱砜基历程得到含氟烷基取代α-季碳中心结构的酰胺类化合物, 反应条件温和, 官能团兼容性良好.

关键词: 光催化, 氟烷基化, 芳基迁移, 脱砜基, α-季碳中心, 酰胺

Fluorine-containing compounds have a wide range of applications in the fields of biomedicine and materials, and the development of synthetic methodology for fluorine-containing compounds is very important. Using fac-Ir(ppy)₃ as catalyst, a wide variety of amides containing fluoroalkyl substituted α-quaternary carbon center were prepared with N-aryl-N-(aryl- sulfonyl)-2-methyl acrylamides as starting materials by visible light induced cascade fluoroalkyl radical addition, aryl migration and desulfonylation. The reaction conditions are mild, and possess good functional group compatibility.

Key words: photocatalysis, fluoroalkylation, aryl migration, desulfonylation, α-quaternary carbon center, amide

引用此文

李心灵, 孟卫东, 徐修华, 黄焰根. 可见光诱导活化烯烃的芳基氟烷基化反应[J]. 有机化学, 2022, 42(6): 1820-1830.

Xinling Li, Weidong Meng, Xiuhua Xu, Yan'gen Huang. Visible Light Induced Arylfluoroalkylation of Activated Alkenes[J]. Chinese Journal of Organic Chemistry, 2022, 42(6): 1820-1830.

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图/表 7

图1. 典型的含氟生物活性分子

Figure 1. Typical fluorine-containing bioactive molecules

图式1. 以N-(芳基磺酰)-2-甲基丙烯酰胺为底物构建含季碳中心酰胺

Scheme 1. Construction of amides containing quaternary carbon center with N-(arylsulfonyl)-2-methylacrylamides as substrates

Entry	Catalyst	Base	Solvent	Time/h	Yield ^b/%
1	fac-Ir(ppy)₃	Et₃N	DMSO	12	42
2	fac-Ir(ppy)₃	TMEDA	DMSO	12	49
3	fac-Ir(ppy)₃	DBU	DMSO	12	44
4	fac-Ir(ppy)₃	Cs₂CO₃	DMSO	12	75
5	fac-Ir(ppy)₃	NaHCO₃	DMSO	12	42
6	fac-Ir(ppy)₃	K₂CO₃	DMSO	12	83
7	Ru(bpy)₃Cl₂	K₂CO₃	DMSO	12	42
8	Eosin Y	K₂CO₃	DMSO	12	49
9	Ir(ppy)₂(dtbbpy)PF₆	K₂CO₃	DMSO	12	32
10	Ru(bpy)₃(PF₆)₂	K₂CO₃	DMSO	12	39
11	fac-Ir(ppy)₃	K₂CO₃	MeCN	12	NR
12	fac-Ir(ppy)₃	K₂CO₃	THF	12	NR
13	fac-Ir(ppy)₃	K₂CO₃	DCE	12	15
14	fac-Ir(ppy)₃	K₂CO₃	Acetone	12	35
15	fac-Ir(ppy)₃	K₂CO₃	DMF	12	20
16	fac-Ir(ppy)₃	K₂CO₃	DMSO	10	56
17	fac-Ir(ppy)₃	K₂CO₃	DMSO	14	81

表1. N-芳基-N-(芳基磺酰)-2-甲基丙烯酰胺三氟乙基化的优化a

Table1. Optimization of trifluoroethylation of N-aryl-N-(aryl- sulfonyl)-2-methyl acrylamide

表2. 反应底物拓展a,b

Table 2. Exploration of reaction substrates

图式2. N-(对甲苯基磺酰)-2-甲基丙烯酰胺的二氟乙基化

Scheme 2. Difluoroethylation of N-aryl-N-(p-methylphenyl sulfonyl)-2-methylacrylamides 1 (0.5 mmol), 2b (1.5 mmol), fac-Ir(ppy)3 (2 mol%), K2CO3 (1.0 mmol), DMSO (3.5 mL) were irradiated with a 20 W blue LED at room temperature for time under N2. Isolated yields

图式3. 转化实验

Scheme 3. Transformation experiment

图式4. 可能的反应机理

Scheme 4. Proposed reaction mechanism

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