邻炔基苯胺的电化学环化合成3-碘吲哚

doi:10.6023/cjoc202112016

摘要/Abstract

吲哚及其衍生物是一类重要的杂环化合物, 也是多种天然产物和合成药物的骨架分子. 3-碘吲哚在其选择性功能化中充当着重要的中间体. 电化学氧化廉价易得的碘盐, 促使邻炔基苯胺分子内环化, 便捷地合成了一系列3-碘吲哚类化合物, 目标化合物可获得良好至优秀的产率. 该方法条件温和, 官能团适用范围广, 无需额外添加氧化剂和碱, 是一条操作简便、绿色可持续地合成3-碘吲哚类化合物的途径.

关键词: 电化学合成, 环化反应, 3-碘吲哚, 邻炔基苯胺

Indole, as one of the most important nitrogen-containing heterocyclic compound, is found widely in various natural products and synthetic drugs. 3-Iodoindoles play an important role as intermediate in the selective functionalization of indoles. 3-iodoindoles could be conveniently synthesized by electrochemical annulations of o-alkynylanilines with readily available iodide salt. This sustainable electrolysis strategy provides an efficient access to a series of 3-iodoindoles in good to excellent yields under external oxidant-free, base-free conditions and features broad functional group tolerance.

Key words: electrosynthesis, annulation, 3-iodoindoles, o-alkynylanilines

引用此文

徐鹤华, 孟祥太, 郑煜, 罗金岳, 黄申林. 邻炔基苯胺的电化学环化合成3-碘吲哚[J]. 有机化学, 2021, 41(12): 4696-4703.

Hehua Xu, Xiangtai Meng, Yu Zheng, Jinyue Luo, Shenlin Huang. Electrochemical Annulations of o-Alkynylanilines for Synthesis of 3-Iodoindoles[J]. Chinese Journal of Organic Chemistry, 2021, 41(12): 4696-4703.

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图/表 6

图式1. 通过碘基试剂合成3-碘吲哚

Scheme 1. Synthesis of 3-iodoindoles by iodide-based reagents

Entry	Electrode	Electrolyte	Auxiliary electrolyte	Yield^b/%
1	(+)Pt/(–)Pt	TBAI	—	65
2	(+)Pt/(–)Pt	TBAI	LiClO₄	89
3	(+)C/(–)Ni	TBAI	LiClO₄	68
4	(+)C/(–)C	TBAI	LiClO₄	82
5	(+)Pt/(–)Pt	TBAI	KPF₆	94
6	(+)Pt/(–)Pt	NH₄I	KPF₆	17
7	(+)Pt/(–)Pt	KI	KPF₆	73
8	(+)Pt/(–)Pt	Me₄NI	KPF₆	69
9	(+)Pt/(–)Pt	TBAI^c	KPF₆	67
10	(+)Pt/(–)Pt	TBAI^d	KPF₆	92
11^e	(+)Pt/(–)Pt	TBAI	KPF₆	N.d.^f
12^g	(+)Pt/(–)Pt	TBAI	KPF₆	N.d.

表1. 反应条件优化a

Table 1. Optimization of the reaction conditions

表2. 化合物2的底物范围a,b

Table 2. Substrate scope for the synthesis of 2

图1. 循环伏安法

Figure 1. Cyclic voltammetry Cyclic voltammograms using glassy carbon working electrode, platinum wire counter electrode, and Ag/AgCl (in saturated KCl solution) as the reference electrode on CHI600E station at a scan rate of 100 mV/s. Curve a (blank): 2 mmol/L KPF6 in CH3CN/H2O (6 mL, V∶V=5/1). Curve b (blank+TBAI): 75 mmol/L TBAI and 2 mmol/L KPF6 in CH3CN/H2O (6 mL, V∶V=5/1). Curve c (blank+1a): 50 mmol/L 1a and 2 mmol/L KPF6 in CH3CN/H2O (6 mL, V∶V=5/1). Curve d (blank+1a+TBAI): 50 mmol/L 1a, 75 mmol/L TBAI and 2 mmol/L KPF6 in CH3CN/H2O (6 mL, V∶V=5/1).

图式2. 控制实验

Scheme 2. Control experiments

图式3. 可能的反应机理

Scheme 3. Proposed reaction mechanism

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