Electrochemical Annulations of o-Alkynylanilines for Synthesis of 3-Iodoindoles

doi:10.6023/cjoc202112016

Abstract

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

Cite this article

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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Fig. & Tab. 6

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.

Table 1. Optimization of the reaction conditions

Table 2. Substrate scope for the synthesis of 2

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).

Scheme 2. Control experiments

Scheme 3. Proposed reaction mechanism

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