Cu-Catalyzed Oxidative 3-Amination of Indoles via Formation of Indolyl(aryl)iodonium Imides Using o-Substituted (Diacetoxyiodo)arene as a High-Performance Hypervalent Iodine Compound.

Kazuhiro Watanabe,Katsuhiko Moriyama

doi:10.3390/molecules24061147

Abstract

An oxidative 3-amination of indole derivatives using hypervalent iodine(III) and bissulfonimides, which proceeds via the formation of indolyl(aryl)iodonium imides, was developed. This reaction was followed by an indole-selective copper-catalyzed oxidative C–N coupling reaction to obtain 3-amino indole derivatives as single regioisomers. o-Alkoxy(diacetoxyiodo)arenes showed higher reactivity in the reaction than o-alkyl(diacetoxyiodo)arenes, efficiently promoting the formation of indolyl(aryl)iodonium imides in the first step.

Highlights

The direct installation of an amino group into an indole skeleton is a very important strategy to generate amino indole derivatives, which are key building blocks for indole-based natural products and biologically active compounds [1,2,3,4,5,6]
Compound that promotes the formation of indolyl(aryl)iodonium imides
This reaction was followed by a copper-catalyzed oxidative C–N coupling reaction to obtain the 3-amino indole derivatives regioselectively

Summary

Introduction

The direct installation of an amino group into an indole skeleton is a very important strategy to generate amino indole derivatives, which are key building blocks for indole-based natural products and biologically active compounds [1,2,3,4,5,6]. I–N bonding hypervalent iodine compounds, from N-electron-withdrawing group protected indoles, bissulfonimides, and (diacetoxyiodo)arenes [18,19], and to achieve the dual functionalization of indoles via halo-amination with halogen reagents using the indolyl(aryl)iodonium imides [18,20]. We report reportherein a 3-selective coupling reaction of N-electron-withdrawing group indoles with various using hypervalent iodine compounds C–N coupling reaction of indoles withofbissulfonimides via the formation of would promote the copper-catalyzed indoles with bissulfonimides via the indolyl(aryl)iodonium imides. 3-amino indole derivatives method, formation indolyl(aryl)iodonium imides should proceed effectively than indole using thisthe method, the of formation of indolyl(aryl)iodonium imides should proceedother effectively other selectivity the C–N coupling reaction of indolyl(aryl)iodonium imides. ArI(N(SO2R2)2)2), which is generated in situ from the reaction of (diacetoxyiodo)arene with bissulfonimides, would suppress the formation of indolyl(aryl)iodonium imides.

Discussion

Copper-catalyzed

General Procedure

General Procedure for 3-Amination of Indoles 1

Conclusions