Copper-catalyzed aerobic oxidative radical alkoxycyclization of tryptamines to access 3-alkoxypyrroloindolines.

Wei Wang,Ting Zhong,Zhi-Yao Li,Jun-Rong Song,Wei-Dong Pan,Hai Ren,Qin Chi

doi:10.1039/d1ra02679h

Abstract

We report a copper-catalyzed alkoxycyclization of tryptamine derivatives with O2 as the sole oxidant, leading to a variety of C3a-alkoxypyrroloindolines in good yields with high diastereoselectivities. This reaction involves an interesting double catalytic cycle in which copper-catalyzed carboamination cyclization is favored to form the C-3 radical pyrrolidinoindoline intermediate, then a copper-catalytic radical alkoxylation reaction proceeds smoothly.

Highlights

We report a copper-catalyzed alkoxycyclization of tryptamine derivatives with O2 as the sole oxidant, leading to a variety of C3a-alkoxypyrroloindolines in good yields with high diastereoselectivities
Some remarkable efforts have contributed to the one-step assembly of 3-hydroxyl,[5] acetoxyl,[6] peroxyl[7] and other oxygenated[8] pyrroloindolines through oxidative cyclization of tryptophan substrates
Copper(II)-promoted radical intramolecular carboamination of alkene has proven to be an effective means toward the synthesis of N-fused heterocycles.[10]

Summary

Introduction

We report a copper-catalyzed alkoxycyclization of tryptamine derivatives with O2 as the sole oxidant, leading to a variety of C3a-alkoxypyrroloindolines in good yields with high diastereoselectivities. As direct access to these complex products, the development of C3a-oxygenation/cyclization reactions of tryptamine or tryptophan derivatives has attracted extensive interest from synthetic chemists. We report an oxazoline/copper-catalyzed cascade carboamination alkoxylation of substituted tryptamine under mild eco-friendly O2 oxidation conditions, which facilitate the construction of the 3-

Results

Conclusion