Efficient construction of functionalized pyrroloindolines through cascade radical cyclization/intermolecular coupling

By:Jiang, Yonggang ; Liu, Dongxiang; Zhang, Lening ; Qin, Cuirong; Li, Hui; Yang, Haitao ; Walsh, Patrick J. ; Yang, Xiaodong

      Chemical Science

DOI：https://doi.org/10.1039/d3sc05210a

Published：2024-02-07

Abstract

      Pyrroloindolines are important structural units in nature and the pharmaceutical industry, however, most approaches to such structures involve transition-metal or photoredox catalysts. Herein, we describe the first tandem SET/radical cyclization/intermolecular coupling between 2-azaallyl anions and indole acetamides. This method enables the transition-metal-free synthesis of C3a-substituted pyrroloindolines under mild and convenient conditions. The synthetic utility of this transformation is demonstrated by the construction of an array of C3a-methylamine pyrroloindolines with good functional group tolerance and yields. Gram-scale sequential one-pot synthesis and hydrolysis reactions demonstrate the potential synthetic utility and scalability of this approach.

     A novel tandem radical cyclization/intermolecular coupling between 2-azaallyl anions and indole N-aryloxy acetamides is developed, which enables the synthesis of C3a-substituted pyrroloindolines under mild conditions.