One-step synthesis of azepino[3,4-b]indoles by cooperative aza-[4 + 3] cycloaddition from readily available feedstocks†
Abstract
Azepino[3,4-b]indoles are a family of molecules with pharmaceutical significance that contain an aza-seven-membered ring system. However, synthetic approaches to this scaffold are limited and typically require multiple steps. Here, we demonstrate the feasibility of obtaining azepino[3,4-b]indoles by one-step synthesis from a four-component reaction system comprising readily available starting materials, i.e., an amino acid, an indole, and an aniline. This transformation affords a diverse range of azepino[3,4-b]indoles in a highly efficient manner. We propose that the self-sorting integration of two kinetically unstable intermediates, an indol-3-yl cation and an N-arylimine, is key to realizing the cooperative aza-[4 + 3] cycloaddition.