One-Pot Reaction Sequence: N-Acylation/Pictet–Spengler Reaction/Intramolecular [4 + 2] Cycloaddition/Aromatization in the Synthesis of β-Carboline Alkaloid Analogues

Abstract

One-pot synthesis of tetrahydro-β-carbolines, fused with an isoindole core, was proposed starting from maleic anhydride and azomethines easily available from tryptamines and 3-(hetaryl)­acroleins. This sequence includes four key steps: an acylation of the aldimine with maleic anhydride, a Pictet–Spengler cyclization, an intramolecular Diels–Alder reaction, and a concluding [1,3]-H shift. As a result, six- or seven-nuclear alkaloid-like heterocyclic systems, containing a benzo­[1,2]­indolizino­[8,7-b]­indole fragment annulated with furan, thiophene, or pyrrole, are formed in a diastereoselective manner.