RESUMEN
One-pot synthesis of tetrahydro-ß-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.
RESUMEN
Diversely substituted, partially saturated benzo[f]isoindole-4-carboxylic acids were synthesized by a new three-component reaction (3CR) starting from cinnamic amines (3-arylallylamines), maleimides, and maleic anhydride. The process consists of N-acylation of the amines by maleic anhydride, intramolecular [4 + 2] cycloaddition in vinylarenes (the IMDAV reaction), and the concluding Alder-ene reaction between Diels-Alder intermediates and maleimides. All of the reaction steps proceed in a highly regio- and stereoselective manner, furnishing five adjacent chiral centers and leading to a single diastereoisomer of the title compound. The efficiency of the transformation is secured by thermal conditions or utilization of soft Lewis acids (Yb(OTf)3) as catalysts. The kinetics and mechanism of the 3CR were studied by using dynamic 19F NMR. Based on the NMR data and density functional theory (DFT) calculations, the IMDAV, not the Alder-ene, reaction is the rate-limiting step of the entire process.
