Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

摘要

A series of giant tris(heteroaryl)methanes are easily assembled by one-pot three-component synthesis by simple reflux in ethanol without catalyst or additives. Diversely substituted indoles (Ar¹) react with quinoline aldehydes, quinolone aldehydes, chromone aldehydes, and fluorene aldehydes (Ar²CHO) and coumarins (Ar³) in 1:1:1 ratio to form the corresponding tris(heteroaryl)methanes (Ar¹Ar²Ar³)CH along with (Ar¹Ar¹Ar²)CH triads. A series of new 2:1 triads were also synthesized by coupling substituted indoles with Ar²CHO. The coupling reactions could also be carried out in water (at circa 80 °C) but with chemoselectivity favoring (Ar¹Ar¹Ar²)CH over (Ar¹Ar²Ar³)CH. The molecular structure of a representative (Ar¹Ar²Ar³)CH triad was confirmed by X-ray analysis. Model tris(heteroaryl/aryl)methylium salts were generated by reaction with DDQ/HPF6 and studied by NMR and by DFT and GIAO-DFT.