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

INSUASTY, BRAULIO; ZHAO, CHUNQING; BUNGE, SCOTT D.; ABONIA, RODRIGO; QUIROGA, JAIRO; BOROSKY, GABRIELA L.; GUTIÉRREZ, LUISA F.; LAALI, KENNETH K.; HORWITZ, SAMANTHA M.

BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY

BEILSTEIN-INSTITUT

Año: 2019 vol. 15 p. 642 - 654

1860-5397

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 (Ar 1 ) react with quinoline aldehydes, quinolone aldehydes, chromone aldehydes, and fluorene aldehydes (Ar 2 CHO) and coumarins (Ar 3 ) in 1:1:1 ratio to form the corresponding tris(heteroaryl)methanes (Ar 1 Ar 2 Ar 3 )CH along with (Ar 1 Ar 1 Ar 2 )CH triads. A series of new 2:1 triads were also synthesized by coupling substituted indoles with Ar 2 CHO. The coupling reactions could also be carried out in water (at circa 80 °C) but with chemoselectivity favoring (Ar 1 Ar 1 Ar 2 )CH over (Ar 1 Ar 2 Ar 3 )CH. The molecular structure of a representative (Ar 1 Ar 2 Ar 3 )CH triad was confirmed by X-ray analysis. Model tris(heteroaryl/aryl)methylium salts were generated by reaction with DDQ/HPF 6 and studied by NMR and by DFT and GIAO-DFT.