Intercepted-Knoevenagel condensation for the synthesis of unsymmetrical fused-tricyclic 4 H-pyrans

Tetrahedron. 2019 Oct 25;75(43):130606. doi: 10.1016/j.tet.2019.130606. Epub 2019 Sep 17.

Abstract

4H-Pyrans (4H-Pys) and 1,4-dihydropyridines (1,4-DHPs) are important classes of heterocyclic scaffolds in medicinal chemistry. Herein, an indium(III)-catalyzed one-pot domino reaction for the synthesis of highly functionalized 4H-Pys, and a model of 1,4-DHP is reported. This alternative approach to the challenging Hantzsch 4-component reaction enables the synthesis of fused-tricyclic heterocycles, and the mechanistic studies underline the importance of an intercepted-Knoevenagel adduct to achieve higher chemoselectivity towards these types of unsymmetrical heterocycles.

Keywords: 4H-pyrans; Domino reaction; Hydrogen-bond network; Intercepted-Knoevenagel condensation; Multicomponent reaction.