Pd-catalyzed domino Heck cyclization/cross-coupling of indoles with β-chlorovinyl ketones: synthesis of furan-bearing indolo[2,1-α]isoquinolines with antifungal activity

Abstract

Herein, a palladium-catalyzed cross-coupling cascade cyclization of alkene-tethered indoles and (E)-β-chlorovinyl ketones, providing access to various furan-bearing indolo[2,1-α]isoquinolines, is reported. The reaction enables the rapid construction of one C–O bond and two C–C bonds to form bis-heterocycles. Furthermore, these furan-bearing indolo[2,1-α]isoquinolines exhibited certain antifungal activity in vitro. Notably, bis-heterocycles 3da (EC₅₀ = 16.5014 μg mL⁻¹) against Botryosphaeria dothidea and 3ar (EC₅₀ = 18.2751 μg mL⁻¹) against Rhizoctonia solani were identified to have good inhibitory effects.