Rhodium-Catalyzed C–H Activation of Indoles for the Construction of Spiroindole Scaffolds

Abstract

Spiroindoles are key scaffolds in a large number of natural products, pharmaceuticals and agrochemicals. Selectively C–H activation has emerged as a powerful synthetic approach to streamline the synthesis of substituted spiroindoles. To date, various 2- and 3 indolyl-tethered aza-spiro-centres have been successfully achieved via C−H activation. However, introduction of spiro-containing systems onto the benzenoid core of indole still remains challenging. Herein, we reported a method of Rh(III)-catalyzed selectively C7−H activation/cyclization of indole with maleimide to afford novel spiroindole derivatives, which incorporated both succinimide and spirocycle into indole unit. Gram-scale synthesis demonstrated the utility of this protocol, further modification via click chemistry offered the novel scaffold as a versatile spiro linker.