Non-redox metal ion promoted oxidative coupling of indoles with olefins by the palladium(ii) acetate catalyst through dioxygen activation: experimental results with DFT calculations

Abstract

Developing new catalytic technologies through C–H bond activation to synthesize versatile pharmaceuticals has attracted much attention in recent decades. This work introduces a new strategy in catalyst design for Pd(II)-catalyzed C–H bond activation in which non-redox metal ions serving as Lewis acids play significant roles. In the oxidative coupling of indoles with olefins using dioxygen, it was found that Pd(OAc)₂ alone as the catalyst is very sluggish at ambient temperature which provided a low yield of the olefination product, whereas adding non-redox metal ions to Pd(OAc)₂ substantially improves its catalytic efficiency. In particular, it provided bis(indolyl)methane derivatives as the dominant product, a category of pharmacological molecules which could not be synthesized by Pd(II)-catalyzed oxidative coupling previously. Detailed investigations revealed that the reaction proceeds by heterobimetallic Pd(II)/Sc(III)-catalyzed oxidative coupling of an indole with an olefin followed by Sc(III)-catalyzed addition with a second indole molecule. DFT calculations disclosed that the formation of heterobimetallic Pd(II)/Sc(III) species substantially decreases the C–H bond activation energy barrier, and shifts the rate determining step from C–H bond activation of indole to the olefination step. This non-redox metal ion promoted Pd(II)-catalyzed C–H bond activation may offer a new opportunity for catalyst design in organic synthesis, which has not been fully recognized yet.