Double C–H Functionalization of Indoles via Three-Component Reactions/CuCl₂-Catalyzed Aerobic Dehydrogenative Coupling for the Synthesis of Polyfunctional Cyclopenta[b]indoles

A sequential Rh 2 (OAc) 4 -catalyzed multicomponent reaction and CuCl 2 -catalyzed postcyclization process is developed to build polyfunctional cyclopenta[ b ]indoles in good yields with high diastereoselectivities in an atom- and step-economic fashion. The key discovery in this process is the CuCl 2 -catalyzed intramolecular aerobic dehydrogenative Csp 2 –Csp 2 cross-coupling of indole C2 with an enol functionality. Mechanistic studies including X-ray photoelectron spectroscopy analysis suggest that the catalytic cycle involves Cu(II) and Cu(I). This coupling reaction represents a unique example of aerobic Cu-catalyzed direct coupling of indoles with enols under mild conditions.