Indoles from Alkynes and Aryl Azides. Scope and Theoretical Assessment of Ruthenium Porphyrin-Catalyzed Reactions

A symbiotic experimental/computational study analyzed the Ru(TPP)(NAr)2-catalyzed one-potformation of indoles from alkynes and aryl azides. Thirty different C3-substituted indoleswere synthesizedand best performances, in term of yields and regioselectivities, were observed by reacting ArC?CH alkynes with 3,5-(EWG)2C6H3N3azides, whilst the reaction was less efficient by using electron-rich aryl azides. A DFT analysis describes thereaction mechanism in terms of the energy costs and orbital/electronic evolutions; the limited reactivityof electron-rich azideswas also justified. In summary, PhC?CH alkyne interacts with one NAr imido ligand of Ru(TPP)(NAr)2 to give a residually dangling C(Ph) group which, by coupling with a C(H) unit of the N-aryl substituent, forms a 5+6 bicyclic molecule.Inthe process, two subsequent spin changes allowinverting the conformation of the sp2C(Ph) atom and its consequent electrophilic-like attack tothe aromatic ring. Thebicycleisomerizes to indole viaa two-steps outer sphere H-migration. Eventually, a 'Ru(TPP)(NAr)' mono-imido active catalyst is reformedafter each azide/alkyne reaction.