A symbiotic experimental/computational study analyzed the Ru(TPP)(NAr)2-catalyzed one-pot formation of indoles from alkynes and aryl azides. Thirty different C3-substituted indoles were synthesized and the best performance, in term of yields and regioselectivities, was observed when reacting ArC≡CH alkynes with 3,5-(EWG)2C6H3N3 azides, whereas the reaction was less efficient when using electron-rich aryl azides. A DFT analysis describes the reaction mechanism in terms of the energy costs and orbital/electronic evolutions; the limited reactivity of electron-rich azides was 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. In the process, two subsequent spin changes allow inverting the conformation of the sp2 C(Ph) atom and its consequent electrophilic-like attack to the aromatic ring. The bicycle isomerizes to indole via a two-step outer sphere H-migration. Eventually, a ′Ru(TPP)(NAr)′ mono-imido active catalyst is reformed after each azide/alkyne reaction.
Indoles from Alkynes and Aryl Azides: Scope and Theoretical Assessment of Ruthenium Porphyrin-Catalyzed Reactions / Intrieri, D.; Carminati, D. M.; Zardi, P.; Damiano, C.; Manca, G.; Gallo, E.; Mealli, C.. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 25:72(2019), pp. 16591-16605. [10.1002/chem.201904224]