Intramolecular Pd-catalyzed reactions of indole derivatives

Indole is probably the most ubiquitous heterocycle in nature. Owing to the great structural diversity of biologically or synhetically relevant indoles, this nucleus has become an important skeleton endowed with pharmacological and agrochemical activities.(1) For over a hundred years, synthesis and functionalization of indoles have been a relevant area for synthetic organic chemists. In some cases, specific substitution patterns remain difficult to obtain by standard indole-forming reactions, thus, all the new emerging methodologies are of great interest.(2) Palladium complexes have been used in the synthesis and derivatization of complex organic molecules, including indoles. Within these synthetic protocols, besides more classical Pd(0)-catalyzed reactions, several oxidative reactions based on Pd(II) catalysis have been used for indole functionalization, some of which represent a convenient tool for the direct elaboration of the indole core motif.(3) Undoubtedly, C-H activation/functionalization has received increased attention as an alternative strategy, due to the fact that it offers improved atom and step-economy compared to the traditional cross-coupling-based methods where extra steps are needed for pre-activation of the substrates.(4) Following our interest towards Pd-catalyzed reactions as well as towards the synthesis of complex heteropolycyclic systems, we developed several Pd-catalyzed methodologies applied to variously substituted indole derivatives providing selective access to different heteropolycyclic systems containing the indole skeleton.