As a result of detailed mechanistic and kinetic studies, we have proposed that PdX2-catalyzed oxidative coupling of o-alkynylanilines 1 with terminal alkynes 2 under aerobic conditions is initiated by aminopalladation of 1 followed by ligand exchange of the resulting s-indolylpalladium(II) complex with 2, reductive elimination and N-demethylation. Side reactions associated with intermediates on the way to 2,3-disubstituted indoles 3 were identified, and the roles of acetate and iodide in channeling the reaction towards the desired product were established. Based on kinetic and spectroscopic studies, the soluble iodide-ligated Pd0 species was proposed to be the resting state of the catalyst and its oxidation to active PdII species was the turnover-limiting step. Catalytic conditions with low loading of Pd(OAc)2 (0.0005 to 0.001 equiv) were subsequently developed.
Jérôme Waser, Mikus Purins, Ashis Kumar Das, Luca Buzzetti
Paul Joseph Dyson, Mingyang Liu, Yelin Hu, Matthias Beller