title: Mechanistic study on the palladium(II)-catalyzed synthesis of 2,3-disubstituted indoles under aerobic conditions: anion effects and the development of a low-catalyst-loading process.
abstract: 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 σ-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 Pd(0) species was proposed to be the resting state of the catalyst and its oxidation to active Pd(II) species was the turnover-limiting step. Catalytic conditions with low loading of Pd(OAc)2 (0.0005 to 0.001 equiv) were subsequently developed.
authors.affiliation: Laboratory of Synthesis and Natural Products, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN BCH 5304, 1015 Lausanne (Switzerland), Fax: (+41) 21-693-97-40.
authors.forename: Bo
authors.initials: B
authors.lastname: Yao
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Jieping
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000838:Anions; D002384:Catalysis; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*
chemical_list: D000838:Anions; D007211:Indoles; D010165:Palladium
keywords: aerobic; anion effect; indoles; low catalyst loading; palladium; reaction mechanisms