title: Synthesis of 3,3-Disubstituted Oxindoles by Palladium-Catalyzed Asymmetric Intramolecular α-Arylation of Amides: Reaction Development and Mechanistic Studies.
abstract: Palladium complexes incorporating chiral N-heterocyclic carbene (NHC) ligands catalyze the asymmetric intramolecular α-arylation of amides producing 3,3-disubstituted oxindoles. Comprehensive DFT studies have been performed to gain insight into the mechanism of this transformation. Oxidative addition is shown to be rate-determining and reductive elimination to be enantioselectivity-determining. The synthesis of seven new NHC ligands is detailed and their performance is compared. One of them, L8, containing a tBu and a 1-naphthyl group at the stereogenic centre, proved superior and was very efficient in the asymmetric synthesis of fifteen new spiro-oxindoles and three azaspiro-oxindoles often in high yields (up to 99 %) and enantioselectivities (up to 97 % ee; ee=enantiomeric excess). Three palladacycle intermediates resulting from the oxidative addition of [Pd(NHC)] into the aryl halide bond were isolated and structurally characterized (X-ray). Using these intermediates as catalysts showed alkene additives to play an important role in increasing turnover number and frequency.
authors.affiliation: Department of Organic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, 1211 Geneva 4 (Switzerland), Fax: (+41) 22-379-3215.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Katayev
authors.forename: Yi-Xia
authors.initials: YX
authors.lastname: Jia
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Dipshikha
authors.initials: D
authors.lastname: Banerjee
authors.forename: Céline
authors.initials: C
authors.lastname: Besnard
authors.forename: Raghavan B
authors.initials: RB
authors.lastname: Sunoj
authors.forename: E Peter
authors.initials: EP
authors.lastname: Kündig
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D002384:Catalysis; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D000078183:Oxindoles; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D000577:Amides; D007211:Indoles; D008024:Ligands; D000078183:Oxindoles; C022960:2-oxindole; C030011:carbene; D010165:Palladium; D008697:Methane
keywords: N‐heterocyclic carbenes; arylation; asymmetric catalysis; oxindoles; palladium