title: Stereoselective Synthesis of Methylene Oxindoles via Palladium(II)-Catalyzed Intramolecular Cross-Coupling of Carbamoyl Chlorides.
abstract: We report a highly robust, general and stereoselective method for the synthesis of 3-(chloromethylene)oxindoles from alkyne-tethered carbamoyl chlorides using PdCl2(PhCN)2as the catalyst. The transformation involves a stereo- and regioselective chloropalladation of an internal alkyne to generate a nucleophilic vinyl PdIIspecies, which then undergoes an intramolecular cross-coupling with a carbamoyl chloride. The reaction proceeds under mild conditions, is insensitive to the presence of moisture and air, and is readily scalable. The products obtained from this reaction are formed with >95:5 Z:E selectivity in nearly all cases and can be used to access biologically relevant oxindole cores. Through combined experimental and computational studies, we provide insight into stereo- and regioselectivity of the chloropalladation step, as well as the mechanism for the C-C bond forming process. Calculations provide support for a mechanism involving oxidative addition into the carbamoyl chloride bond to generate a high valent PdIVspecies, which then undergoes facile C-C reductive elimination to form the final product. Overall, the transformation constitutes a formal PdII-catalyzed intramolecular alkyne chlorocarbamoylation reaction.
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Le
authors.affiliation: Institute of Organic Chemistry, RWTH Aachen University , Landoltweg 1, 52074 Aachen, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Sperger
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Fu
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Xiao
authors.initials: X
authors.lastname: Hou
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Yong Hwan
authors.initials: YH
authors.lastname: Lim
authors.affiliation: Institute of Organic Chemistry, RWTH Aachen University , Landoltweg 1, 52074 Aachen, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Schoenebeck
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Lautens