10.1002/anie.201708578
The research focuses on the asymmetric cycloisomerization of o-alkenyl-N-methylanilines to indolines through iridium-catalyzed C(sp3)-H addition to carbon-carbon double bonds. The study establishes a highly enantioselective method for the synthesis of indolines bearing quaternary stereogenic carbon centers at the 3-positions, using an iridium catalyst with a bidentate chiral diphosphine ligand. The experiments involved the reaction of N-methylanilines with o-alkenyl groups in the presence of an iridium catalyst precursor and various chiral phosphorus ligands, with toluene as the solvent at temperatures ranging from 80 to 135°C. The reactants included a range of N-methylaniline derivatives with different substituents on the aniline ring and the double bond. The analyses used to determine the success of the reactions included isolated yields, enantiomeric excess (ee) determined by supercritical fluid chromatography (SFC) with a chiral stationary phase column, and deuterium labeling experiments to probe the reaction mechanism. The study also proposed a reaction mechanism based on the experimental results, which involves rate-determining oxidative addition of the N-methyl C-H bond, followed by intramolecular carboiridation and reductive elimination.