title: Methyl ketone oxime esters as nucleophilic coupling partners in Pd-catalyzed C-H alkylation and application in the synthesis of isoquinolines.
abstract: Methyl ketone oxime esters have been found to be excellent coupling partners for C(sp(2))-C(sp(3)) bond formation via Pd-catalyzed aromatic C-H activation. This transformation forms the basis of an approach to regioselectively synthesize substituted isoquinolines via coupling with aryloxime esters. Our mechanistic studies suggested that the reaction proceeded through Pd(II)-catalyzed aromatic C-H activation, tautomerization, and a 1,3-shift of the palladacycle-ligated methyl ketone oxime ester to enable the C-C bond formation by reductive elimination, and intramolecular condensation of an imido-Pd(II) intermediate to form the heterocycle. The aryloxime group not only was used as a directing group for Pd-catalyzed aromatic C-H activation but also functioned as an internal oxidant to allow the reaction to be redox-neutral. Our study illuminated the scope and limitations of this C-H alkylation process, which may serve as the point of departure for developing other C-H functionalization reactions using oxime esters and potentially other carbonyl derivatives as the nucleophilic coupling partners.
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843-3255, United States.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhang
authors.forename: Aijun
authors.initials: A
authors.lastname: Lin
authors.forename: Jiong
authors.initials: J
authors.lastname: Yang