Mechanistic Studies of a Palladium-Catalyzed Intramolecular Hydroamination of Unactivated Alkenes: Protonolysis of a Stable Palladium Alkyl Complex Is the Turnover-Limiting Step

Mechanistic studies of the intramolecular hydroamination of unactivated aminoalkenes catalyzed
by a dicationic [bis(diphenylphosphinomethyl)pyridine]palladium complex highlight the important role that
protonolysis plays in this reaction. Coordination of the aminoalkene substrate to this complex activates the
alkene toward intramolecular nucleophilic attack to form a dicationic palladium alkyl complex (6). A stable
monocationic palladium alkyl complex (7) was isolated by in situ deprotonation of 6 with mild base, and its
structure was confirmed by X-ray crystallography. Complex 7 reacted rapidly with a variety of strong acids
to undergo protonolysis, resulting in formation of hydroamination product 3 and regenerating the active
catalyst. Evidence that formation of the palladium alkyl complex is reversible under the catalytic conditions
was obtained from observation of the protonolysis at low temperature. During the course of all catalytic
reactions, the resting state of the catalyst was palladium alkyl complex 7, indicating that protonolysis of the
Pd−C bond was the turnover-limiting step. Kinetic studies reveal an unusual inverse dependence of the
reaction rate on the concentration of the aminoalkene substrate. This effect can be accurately explained
by a model in which the carbamate protecting group of the aminoalkene acts as a Brønsted base to remove
free protons from the catalytic cycle and thereby inhibits the turnover-limiting protonolysis step. Formation
of a 2:1 complex (12) between the carbamate and the proton is most consistent with the kinetic data.