On the Mechanism of the Palladium Catalyzed Intramolecular Pauson-Khand-Type Reaction

Density functional theory calculations and experimental studies have been carried out on the intramolecular Pauson-Khand-Type reaction mediated by a PdCl2-thiourea catalyst, which proceeds under mild reaction conditions and provides a useful alternative to traditional Pauson-Khand reactions. The classical mechanism of the Pauson-Khand reaction involving the alkyne/alkene C-C bond formation as the key step has been found to be energetically unfavorable and is not in line with the experimental observations. A novel reaction mechanism has been proposed for the reaction. The first step involves the cis-halometalation of the alkyne, followed by sequential alkene and carbonyl insertion. The rate-determining fourth step is an intramolecular C-Cl oxidative addition, leading to a Pd-IV intermediate, A C-C bond formation by reductive elimination completes the reaction. The mechanism is in agreement with the key experimental observations including (I) the need of a chloride for catalytic activity and the absence of catalysis with Pd(OAC)(2) alone; (2) the rate acceleration by the addition of LiCl; both with PdCl2 and Pd(OAc)(2) catalysts; and (3) the preferred formation of the traits diastereomer in substituted cases. The cis halometalation and the formation and stability of the Pd-IV intermediate is studied in detail and provides general insights into these novel steps.