Theoretical Insight into the Palladium-Catalyzed Prenylation and Geranylation of Oxindoles with Isoprene

This work presents a comprehensive mechanistic study of the ligand-controlled palladium-catalyzed prenylation (with C-5 added) and geranylation (with C-10 added) reactions of oxindole with isoprene. The calculated results indicate that the prenylation with the bis-phosphine ligand and geranylation with the monophosphine ligand fundamentally share a common mechanism. This mechanism involves the formation of two crucial species: a eta(3)-allyl-Pd(II) cation and an oxindole carbon anion. Furthermore, the reactions necessitate the assistance of a second oxindole molecule, which serves as a Br & oslash;nsted acid, providing a proton to generate the oxindole nitrogen anion. The oxindole nitrogen anion then acts as a Br & oslash;nsted base, abstracting a C-H proton from another oxindole molecule to form an oxindole carbon anion. These mechanistic details differ significantly from those proposed in the experimental work. The present calculations do not support the presence of the Pd-H species and the eta(3), eta(3)-diallyl-Pd(II) intermediate, which were previously suggested in experiments. The theoretical results rationalize the experimental finding that the bis-phosphine ligand favors the prenylation of oxindole, while the monophosphine ligand enables the geranylation of oxindole.