ABSTRACT Transition metal‐catalyzed nucleophilic telomerization of isoprene is an efficient strategy for the construction of monoterpene skeletons, yet its development has been impeded by inherent challenges of chemo‐ and regioselectivity control, especially in reactions with carbon nucleophiles. Herein, we developed a versatile palladium catalysis for the regiodivergent telomerization of isoprene with oxindoles through synergistic control of ligands, solvents, and additives. In the presence of aprotic solvent NMP, we revealed the electron‐rich and less bulky tri(2‐furyl)phosphine (TFP) ligand can facilitate the exclusive formation of tail‐to‐tail geranyl oxindoles, meanwhile the reactivity was severely improved by adding base as additive. On the other hand, a newly designed hemilabile phosphine ligand enables selective access to tail‐to‐head isomer, where the MeOH worked as an irreplaceable solvent choice. Mechanistic experiments and density functional theory (DFT) calculations were conducted, which indicate that protolysis of the η 1 ,η 3 ‐diallyl–Pd(II) complex is speculated to be the rate‐determining step. Apart from oxindoles, this regiodivergent protocol could also be applied to the nucleophilic telomerization of isoprene with a broad scope of amines. Furthermore, the synthetic utility of current synthetic strategy was illustrated by late‐stage alkene isomerization, as well as various derivatizations that effectively expand the structural diversity of monoterpenoids and complement alkaloid frameworks.
Liu et al. (Wed,) studied this question.