Aqueous Media in the Intramolecular Heck Reaction

Abstract

In the last several years intramolecular variants of the Heck reaction [1] have been developed to produce complex polycyclic structures, as schematically illustrated by conversion of A to D. However, the successful formation of more than one ring in intramolecular Heck reactions of A has depended on substrate structure to prevent β-hydride elimination from intermediate(s) (e.g., B, R ≠ H). For B in which R = H, however, we wondered if aqueous media would favor further alkene insertion over β-hydride elimination in B, either because the alkenebearing chain would be poorly solvated by water (hydrophobic effect [2]) or because water would help to ionize the Pd-X bond. Intriguingly, our preliminary experiments suggest that changing from CH ₃ CN to H ₂ O-CH ₃ CN or H ₂ O-ethanol mixtures, with additives such as LiCl, indeed causes dramatic changes in product distribution for some substrates but not others.