Mechanistic study on the side arm effect in a palladium/Xu-Phos-catalyzed enantioselective alkoxyalkenylation of γ-hydroxyalkenes

Recently, the asymmetric bifunctionalization of alkenes has received much attention. However, the development of enantioselective alkoxyalkenylation has posed a considerable challenge and has lagged largely behind. Herein, we report a new palladium-catalyzed enantioselective alkoxyalkenylation reaction, using a range of primary, secondary, and tertiary γ-hydroxy-alkenes with alkenyl halides. By employing newly identified Xu-Phos ( Xu8 and Xu9 ) with a suitable side-arm adjacent to the PCy 2 motif, a series of allyl-substituted tetrahydrofurans were obtained in good yields with up to 95% ee . Besides ( E )-alkenyl halides, ( Z )-alkenyl halide was also examined and provided the corresponding ( Z )-product as a single diastereomer, supporting a stereospecific oxidative addition and reductive elimination step. Moreover, deuterium labeling and VCD experiments were employed to determine a cis -oxypalladation mechanism. DFT calculations helped us gain deeper insight into the side-arm effect on the chiral ligand. Finally, the practicability of this method is further demonstrated through a gram-scale synthesis and versatile transformations of the products. Recently, the asymmetric bifunctionalization of alkenes has received much attention but the development of enantioselective alkoxyalkenylation has posed a considerable challenge and has lagged largely behind. Here, the authors report a palladium-catalyzed enantioselective alkoxyalkenylation reaction, using a range of primary, secondary, and tertiary γ-hydroxyalkenes with alkenyl halides.