Mechanistic study on the side arm effect in a palladium/Xu-Phos-catalyzed enantioselective alkoxyalkenylation of γ-hydroxyalkenes
Shuai Zhu, Zihao Ye, Mingjie Chen, Lei Wang, Yuzhuo Wang, Kenan Zhang, Wenbo Li, Hanming Ding, Zhiming Li, Junliang Zhang
Abstract
Abstract 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.