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

作者：Shuai Zhu, Zihao Ye, Mingjie Chen, Lei Wang, Yuzhuo Wang, Kenan Zhang, Wenbo Li, Hanming Ding, Zhiming Li, Junliang Zhang · 发表于：Nature Communications · 年份：2023 · DOI：10.1038/s41467-023-43202-5 · 被引用次数：10 · 研究领域：Catalytic C–H Functionalization Methods、Asymmetric Synthesis and Catalysis、Catalytic Cross-Coupling Reactions

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.