Zhu Shuai, Ye Zihao, Chen Ming-Jie, Wang Lei, Wang Yu-Zhuo, Zhang Ke-Nan, Li Wen-Bo, Ding Han-Ming, Li Zhiming, Zhang Junliang
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663 N. Zhongshan Road, Shanghai, 200062, P.R. China.
Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai, 200438, P.R. China.
Nat Commun. 2023 Nov 22;14(1):7611. doi: 10.1038/s41467-023-43202-5.
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 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.
最近，烯烃的不对称双官能团化受到了广泛关注。然而，对映选择性烷氧基烯基化的发展面临着相当大的挑战，并且在很大程度上滞后了。在此，我们报道了一种新的钯催化对映选择性烷氧基烯基化反应，该反应使用了一系列伯、仲和叔γ-羟基烯烃与卤代烯烃。通过使用新鉴定的在PCy基序相邻位置带有合适侧链的徐氏膦配体（Xu8和Xu9），以高达95%的对映体过量（ee）得到了一系列烯丙基取代的四氢呋喃，产率良好。除了（E）-卤代烯烃外，还考察了（Z）-卤代烯烃，并以单一非对映异构体形式得到了相应的（Z）-产物，这支持了立体专一性的氧化加成和还原消除步骤。此外，采用氘代标记和振动圆二色性（VCD）实验来确定顺式氧钯化机理。密度泛函理论（DFT）计算帮助我们更深入地了解侧链对手性配体的影响。最后，通过克级规模的合成以及产物的多种转化进一步证明了该方法的实用性。
