Ligand-Enabled Palladium-Catalyzed Asymmetric Synthesis of Indole-Fused Chiral Eight-Membered N -Heterocycles via [4 + 4] Cycloaddition

作者：Zhengyi Yi, Weixin Xiao, Yong Liu, Lunyu Ou, Hongyun Li, Haijun Yang, Hua Fu · 发表于：Organic Letters · 年份：2025 · DOI：10.1021/acs.orglett.5c04101 · 被引用次数：9 · 研究领域：Axial and Atropisomeric Chirality Synthesis、Catalytic C–H Functionalization Methods、Asymmetric Synthesis and Catalysis

Indole-fused chiral eight-membered N -heterocycles are found in natural products and biologically active molecules. However, their synthesis still remains a great challenge due to the disadvantageous enthalpy and entropy factors as well as the transannular interactions. Therefore, it is highly desirable to develop an efficient and practical approach to indole-fused chiral eight-membered N -heterocycles with high stereoselectivity. In this paper, we have developed a palladium-catalyzed asymmetric [4 + 4] cycloaddition of α,β-unsaturated N - p -tosyl-iminoindoles with γ-methylidene-δ-valerolactones, and diverse and highly functionalized indole-fused chiral eight-membered N -heterocycles were prepared in high yields (60–88%), excellent diastereoselectivity (>20:1 dr), and high to excellent enantioselectivity (80–99% ee), in which our newly developed axially chiral phosphoramidite ligand obviously promoted the reactivity of the substrates and the stereoselectivity of the products. Further derivatization of the obtained products provided other indole-fused chiral eight-membered N -heterocycles.