Acid-Catalyzed Z-E Isomerization of γ-Alkylidenebutenolides: An Experimental and DFT Study

The Z-E isomerization of γ-alkylidenebutenolide analogues to natural nostoclides and other natural butenolides was investigated using 1H nuclear magnetic resonance (NMR) and high performance liquid chromatography (HPLC) data as well as density functional theory (DFT) calculations at the wB97x-D/6-31G(d,p) level, including solvent effects with the polarizable continuum solvation approach. The experimental data supported the Z to E isomerization of γ-alkylidenebutenolides under acid catalysis. Newly prepared samples have predominantly Z configuration, which partially isomerizes to the E isomer under acidic conditions. Density functional theory studies corroborate the experimental findings. While neutral γ-alkylidenebutenolides are more stable in the Z form, protonation of the γ-lactone carbonyl group results in preferential stabilization of the E isomer.

本研究采用1H核磁共振（1H nuclear magnetic resonance, NMR）、高效液相色谱（High Performance Liquid Chromatography, HPLC）数据，结合wB97x-D/6-31G(d,p)级别下的密度泛函理论（Density Functional Theory, DFT）计算（采用极化连续溶剂化模型考量溶剂效应），探究了γ-亚烷基丁烯内酯（γ-alkylidenebutenolide）类似物向天然诺斯托克内酯（nostoclides）及其他天然丁烯内酯的Z-E异构化反应。实验数据证实，γ-亚烷基丁烯内酯在酸催化条件下可发生Z型向E型的异构化。新制备的样品主要以Z构型存在，在酸性条件下会部分异构为E型异构体。密度泛函理论研究结果佐证了实验发现。尽管中性状态的γ-亚烷基丁烯内酯更稳定的构型为Z型，但γ-内酯羰基的质子化会使E型异构体获得优先稳定性。