Herein we report our observations from the study of the classical Robinson annulation reaction under solvent‐free mechanochemical activation by means of high‐speed ball milling. In particular, the enantioselective synthesis of the Wieland‐Miescher ketone was used as model reaction. (S)‐Proline was employed as chiral organocatalyst, either alone or in the presence of additives in order to determine their influence on the reaction’s speed and stereoselectivity. Most interesting, among the additives that were examined, four solvate ionic liquids (SIL) afforded the desired product with significantly improved enantioselectivity relative to the mechanochemically‐activated reaction catalyzed by (S)‐proline alone. Furthermore, the required reaction time was reduced from 3 days to 90 min. The potential of other proline‐type organocatalysts was explored in this ball‐milling process. Initial attempts to increase the scope of the reaction to afford related annulation products were unsuccessful. HPLC‐MS experiments were carried out in order to detect some of the species that intervene in the mechanism of the (S)‐proline‐catalyzed Robinson cyclization reaction involving 2‐methyl‐1,3‐cyclohexanedione and methyl vinyl ketone.

中文翻译：

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溶剂化离子液体在对映选择性 (S)-脯氨酸催化的机械化学罗宾逊成环中的作用。


在此，我们报告了通过高速球磨在无溶剂机械化学活化下经典罗宾逊成环反应研究的观察结果。特别是，维兰德-米歇尔酮的对映选择性合成被用作模型反应。 (S)-脯氨酸单独或在添加剂存在下用作手性有机催化剂，以确定它们对反应速度和立体选择性的影响。最有趣的是，在所检查的添加剂中，四种溶剂化离子液体 (SIL) 提供了所需的产物，相对于仅由 (S)-脯氨酸催化的机械化学激活反应，其对映选择性显着提高。此外，所需的反应时间从 3 天减少到 90 分钟。在这个球磨过程中探索了其他脯氨酸型有机催化剂的潜力。最初尝试扩大反应范围以提供相关的环状产物，但没有成功。进行 HPLC-MS 实验是为了检测一些干扰涉及 2-甲基-1,3-环己二酮和甲基乙烯基酮的 (S)-脯氨酸催化 Robinson 环化反应机制的物质。