The first enantioselective vinylogous Mannich reaction is developed using 2-methoxyfuran under chiral spirophosphoric acid catalysis. The strategy involves 4-isoxazoline derivatives as cyclic ketimine surrogates and provides γ-butenolide scaffolds (up to 97% ee and >20:1 dr). The mechanistic investigations suggest that an in situ generated water molecule plays a crucial role in delivering γ-butenolide, while the use of molecular sieves delivers aza-Friedel–Crafts products. The synthetic utility of γ-butenolide is shown toward obtaining piperidone skeleton via a lactone-lactam rearrangement.

中文翻译：

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手性螺磷酸催化 2-甲氧基呋喃的发散乙烯基曼尼希和氮杂弗里德尔-克来福特反应


第一个对映选择性插烯曼尼希反应是在手性螺磷酸催化下使用 2-甲氧基呋喃开发的。该策略涉及 4-异恶唑啉衍生物作为环状酮亚胺替代物，并提供 γ-丁烯内酯支架（高达 97% ee 和 >20:1 dr）。机理研究表明，原位生成的水分子在输送γ-丁烯内酯方面发挥着至关重要的作用，而使用分子筛则可输送氮杂-弗里德尔-克拉夫茨产品。 γ-丁烯内酯的合成用途被证明可通过内酯-内酰胺重排获得哌啶酮骨架。