An epimerization–lactamization cascade of functionalized (2S,4R)-4-aminoproline methyl esters is developed and applied in synthesizing (1R,4R)-2,5-diazabicyclo[2.2.1]heptane (DBH) derivatives. (2S,4R)-4-Aminoproline methyl esters are likely to undergo 2-epimerization under basic conditions, followed by an intramolecular aminolysis of the (2R)-epimer to form the bridged lactam intermediates. Key factors identified for this cascade reaction include the electron-withdrawal N-protective group in the substrates and a strong base as the promoter.

中文翻译：

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差向异构-内酰胺化级联反应 合成（1 R，4 R）-2,5-二氮杂双环[2.2.1]庚烷衍生物

开发了功能化的（2 S，4 R）-4-氨基脯氨酸甲酯的差向异构-内酰胺化级联，并将其应用于合成（1 R，4 R）-2,5-二氮杂双环[2.2.1]庚烷（DBH）衍生物。（2 S，4 R）-4-氨基脯氨酸甲酯很可能在碱性条件下发生2-异构化，然后（2 R）-异构体的分子内氨解反应形成桥连的内酰胺中间体。确定用于该级联反应的关键因素包括底物中的吸电子N保护基和作为促进剂的强碱。