The asymmetric total synthesis of fasicularin by a chiral N-alkoxyamide strategy is reported. Incorporation of the chiral alkoxy group onto an amide nitrogen changes the original reactivity of the amide, enabling two key transformations: aza-spirocyclization and the reductive Strecker reaction. DFT calculations indicate that pyramidalization of the N-alkoxyamide nitrogen is crucial to produce a cyclic hemiaminal in equilibrium, which undergoes aza-spirocyclization. The chiral alkoxy group is also used as a stereocontrol element to establish two consecutive stereocenters. The iridium-catalyzed reductive Strecker reaction of the N-alkoxylactam provides the aminonitrile with high diastereoselectivity.

中文翻译：

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手性 N-烷氧基酰胺策略的开发及在包茎蛋白不对称全合成中的应用

报道了通过手性 N-烷氧基酰胺策略不对称全合成 fasicularin。将手性烷氧基结合到酰胺氮上会改变酰胺的​​原始反应性，从而实现两个关键转化：氮杂-螺环化和还原性 Strecker 反应。DFT 计算表明 N-烷氧基酰胺氮的锥体化对于产生平衡的环状半胺醛至关重要，该半胺醛经历氮杂-螺环化。手性烷氧基也用作立体控制元素以建立两个连续的立体中心。N-烷氧基内酰胺的铱催化还原 Strecker 反应为氨基腈提供了高非对映选择性。