基于分子内不对称N-H插入/aza-Claisen重排策略构建手性中环分子

手性中环是构成许多生物活性天然产物和药用合成化合物的重要结构单元。然而，手性中环化合物很难通过传统的环合方法直接构建。通过手性小环化合物的重排扩环是合成手性中环化合物行之有效的方法，但其手性前体绝大部分通过手性天然产物转化，缺乏通用的不对称合成方法。手性环状烯丙基胺化合物可以作为aza-Claisen重排反应的前体，并且有可能通过分子内金属卡宾不对称插入N-H键反应合成得到，但目前并没有这方面的相关报道。本项目拟将挑战首例一价铑催化的分子内金属卡宾不对称插入N-H键反应，通过底物的合理设计及反应条件优化，发展一种高效通用的方法不对称合成不同类型的手性环状烯丙基胺化合物，并将它们作为重排扩环前体，基于aza-Claisen重排扩环策略合成一系列结构多样的手性氮杂中环分子,为其它更多手性中环分子的合成提供新思路。

Chiral medium-ring is an important structural unit of many bioactive natural products and medicinal compounds. However, it is difficult to synthesize the chiral medium-ring compounds through traditional cyclization methods. The ring expansion of chiral small ring compounds is an effective method to synthesize chiral medium-ring compounds, but lack of general asymmetric synthetic methods of the chiral precursors. As the precursors of the aza-Claisen rearrangement reaction, the chiral cyclic allylamine compounds may be synthesized by the asymmetric intramolecular carbene insertion into the N-H bonds, but there is no relevant report so far. This project will achieve the first example of Rh(I) catalyzed intramolecular asymmetric carbene insertion into N-H bonds. Through the reasonable design of substrates and reaction conditions optimization, we will develop an effective and general method to synthesize the chiral aza-Claisen rearrangement precursors, and then synthesize a series of chiral medium-ring molecules with structural diversity based on aza-Claisen rearrangement ring expanding strategy.