基于alpha-手性炔丙胺的多样性合成研究

Chiral propargylic amines are highly functionalized building blocks, however, synthetic methods based on this class of compounds have not been extensively developed. This project aims at diversity-oriented synthesis. Capitalizing on our recent synthesis of alpha-chiral propargylic amines, we plan to develop the synthetic protocols for key building blocks and structural motifs such as 1) convertible E-alpha-allylic amines; 2) tri-substituted alpha-chiral allylic amines with defined olefin geometry; 3) chiral 1,3-amino alcohols; 4) enantiopure alpha-/beta-/gamma-amino acids; 5) di-and tri-substituted chiral allenes; and 6) poly-substituted chiral pyrrol-2(5H)-ones and pyrrolidines. The significance of this project lies in that the above-mentioned targets are of great synthetic and biological value, while current methods for their preparation need to be improved. The main objects of this research program are controlled transformation (functionalization) of alpha-hetero-substituted alkenes; selective activation and cleavage of stable carbon-hetero bond; and stereoselective hydroboration of acyclic alkenes. In summary, this project will promote the chemistry of propargylic amine and diversity-oriented synthesis.

手性炔丙胺具有高度官能化，基于这类化合物的合成方法学还未受到应有的重视。本项目着眼于结构多样性合成研究，在本组报道的手性炔丙胺合成基础上，致力于发展：1) 可转化的E-alpha-手性烯丙胺、2) 构型确定的三取代alpha-手性烯丙胺、3) 手性1,3-氨基醇、4) 高对映纯度的 alpha-/beta-/gamma-氨基酸、5) 二取代和三取代手型联烯、和6) 多取代手性吡咯-2(5H)-酮及多取代四氢吡咯等几类重要化合物的合成方法学。上述目标结构作用重要，而现有合成方法局限性较大，因此本项研究具有重要意义。主要尝试解决alpha-杂原子取代炔烃的可控化学转化 (功能化)、稳定碳杂键的选择性活化和断裂、非环烯烃的立体选择性硼氢化反应等方面的科学问题。综上所述，本项目的研究有助于促进炔丙胺化学和多样性合成的发展。

基于炔丙胺的合成方法学尚未得到应有的重视。本项目着眼于多样性合成，以手性炔丙胺为原料，发展了：1）一种E-专一的还原方法，制备手性烯丙胺，甚至可用于含有手性季碳的alpha,alpha-二取代手性烯丙胺；2）一种构型确定的三取代alpha-手性烯丙胺的合成方法；3）高对映纯度的alpha-/beta-/gamma-氨基酸的合成方法；4) 一种官能化的三氮唑化合物的合成方法，提出并验证了铜催化条件下的酰胺羰基的邻基参与脱硅机理。另外在以炔丙胺为原料合成多取代联烯方面作了一些尝试。