不对称铜催化的基于[1,n]-BoraBrook重排的串联反应研究

作为构建碳-碳键的重要方法之一，Brook重排-串联反应在有机合成中的应用仍面临着一些关键因素的制约：（1）立体选择性控制的催化[1,n]-Brook（n > 2）重排反应还未实现；（2） 参与串联反应的试剂局限于亲电试剂；（3）存在“逆”Brook重排反应。针对上述科学问题，本项目拟开展不对称铜催化的[1,n]-BoraBrook重排-串联反应研究。基于共轭体系中π电子的流动特点，本项目设计并合成含C=X不饱和键的化合物，并在铜盐/手性配体的催化下实现其与不饱和烃（包括富电子、缺电子不饱和烃，芳香杂环等）的不对称[1,n]-BoraBrook（n = 2, 3, 4）重排-串联反应，实现手性醇、胺类化合物的合成，并探索其在功能有机分子合成中的应用。同时，本项目将深入探讨反应机理，建立BoraBrook重排-串联反应设计的新理论。本项目的研究成果将为有机化合物中碳-碳键的构筑提供新思路。

The Brook rearrangement followed by cascade reaction is one of the powerful methods that construct carbon-carbon bond, but it still has several drawbacks: (1) Stereoselective catalytic [1,n]-Brook (n > 2) rearrangement has not been discovered; (2) Cascade reaction partners are confined to electrophiles; (3) Retro-Brook rearrangement acts as a side reaction. In consideration of these challenges, this project focuses on asymmetric Cu-catalyzed cascade reaction involving [1,n]-BoraBrook rearrangement. Based on the “domino” movement of π electrons in conjugate systems when attacked by nucleophiles, we design and synthesize different types of compounds containing C=X double bond, and develop asymmetric [1,n]-BoraBrook rearrangement of these compounds followed by cascade reaction with unsaturated hydrocarbons (including electron-rich and electron-deficient ones) or heteroaromatics in the presence of copper salts and chiral ligands, and finally achieve chiral alcohols, amines, and heterocycles. Meanwhile, we probe deeply into the mechanism and establish a theory for the design of novel BoraBrook rearrangement-cascade reactions. The achievements of this project may provide chemists with new options to construct carbon-carbon bonds in various organic compounds.