基于一价铜硼酸酯络合物对1,3-烯炔加成的不对称催化的串联环化反应

本项目以手性一价铜络合物为催化剂，研究1,3-烯炔、联硼酸酯和四类亲电试剂间的不对称串联环化反应。在碱的作用下，手性一价铜络合物和联硼酸酯发生金属转移反应生成手性Cu(I)-BPin络合物，它与1,3-烯炔发生加成反应生成高活性的联烯基一价铜物种。新生成的联烯基一价铜物种与1,3-环二酮中的一个酮羰基和基于内消旋的1,3-环状二醇的双离去基团中的一个分别发生分子内的加成反应和取代反应而生成含有多个连续手性中心的双环体系，此串联环化反应将被作为主要反应方法学用于天然产物分子Solidago Alcohol的不对称全合成；另外，联烯基一价铜物种与酰亚胺中的一个羰基和弱活化的吡啶盐分别发生分子内的加成反应而生成含有多个连续手性中心的高度官能化的含氮双环体系，此串联环化反应将被作为主要反应方法学用于天然产物分子Indicine N-oxide的不对称全合成。

This project is focusing on the asymmetric tandem cyclization of 1,3-enynes, B(Pin)2 and various electrophiles (four types). In the presence of a base, copper(I) complex reacts with B(Pin)2 to form Cu(I)-BPin through transmetalation, which reacts with 1,3-enynes to generated a reactive allenyl copper(I) species. Firstly, the allenyl copper(I) species reacts with one carbonyl group of cyclic 1,3-diketone through intramolecular nucleophilic addition to afford a chiral bicyclic skeleton containing four contiguous chiral centers (one of them is all-carbon quaternary stereogenic carbon center). This reaction will be employed as a key methodology to carry out the asymmetric total synthesis of solidago alcohol. Secondly, the allenyl copper(I) species reacts with one of the two leaving groups based on racemic cyclic 1,3-diol through intramolecular nucleophilic substitution to give a chiral bicyclic skeleton containing five contiguous chiral centers. Thirdly, the allenyl copper(I) species reacts with one carbonyl group in the cyclic imide through intramolecular nucleophilic addition to produce a chiral heterobicyclic skeleton containing three contiguous chiral centers. This reaction will be applied to the asymmetric total synthesis of Indicine N-oxide, which exhibited anti-tumor activity and toxicity. Fourthly, the allenyl copper(I) species reacts with pyridinium through intramolecular nucleophilic addition to provide a highly functionalized chiral heterobicyclic skeleton containing three contiguous chiral centers.