钯催化烯丙基底物的不对称环丙烷化反应的研究

Investigation the following aspects for the Pd-catalyzed asymmetric cyclopropanation of allylic substrates: 1.To investigate the mechanism by using the α-carbanion of amide as nucleophile,to explore the causation of cyclopropanation by studying the character of active intermediate in the reaction. 2.Via modifying the ligands' stereochemistry and electro-property to increase the reactivity of the central carbon in the [η3-allyl-PdL] complex. Modification based on the structure of SIOC-Phox (Sphos, R)-L1.Using the α-carbanions as nucleophiles from substrates 2、3 respectively, to investigate the reactivity for allylic cyclopropanation under the chiral palladium complex catalyzed. Based on the primary results to adjust the ligands' structure purposely. 3.To investigate the effect of the nucleophiles and allylic substrates in the reaction,and to develop the scope of the substrates. To endeavor to discover some principles during the investigation for designing novel ligands to the new nucleophiles. To investigate the application of the reaction in synthesis chemistry by applying the products in some natural products' synthesis.

钯催化烯丙基底物的不对称环丙烷化反应的研究从以下几个方面来探索： 1．以底物酰胺1的α-碳负离子为亲核试剂来探索该反应的机理,探索活性催化剂本身的特性与其所给出的实验结果之间的因果关系; 2.通过对配体的电子效应和空间立体效应的改变来提高[η3-allyl-Pd]中间体的中间碳接受亲核试剂进攻的反应活性。在SIOC-Phox(Sphos,R)-L1配体结构的基础上进行改造。在所取得的初步实验结果基础上，有针对性的对配体进行进一步改造； 3.考察亲核试剂和烯丙基底物对反应的影响，并扩展底物的范围。 努力从上述的实验结果中总结出一些规律以便于修饰改造或者设计合成配体进而发展出适于新的亲核试剂类型的反应催化体系。 另外，将所得产物应用到合适的活性小分子的合成中。

我们对酰胺与烯丙基试剂的环丙烷化反应做了深入研究：通过单晶X-衍射分析，核磁实验等一系列实验确定了反应活性中间体，从SIOCPhox-Pd-allyl complex发现烯丙基取代和环丙烷化反应活性中间体的结构差异。并结合计算化学，进行了不同烯醇离子和烯丙基金属络合物的轨道能量计算，发现亲核试剂HOMO轨道的能量差异与其环丙烷化结果平行，说明亲核试剂、烯丙基金属络合物前沿轨道的差异对反应的影响，提示该反应可能是轨道控制。据此，设计合成了NHC-Py类配体，实现了羧酸酯和叔丁基乙基酮的环丙烷化。在以叔丁基乙基酮为亲核试剂的反应中与使用没有取代基的配体结果相比有了明显提高。这些结果表明通过配位原子的配位化学、调节前沿轨道能量实现不同亲核试环丙烷化的可能性。