新型手性三环季铵盐相转移催化剂的构建及其催化烯烃不对称氧化加成反应

Chiral phase-transfer catalysis(CPTC)is a successful achievement in green asymmetric synthesis. Up to now, most of chiral phase-transfer catalysts are derived from natural cinchona alkaloids and chiral axial binols for plenty of applications in asymmetric alkylations with excellent catalytic activities and enantioselectivities. However, few good example of CPTCs was found in asymmetric oxidation-addition of olefins. In this project, a series of chiral tricyclic quaternary ammonium salts were synthesized from commercially available starting materials meso-diethyl 2,5-dibromoadipate and (S)-α-methyl-benzylamine through amidation, Grignard reaction and one-pot ring closure and quaterization. The feature of these chiral quaternary ammonium salts is possessing a rigid azatricyclic skeleton with good modularity, and the systematic investigation of their catalytic activities and enantioselectivities in asymmetric amination, dihydroxylation and tandem oxa-Michael-Michael reaction of olefins will be performed. In our previous research, these CPTCs demonstrated excellent chiral induction in tandem oxa-Michael-Michael reaction to give the corresponding product with 95%de and 84%ee. The aim of this project is to obtain the universal chiral phase-transfer catalysts with excellent catlytic activities and enantioselectivities in above-mentioned three reactions and also provide a facile access to chiral compounds by environmentally friendly means.

手性相转移催化是绿色有机合成的典范，其核心是手性相转移催化剂。目前，手性相转移催化剂的设计合成依赖于金鸡纳生物碱和轴手性联萘骨架，仅在不对称烷基化反应中取得满意结果；而对于烯烃不对称氧化加成反应，其应用寥寥无几。为突破这一局限，本项目从内消旋2,5-二溴己二酸二乙酯和(S)-α-甲基苄胺出发，首次构建三类新颖的具有五元三骈刚性骨架、高度可调的手性三环季铵盐相转移催化剂，考察其在烯烃不对称胺基化、双羟化和Michael串联反应中的手性诱导性能。前期实验结果证实，该新型相转移催化剂在Michael串联反应中获得优异手性诱导效应（95%de和84%ee）。本项目预期首次实现相转移催化烯烃的不对称双羟化和Michael串联反应，归纳出催化剂、底物和溶剂对反应活性和立体选择性的影响，初步揭示其手性诱导规律，以期获得高效普适的新型手性季铵盐相转移催化剂和催化体系，为手性化合物的绿色高效合成提供捷径。

本项目主要进行了新型手性相转移催化剂的构建及其催化性能研究，项目整体按预定研究计划执行，取得了较好研究结果。.我们从价廉易得的试剂出发，分别以酒石酸、3-氨基吡咯烷、二茂铁、氨基酸和茚氨基膦五个优势骨架为基础，通过3~5步简单反应，快速构建了9个系列共50多个手性和非手性双功能相转移催化剂，采用NMR、HRMS等手段对其结构进行了表征和确定; 重点考察了它们在催化不对称胺基化反应、迈克尔环化反应和活化固定CO2反应等三类反应中的催化性能。经研究表明，构建的手性双功能相转移催化剂在水相催化烯烃的不对称胺基化反应中取得好的结果，化学产率高达96%，光学选择性高达93%ee；在催化不对称迈克尔环化反应中表现一般，仅获得39%ee的光学产率；在催化活化CO2反应方面表现突出，能在1 atm CO2压力下顺利催化CO2和环氧乙烷衍生物的环加成反应，以高达90%的化学产率获得各种取代的环碳酸酯。上述反应的催化剂负载量均在0.5~1 mol%之间，特别符合绿色有机合成化学的要求，为进一步实际应用打下良好基础。.本项目研究结果共发表基金资助SCI论文6篇，目前处于评审阶段的SCI论文稿件1篇；培养硕士研究生共4名。