Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, United States.
J Org Chem. 2011 Jun 3;76(11):4337-57. doi: 10.1021/jo2005457. Epub 2011 May 6.
Although the synthetic utility of asymmetric phase-transfer catalysis continues to expand, the number of proven catalyst types and design criteria remains limited. At the origin of this scarcity is a lack in understanding of how catalyst structural features affect the rate and enantioselectivity of phase transfer catalyzed reactions. Described in this paper is the development of quantitative structure-activity relationships (QSAR) and -selectivity relationships (QSSR) for the alkylation of a protected glycine imine with libraries of quaternary ammonium ion catalysts. Catalyst descriptors including ammonium ion accessibility, interfacial adsorption affinity, and partition coefficient were found to correlate meaningfully with catalyst activity. The physical nature of the descriptors was rationalized through differing contributions of the interfacial and extraction mechanisms to the reaction under study. The variation in the observed enantioselectivity was rationalized employing a comparative molecular field analysis (CoMFA) using both the steric and electrostatic fields of the catalysts. A qualitative analysis of the developed model reveals preferred regions for catalyst binding to afford both configurations of the alkylated product.
尽管不对称相转移催化的合成实用性不断扩大，但已证实的催化剂类型和设计标准的数量仍然有限。这种稀缺性的根源在于缺乏对催化剂结构特征如何影响相转移催化反应的速率和对映选择性的理解。本文介绍了用于保护的甘氨酸亚胺与季铵离子催化剂库的烷基化反应的定量构效关系（QSAR）和对映选择性关系（QSSR）的发展。发现包括铵离子可及性、界面吸附亲和力和分配系数在内的催化剂描述符与催化剂活性有意义地相关。通过界面和提取机制对所研究的反应的不同贡献，对描述符的物理性质进行了合理化。通过使用催化剂的空间和静电场进行比较分子场分析（CoMFA），对观察到的对映选择性的变化进行了合理化。所开发模型的定性分析揭示了催化剂结合的优选区域，以提供烷基化产物的两种构型。
