Thiourea-Catalyzed Nucleophilic Desymmetrization of Meso-Cyclopropanes

描述(申请人提供)：不对称催化为合成对映体纯净的生物活性分子提供了必要的合成工具。在不对称催化领域，过渡金属络合物的使用一直占据主导地位。过渡金属催化反应的使用引起了化工和制药行业的严重关注。与使用过渡金属催化剂相关的提纯和处理方法必须非常小心，因为许多过渡金属络合物是有毒的。为了开发这些实践的替代品，化学家们从大自然中获得灵感，开发出更高效、更具选择性和环境友好的催化剂，以实现有用的有机转化。随着人们对酶作用机理认识的加深，在过去的十年里，人们对有机分子作为不对称有机转化催化剂的兴趣与日俱增。许多酶的活性部位没有金属，这表明非金属官能团具有催化中心的能力。化学家们正试图用小型有机化合物来模拟这些非金属活性中心。这一建议概述了通过硫脲催化中位环丙烷亲核开环去对称化1，5-官能化的研究进展。目前的合成方法可以方便地构建中位环丙烷，它们的去对称化将产生复杂的手性支架。硫脲催化剂的双功能性质应导致环丙烷和亲核试剂同时活化。本研究的目的是开发硫脲类化合物作为催化这一转化的催化剂。

DESCRIPTION (provided by applicant): Asymmetric catalysis provides necessary synthetic tools for the synthesis of enantiomerically pure, biologically active molecules. The field of asymmetric catalysis has been dominated by the use of transition metal complexes. The use of transition metal catalyzed reactions poses grave concerns for the chemical and pharmaceutical industry. Great care must be taken in purification and disposal practices associated with the use of transition metal catalysts, as many of these complexes are toxic. To develop alternatives to these practices, chemists have turned to nature for inspiration in the development of more efficient, selective, and environmentally benign catalysts for useful organic transformations. With an increase in the understanding of the mechanisms behind enzyme function, interest has erupted over the last decade in the use of organic molecules as catalysts for asymmetric organic transformations. The absence of metals at the active site of many enzymes demonstrates the ability of non-metallic functional groups to serve as catalytic centers. Chemists are attempting to mimic these non-metallic active sites with small organic compounds. This proposal outlines the development of stereoselective 1,5-functionalization of carbonyls through thiourea catalyzed desymmetrizations of meso-cyclopropanes by nucleophilic ring opening. Current synthetic methodologies allow for the facile construction of meso-cyclopropanes and their desymmetrization would give rise to complex chiral scaffold. The bifunctional nature of the thiourea catalysts should result in simultaneous activation of the cyclopropane as well as the nucleophile. The goal of this research is to develop thiourea compounds as catalysts for this transformation.