Thiourea-Catalyzed Nucleophilic Desymmetrization of Meso-Cyclopropanes

硫脲催化内消旋环丙烷的亲核去对称化

• 批准号: 7328962
• 负责人: Kristine Nolin
• 金额: $ 4.48万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7328962
• 关键词: Active Sites; Benign; Breathing; Caring; Catalysis; Chemicals; Complex; Cyclopropanes; Development; Drug Industry; Enzymes; Facility Construction Funding Category; Goals; Metals; Methodology; Nature; Reaction; Research; Thiourea; Transition Elements; catalyst; cyclopropane; functional group; interest; metal complex; scaffold; tool

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.

描述（由申请人提供）：不对称催化为合成对映体纯的生物活性分子提供了必要的合成工具。不对称催化领域一直被过渡金属配合物的应用所主导。过渡金属催化反应的使用引起了化学和制药工业的严重关注。在与使用过渡金属催化剂相关的纯化和处置实践中必须非常小心，因为许多这些络合物是有毒的。为了开发这些实践的替代品，化学家们转向自然界寻求灵感，开发更有效，选择性和环境友好的催化剂，用于有用的有机转化。随着对酶功能背后机制的了解的增加，在过去十年中，人们对使用有机分子作为不对称有机转化催化剂的兴趣爆发。在许多酶的活性部位不存在金属，这证明了非金属官能团作为催化中心的能力。化学家们正试图用小的有机化合物来模拟这些非金属活性部位。本文综述了硫脲催化的内消旋环丙烷亲核开环去对称化反应在羰基化合物的立体选择性1，5-官能化反应中的应用。目前的合成方法允许内消旋环丙烷的简易构建，并且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的同时活化。本研究的目的是开发硫脲类化合物作为催化剂，用于这一转变。