Structure Based Development of Organic Reactions

基于结构的有机反应发展

• 批准号: 0718275
• 负责人: Paul Williard
• 金额: $ 38.8万
• 依托单位: Brown University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0718275&HistoricalAwards=false
• 关键词: Structure; Based; Development; Organic; Reactions

AbstractStructure Based Development of Organic ReactionsAlkali metal and a very few additional cationic metal stabilized reagents such as boron, zinc, titanium and platinum are the most widely utilized organometallic reagents in organic synthesis today. However, many unanswered questions concerning their solution and solid-state structures remain. Specific aim 1 of this proposal is designed to enhance our understanding of the aggregation state, the coordination number, the geometry of attached ligands, and the intimate structural features of such reagents. Results of this project will provide models for use in developing new reagents and in optimizing the stereoselectivity of extant reagents. The second specific aim of this project is designed to synthesize and characterize new reagents and to develop asymmetric synthetic methodology utilizing new chiral polymeric reagents that will be prepared in my lab. The design of new polymers will be based upon structure motifs of reactive intermediates from my lab. New equipment will be designed and protocols developed from growing, sorting and manipulating extremely reactive, extremely moisture sensitive and extremely temperature sensitive organometallic compounds in preparation for their characterization by x-ray diffraction analysis. Hence, a high throughput crystal screening apparatus and protocol will be developed in analogy to the protocols that have proven highly successful for high throughput preparation of macromolecular protein crystals.Broader Impact: Stereoselectivity is the basis for synthesizing pure, chiral chemical compounds. Structural details are especially important for the optimization of stereoselectivity in the design of new reagents and catalysts. Speculative and unproven structural postulates typically have been utilized for this purpose. However knowledge of the intimate structure of these reagents remains woefully incomplete and is not commensurate with the widespread, successful use of these reagents in practice. Nonetheless it is encouraging that there is a very good correlation between the structures of these reagents and their reactivity. Hence, I propose a research program designed to obtain structural information that will be utilized to prepare new chiral polymers and to improve the efficiency with which new chemical compounds are prepared. Specific to this proposal is a focus on boron enolate reagents and chiral lithium amide bases. New reagents that we develop will be optimized for the synthesis of chiral molecules utilized as catalysts and as building blocks for larger molecules. Success of this project directly and positively affects the efficiency with which new materials, nanostructures, polymers, and bulk organic chemicals are discovered and prepared. All students in my research group develop expertise in organic synthesis, spectroscopic analyses, chromatography and x-ray diffraction analysis with a major emphasis on acquiring the skills necessary to continue independent research in a chemical, materials or biochemical research laboratory. I actively recruit students to participate in this program in collaboration with ongoing initiatives at Brown University including the Leadership Alliance (minority undergraduates), NSF COACH grant (graduate women in science), UTRA (undergraduate teaching and research), WISE (undergraduate women in science & engineering) and Beckman Foundation (undergraduate research training) programs. I am especially pleased with success we have had in the inclusion of minority, female undergraduates identified through the Leadership Alliance and WISE programs.

摘要基于结构的有机反应发展碱金属和极少数附加的阳离子金属稳定试剂（例如硼、锌、钛和铂）是当今有机合成中使用最广泛的有机金属试剂。 然而，有关其解决方案和固态结构的许多未解答的问题仍然存在。 该提案的具体目标 1 旨在增强我们对聚集态、配位数、连接配体的几何形状以及此类试剂的密切结构特征的理解。 该项目的结果将为开发新试剂和优化现有试剂的立体选择性提供模型。该项目的第二个具体目标是合成和表征新试剂，并利用将在我的实验室制备的新型手性聚合物试剂开发不对称合成方法。 新聚合物的设计将基于我实验室的反应性中间体的结构图案。 将设计新设备并开发方案，对反应性极强、湿度极敏感和温度极敏感的有机金属化合物进行生长、分类和操作，为通过 X 射线衍射分析对其进行表征做好准备。 因此，将开发高通量晶体筛选装置和方案，类似于已被证明在高通量制备大分子蛋白质晶体方面非常成功的方案。更广泛的影响：立体选择性是合成纯手性化合物的基础。 结构细节对于新试剂和催化剂设计中立体选择性的优化尤其重要。 推测性的和未经证实的结构假设通常被用于此目的。 然而，遗憾的是，对这些试剂的内部结构的了解仍然不完整，并且与这些试剂在实践中广泛、成功的使用不相称。 尽管如此，令人鼓舞的是这些试剂的结构与其反应性之间存在非常好的相关性。 因此，我提出了一项研究计划，旨在获取结构信息，用于制备新的手性聚合物并提高新化合物的制备效率。 该提案的具体重点是硼烯醇试剂和手性氨基锂碱。 我们开发的新试剂将针对用作催化剂和较大分子构建模块的手性分子的合成进行优化。 该项目的成功直接、积极地影响了新材料、纳米结构、聚合物和大宗有机化学品的发现和制备的效率。 我研究小组的所有学生都发展有机合成、光谱分析、色谱和 X 射线衍射分析方面的专业知识，重点是获得在化学、材料或生化研究实验室继续独立研究所需的技能。 我与布朗大学正在进行的项目合作，积极招募学生参与该项目，包括领导力联盟（少数族裔本科生）、NSF COACH 资助（科学领域的女性研究生）、UTRA（本科生教学和研究）、WISE（科学与工程领域的本科女性）和贝克曼基金会（本科生研究培训）项目。 我对我们在包容通过领导力联盟和 WISE 项目确定的少数族裔女本科生方面取得的成功感到特别高兴。