Stereogenic Organocopper Reagents

这项工作的目的是了解和发展立体生成的有机铜试剂的反应化学。我们将探索这些“手性碳负离子”的反应性范围，特别是将制备各种α-烷氧基铜酸盐和α-氨基烷基铜酸盐，并考察它们的乙烯化、酰化、共轭加成和取代反应的立体选择性。不对称去质子化和跨金属化将被用作制备这些试剂的路线，对于任何这些路线可能失败的衬底，将通过动态热力学拆分来制备立体生成的铜酸盐。将努力确定有机铜试剂的结构和反应动力学，以提供最高的对映和非对映选择性。通过这一奖项，有机和高分子化学项目支持克莱姆森大学化学系R.Karl Dieter博士的研究。迪特尔博士将探索立体化学富集型有机铜试剂的反应化学。在手性分子中形成碳-碳键的能力(有两个不可重叠的镜像)并且只形成两种可能形式中的一种(单一对映体)是当今制药业面临的最重要的问题之一。开发出来后，Dieter博士的工作可以应用于合成具有抗菌剂、中枢神经系统药物和抗逆转录病毒化合物活性的含氮和含氧杂环化合物。在这项工作过程中接受培训的学生将获得制药业所需的技能，制药业现在生产许多单一的对映体化合物。

The objective of this work is to understand and develop the reaction chemistry of stereogenic organocopper reagents. The scope of reactivity of these "chiral carbanions" will be explored; specifically a variety of alpha alkoxyalkyl cuprates and alpha amino alkyl cuprates will be prepared and the stereoselectivity of their vinylation, acylation, conjugate addition, and substitution reactions will be investigated. Asymmetric deprotonation and transmetallation will be used as routes to prepare these reagents and for any substrate where these routes might fail then stereogenic cuprates will be prepared by dynamic thermodynamic resolution. Efforts to determine the structures of the organocopper reagents and kinetics of reactions that provide the highest enantio- and diastereoselectivites will be undertaken. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. R. Karl Dieter of the Department of Chemistry at Clemson University. Dr. Dieter will explore the reaction chemistry of stereochemically enriched organocopper reagents. The ability to form carbon-carbon bonds in molecules which are chiral (have two nonsuperimposable mirror images) and make only one of the two possible forms (a single enantiomer) is one of the most important problems facing the pharmaceutical industry today. When developed, Dr. Dieter's work could be applied to the synthesis of nitrogen and oxygen containing heterocycles with activities as antibacterial agents, CNS agents, and antiretroviral compounds. Students trained during the course of this work will gain skills needed by the pharmaceutical industry which now produces a number of single enantiomer compounds.