Alkali Metal Chemistry-Structures, Mechanisms, and Applications

碱金属化学-结构、机理和应用

基本信息

批准号：
10605229
负责人：
DAVID B. COLLUM
金额：
$ 55.76万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2024-04-30
项目状态：
已结题

项目摘要

Summary and Abstract Organoalkali metal-based reagents are used in both academic and industrial laboratories to carry out syntheses of medicinally important compounds. The underlying aggregates and central importance of solvation cause these reagents to be as structurally and mechanistically confounding as any subdiscipline in organometallic chemistry. Through a combination of structural and mechanistic studies we address key issues pertaining to reactivity and selectivity. The program is fully integrated starting from a synthetic goal, observation, or question, proceeding through structural, mechanistic, and computational studies, and finishing with synthetically useful insights and methods. Treating solvation as a molecular rather than bulk phenomenon is central to all of our studies. We will emphasize the role of non-covalent auxiliaries and focus on two subsets of alkali metal chemistry that have proven virtually impenetrable to careful scrutiny: lithium enolates and sodium amides. Both arenas require a combined effort involving (1) the elucidation of profoundly lacking basic structural and mechanistic principles, and (2) pushing a mechanism-driven approach to develop new strategies for controlling reactivity and selectivity. In the enolate program, we emphasize the role of mixed aggregates with chiral lithium alkoxides as vehicles to control relative and absolute stereochemistry. In the organosodium chemistry, we will continue studying the principles of structure and mechanism to develop completely absent principles of reactivity and selectivity. Among a multitude of differences of sodium- versus lithium-based reagents discovered so far, it is the capacity to catalyze organosodium reactions with triamines that stands out. We will focus on catalytically active chiral triamines to induce stereocontrol via kinetic resolutions by sodium amides and catalyzed asymmetric functionalizations of the resulting sodiated intermediates. The Holy Grail for us is finding universal additives—amino alkoxides for lithium enolates and chiral triamines for the organosodium reactions.

摘要和摘要基于有机金属金属的试剂在学术和工业中都使用实验室进行医学重要化合物的合成。基础解决方案的骨料和核心重要性导致这些试剂为在结构上和机械上混淆为有机的任何子学科化学。通过结构和机械研究的结合，我们解决了关键与反应性和选择性有关的问题。该程序已完全集成从综合目标，观察或问题中，通过结构性进行，机械和计算研究，并通过合成有用的见解完成和方法。将求解作为分子而不是散装现象是中心我们所有的研究。我们将强调非共价辅助机构的作用，并专注于两个子集碱金属化学物质几乎无法仔细审查。锂烯醇和钠酰胺。两个领域都需要涉及的综合努力（1）深刻缺乏基本的结构和机械原理的阐明，以及（2）推动一种机制驱动的方法来制定控制的新策略反应性和选择性。在钢化程序中，我们强调了混合的作用手性锂烷氧化物作为控制相对和绝对的车辆立体化学。在Organosososodium化学中，我们将继续研究原理结构和机制的完全不存在反应性原理和选择性。在钠基于锂的试剂的多种差异中到目前为止发现，它是催化有机钠反应的能力那是脱颖而出的。我们将专注于催化活跃的手性三字素来诱导通过钠酰胺的动力学分辨率立体控制，并催化不对称的分辨率产生的均匀中间体的功能化。对我们来说圣杯正在找到通用添加剂 - 用于锂烯醇的氨基烷氧化物和手性三胺有机钠反应。