Alkali Metal Chemistry-Structures, Mechanisms, and Applications

碱金属化学-结构、机理和应用

• 批准号: 10393518
• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10393518
• 关键词: Address; Alkali Metals; Amides; Chemistry; Goals; Industrialization; Kinetics; Laboratories; Lithium; Metals; Methods; Molecular; Organometallic Chemistry; Pharmacologic Substance; Process; Reaction; Reagent; Resolution; Role; Sodium; Structure; base; computer studies; enolate; insight; interest; programs; stereochemistry; virtual

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.

总结与摘要 有机碱金属试剂用于学术和工业 实验室进行重要药用化合物的合成。 聚集体和溶剂化的核心重要性导致这些试剂如下 在结构和机械上与有机金属的任何分支学科一样令人困惑 通过结构和机械研究的结合，我们解决了关键问题。 有关反应性和选择性的问题该程序已完全集成。 从综合目标、观察或问题出发，通过结构、 机械和计算研究，并以综合有用的见解结束 将溶剂化视为分子现象而不是整体现象是核心。 到我们所有的学习。 我们将强调非共价助剂的作用并重点关注两个子集 事实证明，经过仔细审查实际上无法理解的碱金属化学： 烯醇锂和氨基钠这两个领域都需要共同努力，包括（1）。 对严重缺乏基本结构和机械原理的阐明，以及（2） 推动机制驱动，制定新的控制策略 在烯醇化方案中，我们强调混合的作用。 以手性锂醇盐作为载体来控制相对和绝对 在有机钠化学方面，我们将继续研究其原理。 结构和机制的发展完全缺乏反应性和原理 钠基试剂与锂基试剂的众多差异。 迄今为止发现的，是催化有机钠与三胺反应的能力 我们将重点关注具有催化活性的手性三胺来诱导。 通过氨基钠和催化不对称的动力学拆分进行立体控制 我们的圣杯是找到所得的钠化中间体的功能化。 通用添加剂——用于烯醇锂的氨基醇盐和用于 有机钠反应。