The Chemistry of Lithium Amides

氨基锂的化学性质

• 批准号: 8244503
• 负责人: DAVID B. COLLUM
• 金额: $ 35.84万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8244503
• 关键词: Academia; Acetals; Acids; Age; Alkylation; Amides; Analytical Chemistry; Back; Case Study; Chemistry; Clinical Trials; Complex; Data; Development; Drug Industry; Epoxy Compounds; Esters; Event; Feedback; Fostering; Glean; Goals; Imines; In Situ; Investigation; Ketones; Kilogram; Kinetics; Learning; Ligands; Lithium; Methods; Modeling; N acylation; NMR Spectroscopy; Organic Chemistry; Organic Synthesis; Pathway interactions; Pharmacologic Substance; Play; Process; Property; Reaction; Reagent; Relative (related person); Renaissance; Role; Solutions; Solvents; Staging; Structure; Techniques; Time; Touch sensation; Ursidae Family; base; computational chemistry; drug candidate; drug development; drug synthesis; improved; ketal; lithium diisopropylamide; lithium hexamethyldisilazide

Lithium amides are some of the most important reagents in organic synthesis. The pharmaceutical industry uses these reagents frequently and on very large scales. In this proposal we describe efforts to understand the underlying chemistry of the most important reactions of lithium amides with the goal of improve existing synthetic methods and developing new ones. We continue to focus on the three most important amides: lithium hexamethyldisilazide, lithium diisopropyiamide, and lithium tetramethylpiperidide. The case studies to be investigated include: (1) ketone and ester enolizations; (2) imine lithiations;(3) epoxide eliminations; (4) ortholithiations; (5) N-alkylations; (6) N-arylations; and (7) N-acylations. These case studies touch on the preponderance of the chemistry of lithium amides. Each poses unique questions and offers unique opportunities. Through an understanding of the mechanistic principleswe learn to control reactivity and selectivity. We use a uniquely integrated approach allows a combination of NMR spectroscopy, solution kinetics, and computational chemistry are brought to bear on the problems. By bringing synthetic organic, physical organic, analytical, and computational chemistry together under one roof, we reveal the consequences of soIvation and aggregation with an unprecedented clarity.

氨基锂是有机合成中一些最重要的试剂。制药行业 频繁且大规模地使用这些试剂。在本提案中，我们描述了为理解 氨基化锂最重要反应的基础化学，旨在改善现有的 合成方法和开发新方法。我们继续关注三种最重要的酰胺： 六甲基二硅氮化锂、二异丙酰胺锂和四甲基哌啶锂。案例研究 所研究的内容包括：（1）酮和酯的烯醇化； (2)亚胺锂化；(3)环氧化物消除； (4) 正锂化； (5) N-烷基化； (6) N-芳基化； (7)N-酰化。这些案例研究涉及 氨基锂的化学优势。每个人都提出独特的问题并提供独特的建议 机会。通过理解机械原理，我们学会控制反应性和 选择性。我们使用独特的集成方法，可以将 NMR 光谱、解决方案结合起来 动力学和计算化学被用来解决这些问题。通过引入合成有机物， 物理有机化学、分析化学和计算化学齐聚一堂，我们揭示了 溶剂化和聚集的后果前所未有地清晰。