The Chemistry of Lithium Amides

氨基锂的化学性质

• 批准号: 8055007
• 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/8055007
• 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.

锂酰胺是有机合成中一些最重要的试剂。制药行业 在很大的尺度上使用这些试剂。在此提案中，我们描述了理解的努力 锂酰胺最重要反应的基础化学反应，目的是改善现有 合成方法并开发新方法。我们继续专注于三个最重要的酰胺： 六甲基二硫代锂，二异丙酰胺锂和四甲基哌啶锂。案例研究 被调查包括：（1）酮和酯烯烯； （2）亚胺岩石；（3）环氧消除； （4） 矫正石； （5）N-烷基化； （6）N-包胶； （7）N-酰基化。这些案例研究涉及 锂酰胺化学的优势。每个提出独特的问题并提供独特的问题 机会。通过了解机械原理，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结合NMR光谱，溶液 动力学和计算化学因问题而产生。通过带来合成有机物， 物理有机，分析和计算化学在一个屋顶下一起揭示了 史无前例的清晰度，出现和聚集的后果。