The Chemistry of Lithium Amides

氨基锂的化学性质

• 批准号: 7390802
• 负责人: DAVID B. COLLUM
• 金额: $ 31.07万
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7390802
• 关键词: Academia; Acetals; Acids; Age; Alkylation; Amides; Arts; 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; Pharmaceutical Preparations; 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 development; drug synthesis; improved; ketal; lithium diisopropylamide; lithium hexamethyldisilazide

DESCRIPTION (provided by applicant): 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 improving existing synthetic methods and developing new ones. We continue to focus on the three most important amides: lithium hexamethyldisilazide, lithium diisopropylamide, 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 principles we learn to control reactivity and selectivity. We use a uniquely integrated approach allowing a combination of NMR spectroscopy, solution kinetics, and computational chemistry to be 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.

描述（由申请人提供）：锂酰胺是有机合成中一些最重要的试剂。制药行业经常使用这些试剂在很大的尺度上。在这项建议中，我们描述了了解锂酰胺最重要反应的基本化学的努力，目的是改善现有的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：六甲基二甲硅烷，二异丙酰胺锂和四甲基哌啶锂。要研究的案例研究包括：（1）酮和酯的烯醇化； （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。每个都提出了独特的问题并提供了独特的机会。通过了解机械原理，我们学会控制反应性和选择性。我们使用独特的整合方法，允许将NMR光谱，溶液动力学和计算化学的组合结合起来。通过在一个屋顶下将合成有机，物理有机，分析和计算化学反应融合在一起，我们以前所未有的清晰度揭示了出现和聚集的后果。