Chemistry of Lithium Enolates

烯醇锂的化学性质

• 批准号: 7617824
• 负责人: DAVID B. COLLUM
• 金额: $ 29万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7617824
• 关键词: Acylation; Alkylation; Amides; Antithrombin III; Case Study; Chemistry; Collaborations; Drug Industry; Esters; Funding; Investigation; Ketones; Kinetics; Learning; Lithium; Methods; Modeling; NMR Spectroscopy; Occupations; Organic Synthesis; Oxazolidinones; Physical condensation; Preparation; Reaction; Reagent; Reporting; Salts; Solutions; Structure; Variant; base; computational chemistry

DESCRIPTION (provided by applicant): Lithium enolates constitute one of the most important classes of reactive intermediate 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 enolates. We will focus on ascertaining key structure-reactivity relationships for a number of enolates including enolates derived from simple esters and ketones, beta-amino-esters, chiral carboxamides based on oxazolidinone and ephedrate auxiliaries (Evans and Myers enolates), N-methoxycarboxamides (Weinreb amides), and alpha fluoro esters. The lithium salts of chiral vicinal amino alkoxides will also be investigated. Given the limited progress toward understanding solution structures of lithium enolates reported to date, considerable effort will focus on developing and refining new methods of structure determination. The relationships of structure and reactivity will derive from case studies to be investigated including (1) alkylation, (2) acylation, (3) azaaldol condensation, and (4) nucleophilic aromatic substitution. Through an understanding of the mechanistic principles we learn to control reactivity and selectivity via a uniquely integrated approach based on a combination of NMR spectroscopy, solution kinetics, and computational chemistry. By bringing synthetic organic, physical organic, analytical, and computational chemistry together under one roof, we reveal the consequences of solvation and aggregation with an unprecedented clarity.

描述（由申请人提供）：锂烯醇构成有机合成中最重要的反应性中间体之一。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，我们描述了了解锂烯醇最重要反应的基本化学的努力。 We will focus on ascertaining key structure-reactivity relationships for a number of enolates including enolates derived from simple esters and ketones, beta-amino-esters, chiral carboxamides based on oxazolidinone and ephedrate auxiliaries (Evans and Myers enolates), N-methoxycarboxamides (Weinreb amides), and alpha fluoro esters.还将研究手性氨基烷氧化物的锂盐。鉴于迄今为止报告的锂烯醇的解决方案结构的进展有限，因此大量努力将集中在开发和完善新的结构确定方法上。结构和反应性的关系将源自案例研究，包括（1）烷基化，（2）酰化，（3）偶氮二醇凝结和（4）亲核芳香族芳族取代。通过了解机械原理，我们学会通过基于NMR光谱，溶液动力学和计算化学的组合来通过唯一集成的方法来控制反应性和选择性。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溶剂化和聚集的后果。