Chemistry of Lithium Enolates

烯醇锂的化学性质

• 批准号: 8966974
• 负责人: DAVID B. COLLUM
• 金额: $ 2.51万
• 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 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8966974
• 关键词: 3-hydroxybutanal; Address; Alkylation; Amino Acids; Analytical Chemistry; Carbon; Chemistry; Collaborations; Complex; Diamines; Engineering; Esters; Ethers; Goals; Group Processes; Health; Hydroxy Acids; Investigation; Kinetics; Laboratories; Lactams; Lactones; Lithium; Methods; NMR Spectroscopy; Organic Chemistry; Organic Synthesis; Organometallic Chemistry; Oxazolidinones; Pharmacologic Substance; Physical condensation; Play; Process; Reaction; Reagent; Reporting; Research Design; Reverse Transcriptase Inhibitors; Role; Solutions; Solvents; Spectrum Analysis; Structure; Surveys; Temperature; Variant; computational chemistry; dimer; enolate; improved; insight; interest; monomer; programs; scale up; stereochemistry

DESCRIPTION (provided by applicant): Organolithium reagents are used in both academic and industrial laboratories to carry out complex syntheses of medicinally important compounds. The underlying solvent-dependent aggregates and mechanisms of reaction are as complex as in any subdiscipline in organometallic chemistry. We are the only group in the world with expertise in synthetic organic, organometallic, physical organic, analytical, and computational chemistry together in a single laboratory to produce fully integrated studies of structure, mechanism, and selectivity. In this proposal, we continue studies of the chemistry of lithium enolates used prominently to form C-C bonds. The program is fully integrated starting from a synthetic goal, observation, or question. Through a combination of structural and mechanistic studies we answer key questions or offer solutions to key problems. In this proposal we will focus on several classes of enolate that each present unique challenges: (1) We will survey a variety of synthetically important, highly functionalized enolates that remain uncharacterized to date. (2) Lactam and lactone enolates that are central to a collaboration with Pfizer to enhance selectivity in an asymmetric synthesis will serve as templates for evaluating basic structure-reactivity relationships. (3) Oxazolidinone-derived enolates developed by Evans and coworkers will provide basic mechanistic insights into this iconic class of reactive intermediate as well as offer qualitative probes into how structures of heteroaggregates can influence the stereochemistry of functionalizations. (4) Glycinimine-derived enolates offer an especially diverse array of aggregated forms, which will allow us to correlate aggregate structure with mechanism and stereocontrol of functionalizations. (5) ?-allyloxy ester enolates central to [2,3]-sigmatropic rearrangements present both interesting structural challenges and will be investigated to show whether the rearrangement occurs within an aggregate framework. (6) Lithiated amino alkoxides that played vital roles in Merck's and DuPont's asymmetric syntheses of reverse transcriptase inhibitors will be evaluated for their capacity to impart high aggregate control and, in turn, high stereocontrol in reactions of enolates described in the parts 1-5.

描述（由申请人提供）：在学术和工业实验室中使用有机读岩试剂来进行复杂的药物重要化合物。反应的潜在溶剂依赖性聚集体和反应机制与有机金属化学中的任何子学科一样复杂。我们是世界上唯一在单个实验室共同进行合成有机，有机体，分析和计算化学方面具有专业知识的群体，可以对结构，机制和选择性进行完全整合的研究。在此提案中，我们继续研究锂烯醇的化学性质，以形成C-C键。该程序从合成目标，观察或问题开始完全集成。通过结构和机械研究的结合，我们回答关键问题或为关键问题提供解决方案。在此提案中，我们将重点介绍几类方不出一的方不动物：（1）我们将调查迄今为止尚未表征的各种合成重要的，高度功能的烯醇。 （2）与辉瑞合作以提高不对称合成中选择性的核心和内酯烯醇将作为评估基本结构反应关系的模板。 （3）由埃文斯（Evans）和同事开发的黄唑啉酮衍生的烯醇将为这一标志性的反应性中间体提供基本的机械洞察力，并提供定性探测器，以使杂种群的结构如何影响功能化的立体化学化。 （4）糖苷衍生的烯醇化合物提供了一种特别多样的聚合形式，这将使我们能够将聚合结构与机制和功能化的立体控制相关联。 （5）？ - 贝洛克西酯在[2,3] - 含量的重排中心介绍两个有趣的结构挑战，并将研究以显示重排是否发生在聚集框架内。 （6）将评估在默克和杜邦的逆转录酶抑制剂的不对称合成中起着至关重要的作用的岩体烷氧化物，以赋予其赋予高骨料控制的能力，然后赋予高立体控制，并在1-5部分中描述的烯醇反应中高恒定反应。