Chemistry of Lithium Enolates

描述（由申请人提供）：有机锂试剂用于学术和工业实验室，以进行医学重要化合物的复杂合成。潜在的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。我们是世界上唯一一个在合成有机，有机金属，物理有机，分析和计算化学方面拥有专业知识的团队，在一个实验室中进行结构，机制和选择性的全面综合研究。在这个建议中，我们继续研究的锂烯醇化物的化学突出用于形成C-C键。该计划从一个综合目标，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提供关键问题的解决方案。在这个建议中，我们将集中在几个类别的烯醇化物，每一个提出独特的挑战：（1）我们将调查各种合成重要的，高度官能化的烯醇化物，至今仍未确定。(2)内酰胺和内酯烯醇化物是与辉瑞公司合作的核心，以提高不对称合成的选择性，将作为评估基本结构-反应性关系的模板。(3)由Evans及其同事开发的恶唑烷酮衍生的烯醇化物将为这类标志性的反应中间体提供基本的机械见解，并为杂聚集体的结构如何影响官能化的立体化学提供定性探针。(4)甘氨酸衍生的烯醇化物提供了特别多样化的聚集形式，这将使我们能够将聚集体结构与官能化的机制和立体控制相关联。(5) ?-对[2，3]-σ迁移重排起中心作用的烯丙氧基酯烯醇化物提出了有趣的结构挑战，并将被研究以显示重排是否发生在聚集体框架内。(6)将评价在Merck和DuPont逆转录酶抑制剂的不对称合成中发挥重要作用的锂化氨基醇盐赋予高度聚集体控制的能力，进而评价其在第1-5部分中描述的烯醇化物反应中赋予高度立体控制的能力。

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.