Alkali Metal Chemistry-Structures, Mechanisms, and Applications

摘要和摘要 有机碱金属基试剂在学术上和工业上都有应用 实验室进行具有重要医学价值的化合物的合成。潜在的 聚集体和溶剂化的核心重要性使这些试剂成为 在结构和力学上与有机金属学科中的任何一个分支学科相混淆 化学反应。通过结构和机制研究的结合，我们解决了关键 与反应性和选择性有关的问题。该程序是完全集成的启动 从一个综合的目标、观察或问题出发，通过结构、 机械和计算研究，并以综合有用的见解结束 和方法。将溶剂化视为一种分子现象而不是整体现象是中心 为我们所有的研究。 我们将强调非共价辅助剂的作用，并重点关注两个子集 已经被证明是几乎无法被仔细观察的碱金属化学： 烯醇酸锂和胺化钠。这两个竞技场都需要共同努力，包括(1) 对严重缺乏基本结构和机械原理的说明，以及(2) 推动机制驱动的方法，制定新的控制战略 反应性和选择性。在《寂寞》节目中，我们强调了混合的作用 以手性醇酸锂为载体的聚集体控制相对和绝对 立体化学。在有机钠化学中，我们将继续学习原理 结构和机制来发展完全不存在的反应性和 选择性。在钠基试剂和锂基试剂的众多差异中 到目前为止发现的它是一种催化有机钠与三胺反应的能力。 这一点很突出。我们将重点研究具有催化活性的手性三胺类化合物 钠盐动力学拆分和催化不对称立体控制 得到的碱化中间体的官能化。我们的圣杯是找到 通用添加剂.锂烯醇酸盐用氨基醇氧化物和手性三胺 有机钠反应。

Summary and Abstract Organoalkali metal-based reagents are used in both academic and industrial laboratories to carry out syntheses of medicinally important compounds. The underlying aggregates and central importance of solvation cause these reagents to be as structurally and mechanistically confounding as any subdiscipline in organometallic chemistry. Through a combination of structural and mechanistic studies we address key issues pertaining to reactivity and selectivity. The program is fully integrated starting from a synthetic goal, observation, or question, proceeding through structural, mechanistic, and computational studies, and finishing with synthetically useful insights and methods. Treating solvation as a molecular rather than bulk phenomenon is central to all of our studies. We will emphasize the role of non-covalent auxiliaries and focus on two subsets of alkali metal chemistry that have proven virtually impenetrable to careful scrutiny: lithium enolates and sodium amides. Both arenas require a combined effort involving (1) the elucidation of profoundly lacking basic structural and mechanistic principles, and (2) pushing a mechanism-driven approach to develop new strategies for controlling reactivity and selectivity. In the enolate program, we emphasize the role of mixed aggregates with chiral lithium alkoxides as vehicles to control relative and absolute stereochemistry. In the organosodium chemistry, we will continue studying the principles of structure and mechanism to develop completely absent principles of reactivity and selectivity. Among a multitude of differences of sodium- versus lithium-based reagents discovered so far, it is the capacity to catalyze organosodium reactions with triamines that stands out. We will focus on catalytically active chiral triamines to induce stereocontrol via kinetic resolutions by sodium amides and catalyzed asymmetric functionalizations of the resulting sodiated intermediates. The Holy Grail for us is finding universal additives—amino alkoxides for lithium enolates and chiral triamines for the organosodium reactions.