Alkali Metal Chemistry-Structures, Mechanisms, and Applications

内容和摘要 有机碱金属基试剂在学术和工业上都有应用 实验室进行重要的药用化合物的合成。底层 聚集体和溶剂化的重要性使这些试剂成为 结构上和机械上的混乱， 化学.通过结构和机制的研究相结合，我们解决关键 与反应性和选择性有关的问题。该计划是完全集成的开始 从一个综合的目标，观察，或问题，通过结构， 机械的，计算的研究，并完成与综合有用的见解 和方法将溶剂化作为一种分子现象而不是整体现象来处理是至关重要的 我们所有的研究。 我们将强调非共价助动词的作用，并集中在两个子集 碱金属的化学性质，已经被证明是几乎无法渗透到仔细审查： 烯醇化锂和氨基钠。这两个领域需要共同努力，包括：（1） 对严重缺乏的基本结构原理和机械原理的阐释;（2） 推动一种机制驱动的方法，以制定新的控制战略， 反应性和选择性。在烯醇化计划中，我们强调混合的作用， 以手性醇锂为载体的聚集体，以控制相对和绝对浓度 立体化学在有机钠化学中，我们将继续研究其原理 的结构和机制，发展完全缺乏反应性的原则， 选择性在钠基试剂与锂基试剂的众多差异中， 迄今为止发现，它是催化有机钠与三胺反应的能力 很突出我们将重点关注催化活性的手性三胺，以诱导 通过氨基钠和催化不对称的动力学拆分的立体控制 所得钠化中间体的官能化。我们的圣杯就是找到 通用添加剂-烯醇化锂的氨基醇盐和 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.