Synthetic Studies of Chiral Organometallics

手性有机金属化合物的合成研究

• 批准号: 6655626
• 负责人: ROBERT E. GAWLEY
• 金额: $ 19.46万
• 依托单位: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6655626
• 关键词: carbanion; chemical stability; chemical structure function; chemical substitution; chemical synthesis; electrochemistry; lithium; molecular rearrangement; nitrogenous heterocyclic compound; nuclear magnetic resonance spectroscopy; organometallic compounds; stereochemistry; tin

Many of today's drugs contain saturated nitrogen heterocyclic rings, thus, it is important to develop new ways to synthesize and modify nitrogen heterocycles. Likewise, it has become important to produce chiral drugs in enantiomerically pure form. For decades, the only stereoselective reactions known to organic chemists were additions of a fourth ligand to heterotopic faces of a trigonal atom. This category includes almost all stereoselective reactions in organic synthesis, and we have accumulated significant insight into the electonic, steric, and dynamic factors that influence these processes. In the past 10 years, significant advances in applying electrophilic substitutions of chiral organometallics (especially organolithiums) as new methods for asymmetric synthesis have been made. This reactivity mode is different from most other asymmetric syntheses in that it involves substitution of a metal attached to a stereogenic carbon atom. Substitution of the metal for an electrophile completes the enantioselective synthesis. Mechanistic understanding of developing methodology is necessary to advancing the field. When contemplating electrophilic substitutions of stereogenic carbanions, one must consider configurational stability, steric course, and aggregation state. If the electrophile is prochiral, two new stereocenters are formed and the question of diastereoselectivity arises. Answering these questions is not always possible; but without answers, mechanistic interpretation is speculative, at best. The specific aims of this project are: 1. To continue our investigation into the scope and limitations of alpha-aminoorganolithium electrophilic substitutions and sigmatropic rearrangements, with emphasis on stereoselectivity in compounds with multiple stereocenters. Explore further extensions of the methodology such as ring-closing metathesis. 2. To develop improved methods of preparation of chiral organometallics. 3. To further explore the solution and solid state structure of chiral organometallics. Evaluate the effects of ligating atoms and metal effects on configurational and structural dynamics of chiral carbanions. 4. To pursue our recent findings relating to possible stereoelectronic effects on transmetalation and the nature of heteroatom participation in tin-lithium exchanges using rapid injection NMR.

当今的许多药物都含有饱和的氮异质环，因此，开发新方法来合成和修饰氮杂环非常重要。 同样，生产对照纯正形式的手性药物也变得很重要。 几十年来，有机化学家已知的唯一立体选择反应是将第四个配体与三角形原子的异位面相加。 该类别几乎包括有机合成中的几乎所有立体选择反应，我们积累了对影响这些过程的选举，空间和动态因素的重大见解。 在过去的10年中，已经做出了用于应用手学有机金属（尤其是有机锂）的亲电替代方案作为不对称合成的新方法的重大进展。 这种反应性模式与大多数其他不对称合成不同，因为它涉及取代与立体碳原子相连的金属。 将金属取代用于电生物可以完成对映选择性合成。对发展方法的机械理解对于推进该领域是必要的。 在考虑立体型碳纤维的亲电替代品时，必须考虑构型稳定性，空间课程和聚集状态。如果亲电器是疗程的，则形成了两个新的立体中心，并且会出现非映射性问题。回答这些问题并非总是可能的；但是没有答案，机械解释充其量是投机性的。 该项目的具体目的是：1。继续我们研究α-氨基氨基岩亲电取代的范围和局限性和乙状结波重排，并重点是具有多个立体化合物的化合物的立体选择性。 探索该方法的进一步扩展，例如闭环归化。 2。开发手性有机金属制备方法的改进方法。 3。进一步探索手性有机金属的溶液和固态结构。 评估连接原子和金属对手性carbanions构型和结构动力学的影响。 4。追求我们最近的发现，涉及使用快速注射NMR参与tin-lithium Confercans的跨金属的可能立体效应和杂原子的性质。