METALLOIDS IN ASYMMETRIC AND STEREOSELECTIVE SYNTHESIS

不对称和立体选择性合成中的类金属

• 批准号: 3841513
• 负责人: JOHN A SODERQUIST
• 金额: --
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3841513
• 关键词: analytical method; biological products; boranes; chemical substitution; chemical synthesis; drug /agent; metals; nuclear magnetic resonance spectroscopy; organic chemicals; organometallic compounds; organosilicon compound; silanes; stereochemistry

The research proposed herein focuses upon the development of new synthetic methodology which utilizes the special directive properties of metalloidal groups to orchestrate a high degree of control on the stereochemical course which is followed in a given chemical reaction. These principles are examined with respect to classic reactions such as the Wittig olefination, asymmetric hydroboration and the directed aldol condensation. The synthesis of Z-vinylsilanes in high isomeric purity from acylsilane/ylide combinations provides the basis for new routes to trans-alkenol pheromones, and thus, illustrates the novel, complementary role played by acylsilanes compared to aldehydes in the Wittig olefination which give predominately cis products. Extension of this approach to acyltin derivatives should provide access to stereodefined vinyltin compounds which can be converted to one of the chiral aggregation pheromone components of the European elm bark beetle through an asymmetric hydroboration. Moreover, through the asymmetric hydroboration of stereo-defined beta, beta- disubstituted vinylsilanes, a new, general route to optically- active anti-inflammatory agents such as Naproxen, Ibuprofen and six related commercial products is proposed. The approach utilizes the dissymmetry of silyl vs hydrogen substituents at the reaction site to impart diastereofacial selectivity in the process which gives asymmetric induction at the more remote beta carbon. Another aspect of the research takes advantage of several new aspects of stereo-defined silylated vinylboranes which either can be converted to enolboranes which are expected to give threo-selective crossed aldol products with aldehydes, reactions which lead to polyoxygenated antibiotics. On the other hand, new concepts in sterically-directed crossed aldol reactions of acylsilanes either from the standpoint of E-enolates of acylsilanes or from enolate- acylsilane combinations are expected to enhance the scope of the now-general aldol route to these antibiotics. Thus, the thrust of this study is to decisively demonstrate by example the important role that can be played by a metalloidal group in directing the precise course followed in important chemical reactions. Moreover, in the reactions selected for study herein, the basis for further developments will be laid so that the chemical principles learned can be applied to new synthetic targets in the future.

本文提出的研究重点是发展 使用特殊指令的合成方法论 金属群的特性，以精心策划 控制立体化学课程，遵循给定的 化学反应。 对这些原则进行了研究 经典反应，例如Wittig烯烃，不对称 液压和定向醛醇冷凝。 综合 来自酰基/ylide的高异构体纯度的Z-乙烯基硅烷 组合为跨烯醇的新路线提供了基础 信息素，因此说明了小说的互补作用 与维蒂格（Wittig）中的醛相比 烯烃主要赋予CIS产品。 扩展 这种酰基蛋白衍生物的方法应提供 立体置换的乙烯基化合物，可以转换为一种 欧洲榆树的手性聚合信息素成分 树皮甲虫通过不对称的水燃。 而且，通过 立体定义β-β-的不对称水合 取代的乙烯基硅烷，这是一种新的，一般的光学途径 主动抗炎剂，例如萘普生，布洛芬和六种 提出了相关的商业产品。 该方法利用 反应部位的甲硅烷基与氢取代基的不对称 在此过程中赋予非映体选择性 更遥远的β碳的不对称诱导。 其他 研究的各个方面利用了几个新方面 立体定义的用乙烯基乙烯基硼烷可以转换 到有望交叉的Enolboranes 带有醛的藻类产品，导致的反应 多氧抗生素。 另一方面，新概念 酰基烷的空间定向的交叉藻反应 从酰基硅烷的e-烯酸酯的角度或从酸酸的角度来看 酰基硅烷组合有望提高范围 如今，藻类通往这些抗生素。 因此， 这项研究是决定性地证明重要的 金属群可以扮演的角色在指导 重要的化学反应遵循精确的过程。 而且， 在此处选择的研究反应中，这是进一步的基础 开发将被奠定，以便学到的化学原则 将来可以应用于新的合成目标。