FINE TUNING BINOLS AND BINAPS FOR ASYMMETRIC SYNTHESIS

微调 BINOL 和 BINAPS 以进行不对称合成

• 批准号: 6138596
• 负责人: BRUCE H. LIPSHUTZ
• 金额: $ 20.71万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6138596
• 关键词: chemical structure function; chemical substitution; chemical synthesis; chromatography; drug design /synthesis /production; ligands; mass spectrometry; method development; naphthalenes; nuclear magnetic resonance spectroscopy; stereoisomer

DESCRIPTION: (applicant's abstract) In the field of asymmetric synthesis, one of the most powerful approaches involves use of BINOL and BINAP ligands as catalysts. These binaphthylic species are among the most extensively utilized systems for inducing chirality into a vast array of intermediates of value en route to physiologically active compounds. Their involvement in such targets as naproxen (anti-inflammatory), morphine (narcotic), and dextromethorphan (cough suppressant) only begin to touch upon their importance to the pharmaceutical arena, where most new drugs must now be "chiral" (i.e., single enantiomer). Remarkably, however, there are very few substituted BINOLs known, and no substituted BINAPs, where any of the remaining positions on the naphthalene rings bear groups that might significantly improve enantioselectivity of numerous reactions which rely on one of these ligands. This proposal, therefore, seeks to address this fundamental problem; that is, of supplying methodology for arriving at substituted BINOLs and BINAPs. In particular, substitution at the 3- and 3,3'-positions will be addressed, as these sites can play a pivotal role in enhancing nonracemic binaphthyl-induced stereoinduction via steric factors and/or chelation properties. The key to providing such new ligands rests upon the attachment of the individual naphythylic components to a nonracemic tether, with subsequent intramolecular oxidative biaryl coupling to the corresponding, optically pure, substituted cyclo-BINOL array. From ligands of this type come further options, such as opportunities for polymer mounting, and potentially of greatest attention, conversion to substituted cyclo BINAPs.

描述：（申请人的摘要）在不对称合成领域， 最有力的方法之一是使用Binol和Binap配体 作为催化剂。 这些双珠物种是最广泛的 利用系统将手性诱导成各种各样的中间体 在生理活性化合物的途中的价值。 他们参与 萘普生（抗炎），吗啡（麻醉剂）和 右美甲苯克（咳嗽抑制剂）才开始触摸 对于药品领域的重要性，现在大多数新药都必须是 “手性”（即单个对映异构体）。 但是，很少有人很少 已知的替换Binols，没有取代的Binaps，其中任何一个 萘环上的剩余位置可能 显着提高依赖众多反应的对映选择性 这些配体之一。 因此，该提议试图解决这个问题 基本问题；也就是说，提供用于到达的方法 取代的Binols和Binaps。 特别是，在3和3和 将解决3,3'位置，因为这些站点可以在 通过空间因子增强非种族歧视双酰胺诱导的立体诱导 和/或螯合特性。 提供此类新配体的关键是休息 在依附于单个的月经成分对非流行病学上 系绳，随后分子内氧化双轴偶联 相应的，光学纯的，取代的Cyclo-Binol阵列。 来自配体 这种类型的选择，例如聚合物的机会 安装，并有可能受到最大的关注，转换为取代 Cyclo Binaps。