FINE TUNING BINOLS AND BINAPS FOR ASYMMETRIC SYNTHESIS

微调 BINOL 和 BINAPS 以进行不对称合成

• 批准号: 2857322
• 负责人: BRUCE H. LIPSHUTZ
• 金额: $ 20.32万
• 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/2857322
• 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.

说明：（申请人摘要）在不对称合成领域， 最有效的方法之一是使用BINOL和BINAP配体 作为催化剂。 这些联萘物种是最广泛的 用于将手性引入大量中间体的系统 有价值的生理活性化合物。 他们参与 这些靶点如萘普生（抗炎药）、吗啡（麻醉药）， 美沙芬（咳嗽抑制剂）只是开始触及他们的 对制药竞技场的重要性，大多数新药现在必须 “手性”（即，单一对映体）。 然而，值得注意的是， 已知的替代BINOL，没有替代BINAP，其中任何 萘环上的剩余位置带有可能 显著改善了依赖于 这些配体之一。 因此，这项建议旨在解决这一问题。 基本问题;即提供方法， 替代BINOL和BINAP。 特别地，在3-和 3，3 '-位置将得到解决，因为这些网站可以发挥关键作用， 通过空间因子增强非外消旋联萘诱导的立体诱导 和/或螯合性能。 提供这种新配体的关键在于 在将各个萘环组分连接到非外消旋 系链，随后分子内氧化联芳基偶联至 相应的，光学纯的，取代的环-BINOL阵列。 从配体 这种类型带来了进一步的选择，例如聚合物的机会 安装，并可能最大的关注，转换为替代 环BINAP。