FINE TUNING BINOLS AND BINAPS FOR ASYMMETRIC SYNTHESIS

描述：(申请人摘要)在不对称合成领域， 最有效的方法之一涉及使用BINOL和BINAP配体 作为催化剂。这些两栖类物种是分布最广泛的 用于将手性诱导到大量中间体中的系统 在获得生理活性化合物的过程中具有重要价值。他们参与了 如萘普生(抗炎)、吗啡(麻醉剂)和 右美沙芬(止咳药)只是开始接触他们的 对制药领域的重要性，现在大多数新药都必须 “手性”(即单一对映体)。然而，值得注意的是，只有极少数 已知被替换的BINOL，但没有被替换的BINAP，其中任何 在萘环上的剩余位置上含有可能 显著提高了许多依赖于 这些配体中的一种。因此，这项提案试图解决这一问题 根本问题；也就是提供方法论以达到 取代的BINOL和BINAP。特别是，在3-和 3，3‘-职位将得到解决，因为这些网站可以在 通过立体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 在单个过敏成分附着到非外消旋体上时 系绳，随后分子内氧化联芳基偶联到 相应的光学纯的取代环-BINOL阵列。来自配体 这种类型带来了更多的选择，例如聚合物的机会 安装，并可能最受关注，转换为替代 Cyclo BINAPs。

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.