SYNTHESIS VIA TRANSITION METAL COMPLEXES

新型不对称催化剂的开发 反应是一个重大和长期的挑战。 一边 从相对较少的变化中， 对映选择性可使用轴向不对称 与BINAP相关的双膦，有许多反应，其中 这类化合物只能达到中等水平的对映选择性 的配体。 因此，目前需要新的， 用于不对称合成的同手性双膦的互补类 合成. 本建议的第一部分涉及设计和 三个新的电子和空间“家庭”的合成 差异化的双膦，其中居民手性存在于 磷 在它们的制备之后，这些配体类别将 在Rh（I）催化的不对称变化中进行系统评价 [4 + 2]、[2+2+]和硼氢化反应以及烯烃 通过Ni（0）和Pd（0）催化的氢氰化。 预计该 本文所述的新的纯手性配体将发现许多应用 作为对映体选择性改性剂用于由 过渡金属配合物 在过去三年，首席研究员和他的同事 一直在研究几种新的环化反应介导的 第IV族金属配合物。 在研究过程中，一些 发现了新的偶联反应， 在许多相对简单的模型中， 印刷受体. 本报告第二部分所述研究的重点是 我们的建议将把我们在这一领域的成功经验推广到本集团， IV模板合成几种生物活性靶结构。 感兴趣的分子不仅具有不同的光谱， 药理活性，但也将作为操作模型， 立体、区域和化学控制的关键问题 与IV族介导的偶联过程可以被评估。 作为 根据这项研究的结果，这些新反应对 实现药用重要化合物的实际化学合成 将被揭露。

The development of new asymmetric catalysts for important synthetic reactions constitutes a significant and longstanding challenge. Aside from the relatively few transformations for which impressive enantioselectivities are obtainable using axially dissymmetric bisphosphines related to BINAP, there are numerous reactions in which only modest levels of enantioselection can be achieved with this class of ligands. Accordingly, there is presently a need for new, complementary classes of homochiral bisphosphines for asymmetric synthesis. Part I of this proposal is concerned with the design and synthesis of three new "families" of electronically and sterically differentiated bisphosphines in which the resident chirality exists at phosphorus. Subsequent to their preparation, these ligand classes will be systematically evaluated in asymmetric variations of Rh(I) catalyzed [4 + 2], [2+2+] and hydroboration reactions as well as alkene hydrocyanations catalyzed by Ni(0) and Pd(0). It is expected that the new homochiral ligands described herein will find numerous applications as enantioselective modifiers for other transformations catalyzed by transition metal complexes. Over the past three years, the Principal Investigator and his co-workers have been investigating several new annulation reactions mediated by group IV metal complexes. During the course of these studies, several novel coupling reactions were discovered which proceed with a high degree of chemo and stereoselectivity in many relatively simple model substrates. The focus of the studies described in Part II of this proposal will be the extension of our successes in this area to the group IV templated synthesis of several biologically active target structures. The molecules of interest not only possess a diverse spectrum of pharmacological activities but will also serve as operational models by which the crucial issues of stereo, regio, and chemocontrol associated with group IV mediated coupling processes can be evaluated. As a consequence of this investigation, the utility of these new reactions for effecting practical chemical synthesis of medicinally important compounds will be revealed.