SYNTHESIS VIA TRANSITION METAL COMPLEXES

重要合成用新型不对称催化剂的研究进展 反应是一项重大而长期的挑战。搁置一边 从相对较少的令人印象深刻的转变 利用轴向不对称可以获得对映体选择性。 与BINAP相关的双膦，有许多反应，其中 这个职业只能达到适度的对映体选择性。 配位体。因此，目前需要新的、 不对称同手性双膦配体的互补类 综合。本建议书的第一部分是关于设计和 三个新的电子和立体“家族”的合成 驻留手性存在的区别双膦 磷。在准备好之后，这些配基课程将 被系统评价在Rh(I)催化的不对称变异中 [4+2]、[2+2+]和硼氢化反应以及烯烃 Ni(0)和Pd(0)催化的氢氰化反应。预计将会有 这里描述的新的同手性配体将会有很多的应用 作为催化其他转化的对映体选择性修饰剂 过渡金属络合物。 在过去三年，首席调查员和他的同事 一直在研究几种新的环化反应，这些反应由 第IV族金属络合物。在这些研究过程中，有几个 发现了新的高度进行的偶联反应 在许多相对简单的模型中的化学和立体选择性 底物。本部分第二部分所述研究的重点 提案将是我们在这一领域的成功延伸到集团 IV几种生物活性目标结构的模板化合成。 感兴趣的分子不仅拥有不同的光谱 药理活动，但也将作为业务模式，由 与立体声、区域和化学控制等关键问题相关的 对于IV组介导的偶联过程可以进行评估。作为一名 这项调查的结果，这些新反应对 影响重要药用化合物的实用化学合成 将会被揭晓。

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.