ANTI-INFLAMMATORY AGENTS, ANTIBIOTICS AND PHEROMONES VIA VINYL METALLOIDS

本文提出的研究重点是开发新的 综合方法，利用特殊指令 类金属基团的性质，以协调高度的 控制在给定的立体化学过程中遵循的立体化学过程， 化学反应 这些原则将在以下方面进行审查： 经典反应如Wittig烯化、不对称 硼氢化和直接羟醛缩合。 合成 从酰基硅烷/叶立德制备高异构体纯度的Z-乙烯基硅烷 组合为反式烯醇的新途径提供了基础 费洛蒙，因此，说明了新的，互补的作用， 与维蒂希的醛相比， 烯化反应主要产生顺式产物。 延长 这种获得酰基锡衍生物的方法应该能够提供 立体定向的乙烯基锡化合物，其可以转化为以下之一： 欧洲榆树的手性聚集信息素成分 树皮甲虫通过不对称硼氢化反应。 而且通过 立体定向的β，β- 二取代的乙烯基硅烷，一种新的，通用的路线，以光学- 活性抗炎剂，如萘普生，伊诺明和六 提出了相关的商业产品。 该方法利用了 反应位点上硅基对氢取代基的不对称性 以在该方法中赋予非对映体选择性， 在更远的β碳上的不对称诱导。 另一 研究的一个方面利用了几个新的方面， 立体限定的甲硅烷基化乙烯基硼烷，其可以被转化为 到烯醇硼烷，其预期给出苏式选择性交叉 醛醇产物与醛的反应， 多氧抗生素 另一方面， 酰基硅烷的空间定向交叉羟醛缩合反应， 从酰基硅烷的E-烯醇化物或从烯醇化物的观点来看， 预期酰基硅烷组合物将增强本发明的范围。 现在一般羟醛途径这些抗生素。 因此， 这项研究是决定性的示范的重要性， 类金属基团可以在引导 在重要的化学反应中遵循精确的路线。 此外，委员会认为， 在本文选择用于研究的反应中，进一步 将进行开发，以便学习化学原理 在未来可以应用于新的合成目标。

The research proposed herein focuses upon the development of new synthetic methodology which utilizes the special directive properties of metalloidal groups to orchestrate a high degree of control on the stereochemical course which is followed in a given chemical reaction. These principles are examined with respect to classic reactions such as the Wittig olefination, asymmetric hydroboration and the directed aldol condensation. The synthesis of Z-vinylsilanes in high isomeric purity from acylsilane/ylide combinations provides the basis for new routes to trans-alkenol pheromones, and thus, illustrates the novel, complementary role played by acylsilanes compared to aldehydes in the Wittig olefination which give predominately cis products. Extension of this approach to acyltin derivatives should provide access to stereodefined vinyltin compounds which can be converted to one of the chiral aggregation pheromone components of the European elm bark beetle through an asymmetric hydroboration. Moreover, through the asymmetric hydroboration of stereo-defined beta, beta- disubstituted vinylsilanes, a new, general route to optically- active anti-inflammatory agents such as Naproxen, Ibuprofen and six related commercial products is proposed. The approach utilizes the dissymmetry of silyl vs hydrogen substituents at the reaction site to impart diastereofacial selectivity in the process which gives asymmetric induction at the more remote beta carbon. Another aspect of the research takes advantage of several new aspects of stereo-defined silylated vinylboranes which either can be converted to enolboranes which are expected to give threo-selective crossed aldol products with aldehydes, reactions which lead to polyoxygenated antibiotics. On the other hand, new concepts in sterically-directed crossed aldol reactions of acylsilanes either from the standpoint of E-enolates of acylsilanes or from enolate- acylsilane combinations are expected to enhance the scope of the now-general aldol route to these antibiotics. Thus, the thrust of this study is to decisively demonstrate by example the important role that can be played by a metalloidal group in directing the precise course followed in important chemical reactions. Moreover, in the reactions selected for study herein, the basis for further developments will be laid so that the chemical principles learned can be applied to new synthetic targets in the future.