STEREOCHEMISTRY OF A CARBON-CARBON BOND-FORMING PROCESS

碳-碳键形成过程的立体化学

• 批准号: 3296519
• 负责人: JOHN D BUYNAK
• 金额: $ 5.16万
• 依托单位: SOUTHERN METHODIST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3296519
• 关键词: alkyl group; carbon; carboxylate; catalyst; chemical bond; drug design /synthesis /production; silanes; silicon; stereochemistry

The thermolysis of alpha-silylalkyl carboxylates results in the 1,2- migration of an unactivated alkyl group from silicon to carbon accompanied by a reverse migration of carboxylate. This extremely efficient rearrangement occurs at temperatures between 100 and 250 degrees C. The stereospecificity of this reaction will be investigated with the goal of developing a synthetically useful process for the formation of carbon-carbon bonds. Such processes are crucial to the preparation of biologically active materials. The reaction possesses several advantages over other dipolar or boron-mediated methods for the formation of carbon-carbon bonds: 1) It occurs under extremely mild conditions, without strong bases or acids; 2) The silicon atom provides a convenient, disposable handle to direct the formation of chirality in the alkyl fragments; 3) Since neither carbon fragment must undergo conversion to a highly reactive species (such as a carbanion), both centers should remain chiral (through either inversion or retention of configuration), thus allowing the stereospecific joining of two carbon atoms without the need for a chiral auxiliary; 4) The large number of ways for the formation of carbon-silicon bonds will permit the application of this methodology to the preparation of a variety of systems. Absolute chirality will be created at the migratory and terminal carbon atoms as well as at silicon. Chirality at the terminal, oxygen-bearing, carbon will be introduced by the reduction of acyl silanes with chiral borolane reagents. The resultant chiral silylcarbinols will also be evaluated as synthetic precursors to currently inaccessible chiral alcohols via both intra- and intermolecular processes. Chirality at the migratory carbon atom will be introduced by the reaction of silyl anions with the tosylates of available chiral alcohols. Silanes which are chiral at silicon will be prepared through stereospecific transformations of (+)-alpha-naphthylmethylphenylsilane.

α-甲硅烷基烷基羧酸酯的热分解产生1，2-甲硅烷基羧酸酯。 未活化的烷基从硅向碳的迁移 伴随着羧酸盐的反向迁移。 这 在一定的温度下， 在100到250摄氏度之间。 这种立体专一性 反应将进行研究，目的是开发一种 用于形成碳-碳的合成有用的方法 债券 这些过程对于制备 生物活性物质。 该反应具有优于其它偶极或偶极反应的几个优点。 用于形成碳-碳的硼介导方法 （1）它发生在极其温和的条件下， 强碱或酸; 2）硅原子提供了方便的， 一次性手柄，以指导烷基中手性的形成 （3）由于碳碎片不需要 转化为高反应性物质（如碳负离子）， 中心应保持手性（通过反转或保留 的构型），从而允许两个分子的立体特异性连接。 不需要手性助剂; 4）大的 形成碳-硅键的许多方法将 允许将这一方法应用于编制一份 各种系统。 绝对手性将在迁移和末端产生 碳原子以及硅原子。 末端的手性， 含氧，碳将通过还原酰基 硅烷与手性硼杂环戊烷试剂。 所得手性 甲硅烷基甲醇也将作为合成前体进行评价， 目前无法通过内和外两种途径获得的手性醇 分子间过程 迁移碳原子的手性 将通过甲硅烷基阴离子与 可用手性醇的甲苯磺酸酯。 手性硅烷， 硅将通过以下物质的立体定向转化来制备： （+）-α-萘基甲基苯基硅烷。