Stereospecific cross-coupling reactions as a tool for three-dimensional molecular diversification

项目摘要/摘要 在钯催化的碳-碳键中使用富对映体金属有机亲核试剂-- 形成反应，我们的目标是开发快速制备非外消旋的通用工具 生物活性分子。通过建立最终的立体构型在 最终形成所需的键，快速制备不同的单链文库- 用于生物分析的候选对映体药物将是可以实现的。光学的使用 活性的仲烷基硼和烷基锡烷亲核试剂将首先在Pd- 催化的烷基-芳基交叉偶联反应，特别关注 与医学相关的有机框架。中将强调杂环的包含。 以便最大限度地获得手性结构基序，这些基序目前无法访问，但 生物或医药方面的利益。

PROJECT SUMMARY/ABSTRACT Using enantioenriched organometallic nucleophiles in palladium-catalyzed carbon-carbon bond- forming reactions, we aim to develop general tools for the rapid preparation of non-racemic biologically active molecules. By establishing the final stereogenic configuration prior to the formation of the final desired bond, the rapid preparation of diverse libraries of single- enantiomer drug candidates for use in biological assays will be achievable. The use of optically active secondary alkylboron and alkylstannane nucleophiles will initially be explored in Pd- catalyzed alkyl-aryl cross-coupling reactions, with particular focus on the derivatization of medicinally relevant organic frameworks. The inclusion of heterocycles will be emphasized in order to maximize access to chiral structural motifs that are currently inaccessible but are of biological or pharmaceutical interest.