Stereospecific Cross-Coupling Reactions as a Tool for Three Dimensional Molecular Diversification

项目摘要/摘要 富对映体金属有机亲核试剂在过渡金属催化碳-碳中的应用 键形成反应，我们的目标是开发通用工具来合理操纵三个- 三维分子结构。通过在形成之前引入绝对立体化学 最终的立体中心，并通过立体保持剂或 立体定向交叉偶联过程中，快速制备不同文库的单链- 用于生物分析的候选对映体药物将是可以实现的。对.的使用 富对映体的仲烷基硼和烷基锡烷亲核试剂将在Pd- 和铜催化的烷基-芳基和烷基-烷基交叉偶联反应，特别关注 与药物相关的有机骨架和手性结构基序的衍生化 目前无法获取，但具有生物学或药学价值。

PROJECT SUMMARY/ABSTRACT Using enantioenriched organometallic nucleophiles in transition metal-catalyzed carbon-carbon bond-forming reactions, we aim to develop general tools for the rational manipulation of three- dimensional molecular structure. By introducing absolute stereochemistry prior to the formation of a final stereogenic center, and reliably transferring this stereochemistry via stereoretentive or stereoinvertive cross-coupling processes, the rapid preparation of diverse libraries of single- enantiomer drug candidates for use in biological assays will be achievable. The use of enantioenriched secondary alkylboron and alkylstannane nucleophiles will be explored in Pd- and Cu-catalyzed alkyl-aryl and alkyl-alkyl cross-coupling reactions, with particular focus on the derivatization of medicinally relevant organic frameworks and chiral structural motifs that are currently inaccessible but are of biological or pharmaceutical interest.