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

项目总结/摘要 在过渡金属催化的碳-碳反应中使用对映体富集的有机金属亲核试剂 键形成反应，我们的目标是开发一般的工具，合理操纵三个- 三维分子结构通过在形成前引入绝对立体化学， 的最终立体异构中心，并可靠地通过立体保留或 立体转化交叉偶联过程，快速制备不同的单- 用于生物测定的对映异构体药物候选物将是可实现的。使用 对映体富集的仲烷基硼和烷基锡烷亲核试剂将在Pd- 和Cu催化的烷基-芳基和烷基-烷基交叉偶联反应，特别关注 药物相关的有机框架和手性结构基序的衍生化， 目前无法获得，但具有生物学或药学意义。

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.