The Use of Optically-Active Nucleophiles in Metal-Catalyzed Coupling Reactions

描述（由申请人提供）：我们的目标是通过在过渡金属催化的碳-碳键形成反应中使用光学活性有机金属亲核试剂来生产非外消旋生物活性分子。通过在形成最终所需键之前建立立体中心，将可实现用于生物测定的单一对映体候选药物的多种文库的快速制备。光学活性二级亲核试剂的使用将首先在烷基-芳基交叉偶联反应中进行探索，并扩展到光学活性三级亲核试剂的使用。烷基硼试剂和烷基氮杂锡纳烷试剂构成了本研究中涉及的主要亲核试剂。虽然这项工作的主要重点是钯和镍催化系统，使用铜和银催化也将进行调查。我们的立体保留交叉偶联反应将扩展到碳-杂原子键的构建，以最大限度地获得目前无法获得但具有生物学或药学意义的手性结构基序。

DESCRIPTION (provided by applicant): We aim to produce non-racemic biologically active molecules by employing optically active organometallic nucleophiles in transition metal-catalyzed carbon-carbon bond- forming reactions. By establishing the stereogenic center prior to the formation of the final desired bond, the rapid preparation of diverse libraries of single-enantiomer drug candidates for use in biologic assays will be achievable. The use of optically active secondary nucleophiles will be initially explored in alkyl-aryl cross-coupling reactions, an extended to the use of optically active tertiary nucleophiles. Alkylboron and alkyl azastannatrane reagents constitute the main nucleophiles involved in this study. Although the major focus of this work is on palladium- and nickel-catalyzed systems, the use of copper and silver catalysis will also be investigated. Our stereoretentive cross- coupling reactions will be extended to the construction of carbon-heteroatom bonds in order to maximize access to chiral structural motifs that are currently inaccessible but are of biological or pharmaceutical interest.