铜催化的自由基不对称 Hiyama C(sp3 )−C(sp2 )交叉偶联反应

过渡金属催化的外消旋烷基卤代烃与芳基/烯基金属试剂的自由基不对称交叉 偶联反应是一类构建手性 C(sp3 )−C(sp2 )键的重要方法。反应的核心策略是利用 3d 过渡金属单电子还原将外消旋烷基卤代烃转化为前手性的烷基自由基，随后手性 金属/亲核试剂络合物与产生的烷基自由基发生相互作用，最终实现手性 C(sp3 )−C(sp2 )键的构建。

本论文首先简要地介绍了过渡金属催化的烷基卤代烃与芳基/烯基金属试剂的 自由基不对称交叉偶联反应，总结并分析了不同金属试剂的特点和该领域的研究 进展。相比于其他有机金属试剂，芳基/烯基硅试剂具有易于制备、化学性质稳定、 官能团兼容性好的优势。但芳基/烯基硅试剂参与的自由基不对称交叉偶联反应却 鲜有报道。因此，利用有机硅试剂作为亲核试剂实现自由基不对称 Hiyama C(sp3 )−C(sp2 )交叉偶联反应具有非常重要的研究意义和实际应用价值。 本论文利用 3d 过渡金属铜作为催化剂，以新型金鸡纳碱衍生的 N,N,N-三齿 亚胺阴离子配体为手性控制源，实现了酰胺 α-位和苄位的自由基不对称 Hiyama C(sp3 )−C(sp2 )交叉偶联反应。在具体研究中，首先对硅试剂的活化试剂进行筛选， 确定了四正丁基铵二氟代三苯基硅酸盐（TBAT）能够在温和条件下促进硅试剂 转金属化。随后对反应中配体的种类进行筛选，发现采用金鸡纳碱衍生 N,N,N-三 齿亚胺阴离子配体不仅提高了铜中心的还原能力，还为不对称反应提供了较优的 立体控制环境，并随后基于该类配体骨架进行改造，从而实现了优秀的手性控制。 之后对反应中铜盐、溶剂等也进行了细致的考察，最终确定了优秀的反应条件。 值得一提的是，此类新型配体尚未报道，具有易于合成和修饰的优点。再者，利 用文献中数据比照的方式，确定了两类手性产物的绝对构型，最后通过对反应历 程的研究，提出了可能的反应机理。

综上，本论文发展了一种铜/新型N,N,N-三齿亚胺阴离子配体催化剂实现了有 机硅试剂与外消旋烷基卤代烃的自由基不对称 Hiyama C(sp3 )−C(sp2 )交叉偶联反应。 该反应不仅条件温和，而且具有良好的底物适用性。烷基卤代物能兼容 α-溴代酰 胺与 α-溴烷基苯，有机硅试剂能兼容芳基硅酯与烯基硅酯，实现了一系列手性化 合物的构建。

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