钯催化的不对称亚胺基化反应研究

Due to the strong coordinating ability of isocyanide to metal centers in competing with chiral ligands, palladium-catalyzed asymmetric isocyanide insertion, also known as asymmetric imidoylation, is a challenging issue and only few examples were reported with moderate enantioselecivities. This research proposal aims to develop highly efficient method for the construction of structurally diversified chiral heterocycles through palladium-catalyzed isocyanide insertion under the control of chiral ligand as a key step, followed by annulation with various functionalities inbuilt in isocyanide. By adopting this strategy, the competition of isocyanides and chiral ligands with palladium intermediate could be inhibited effectively, and the types of chiral heterocycles constructed could be fruitful. This enantioselective imidoylative annulation reaction has been successfully applied to the synthesis of central-chiral and planar-chiral heterocycles. Baesd on these results and our experiences on isocyanide chemistry, the scope of the functionalized isocyanides and palladium(II) species will be fully explored. This research proposal could provide new synthetic methods for the construction of chiral heterocycles.

由于异腈与过渡金属的强配位能力，在不对称催化过程中会与手性配体和金属中心的配位发生竞争，因此通过手性配体调控的不对称异腈插入反应，即不对称亚胺基化反应，是一项挑战性的课题，目前成功的例子很少，而且对映选择性不高。本研究计划以各种官能化的异腈为研究对象，通过钯催化的异腈迁移插入为关键步骤，形成的亚胺基钯中间体在手性配体的调控下再选择性地与分子内的各种官能团反应关环，从而构建各种手性杂环化合物。采用这一策略，不仅可以有效抑制异腈基团和手性配体与钯中间体的配位竞争，而且可以极大地丰富所构建的手性杂环种类。在已成功实现了几类中心手性、平面手性杂环化合物的构建的基础上，我们将进一步拓展官能化异腈的种类，为各种手性杂环的构建提供新的合成方法。

本项目在执行期间，按照原计划进行，使用官能化异腈的策略，通过钯催化的异腈迁移插入为关键步骤，形成的亚胺基钯中间体在手性配体的调控下再选择性地与分子内的各种官能团反应关环，从而构建各种手性杂环化合物。采用这一策略，不仅可以有效抑制异腈基团和手性配体与钯中间体的配位竞争，而且可以极大地丰富所构建的手性杂环种类。利用这一策略我们已成功合成了多种多样的手性杂环化合物，实现了中心手性、平面手性、轴手性和固有手性杂环化合物的高效合成，具体的研究内容包括：（1）通过钯催化的不对称亚胺基化环化反应高对映选择性构建平面手性二茂铁化合物；（2）通过钯催化的不对称Heck/羰基环化反应，构建手性氧化吲哚螺环类化合物；（3）实现了钯催化的多米诺亚胺化/Heck反应/C–H活化反应，通过异腈接力策略构建含有全碳季碳中心的稠杂环；（4）通过官能化异腈的策略实现了钯催化的不对称亚胺基环化反应构建轴手性化合物；（5）通过双异腈连续插入策略实现了钯催化的不对称亚胺基环化反应构建固有手性八元氮杂环；（6）实现了钯催化的含有非活化烯烃的官能化异腈的四组分串联亚胺基-甲氨酰化反应。项目共发表SCI论文12篇，申请中国发明专利2项。