金属催化的杂环化合物碳氢键选择性烷基化反应研究

Heterocyclic compounds, of which synthesis and application have intrigued numerous chemists, are the important part of organic compounds. Among a variety of reported methods of alkyl-substituted heterocyclic compounds, the transition-metal catalyzed direct alkylation reactions of C-H bond have been developed rapidly in the past ten years because of the high atom-economy. However, there are some problems remain to be solved. This project will employ diacyl peroxides as alkylation reagents to explore the metal catalyzed C-H bond selective alkylation of five- or six-membered heteroaromatic compounds and five- or six-membered saturated heterocyclic compounds. Furthermore, the regioselective alkylation of the above-mentioned heterocyclic compounds and the enantioselective alkylation of the saturated heterocyclic compounds will be realized. The diacyl peroxides could simultaneously be used as alkylation reagents and oxidants, which might afford the mild reaction conditions. The success of this project will not only expand the kind of heterocyclic compounds and realize the regioselectivity and enantioselectivity of products in the alkylation reactions, but also provide a new approach for the alkylation of heterocyclic compounds.

杂环化合物是有机化合物的重要组成部分，其应用和合成受到化学家们的广泛关注。合成烷基取代的杂环化合物的方法有多种，其中，过渡金属催化的杂环化合物碳氢键直接烷基化因反应原子经济性而受到青睐，近十年来发展迅速，多个催化体系被发展出来。尽管如此，杂环的直接烷基化反应还存在众多的待解难题。本课题将采用酰基过氧化物作为烷基化试剂，探索金属催化的芳香五元杂环、六元杂环、饱和五元杂环和饱和六元杂环等的直接烷基化反应，以期实现如上众杂环的区域选择性烷基化，和饱和杂环的立体选择性烷基化反应。酰基过氧化物既可以作为烷基化试剂，也可作为氧化剂，有可能帮助实现温和条件下的烷基化反应。通过本课题的研究，希望可以拓宽杂环烷基化反应中杂环的种类，实现杂环烷基化的区域及立体选择性，最终建立杂环烷基化的通用方法。

本项目利用烷基过氧化物，既作氧化剂，又作烷基化试剂，发展了多个简单、高效、经济的催化体系。不仅实现了杂芳环化合物的选择性烷基化反应，还建立了一系列不饱和键的烷基化反应，极大扩展了我们对烷基过氧化物的传统认识。此外，本项目采用廉价的过渡金属或布朗斯特酸分别为催化剂或促进剂，在温和、绿色的条件下建立了烷基过氧化物作烷基化试剂的反应体系，合成了多种烷基取代的杂芳环、烷基取代的胺类和醚类、烷基取代的烯烃类等化合物。合成的多种类烷基化合物可作为有机合成中间体，或有潜在生理活性的药物中间体。经研究发现，反应的机理均涉及烷基自由基接力过程。