多取代环己炔及环己联烯前体的制备、构效关系与合成应用研究

虽然苯炔化学过去几十年来取得了很大发展，但作为与苯炔对应的环己炔及环己联烯仅有较少报道，而环己烷结构广泛存在于自然界及药物分子中。因此，系统研究这类高活性中间体的反应性规律，并开发它们对含多取代环己烷结构的天然产物及生物活性分子的合成应用，具有重要的科学意义。本申请计划分三个层次,以依次递进的方式，逐步深入地探索多取代环己炔及环己联烯的前体制备、构效关系及合成应用。首先，本申请提出通过多种苯环去芳构化手段，制备多取代环己炔及环己联烯前体的设计方案。其次，申请人计划利用获得的这些多取代活性中间体去研究它们的构效关系，总结它们在生成、稳定性、反应性、区域选择性及反应类型适用性中的一般规律，并发掘它们的合成应用。最后，探索与开发上述脂肪族活性中间体区别于传统苯炔化学的新反应模式，开发其新的串联反应过程。若能实现上述设计方案，可大幅推进环己炔及环己联烯领域的发展，具有重要意义。

Although benzyne chemistry has gained giant development in the past a few decades, its analogous aliphatic hexatomic cyclic active intermediates, namely cyclohexyne and cyclohexallene, only received sporadic attention, despite the fact that cyclohexane frameworks broadly exist in nature and drug molecules. Consequently, it owns essential scientific merits in terms of systematic exploring the reaction behavior of these intermediates as well as applying them in the preparation of natural products and bioactive molecules. In this proposal, there are three levels of study plan in our aim to explore the preparation, reactivity, and synthetic applications of those multisubstituted active species: first, we propose to use diverse dearomatization approaches to reach various substituted target intermediate precursors; second, with those precursors in hand, we plan to study the structure-activity relationship (SAR) in the presence of those substituents, which in turn would provide a chance to learn the rules to tune their generation, stability, reactivity, regioselectivity, and compatibility with different types of reactions; last but not the least, exploring and developing new reaction patterns and cascade processes of cyclohexyne/cyclohexallene, differentiating from traditional benzyne chemistry, is our another goal. Once the above proposals could be realized, these studies would greatly propel the growth of cyclohexyne/cyclohexallene chemistry, and hence owns important scientific value.