基于枞酸等萜烯的光诱导环加成反应构建含张力小环多环体系的立体选择性调控研究

Photoinduced reactions are cleaner and more energy saving than traditional reactions, which also could lead to diversity-oriented syntheses even from the same starting material. The photocycloaddition(PCA) plays an important role in constructing molecules with strain rings. However, the stereo- selectivities are hard to control in these reactions because it will generate up to three or more chiral centers in one reaction. And some good reactions are completely limited in a small range of specific substrates. Since the fact of the native chirality and rigid structure with three fused rings of the natural terepenoid, it will benefit the enatioselectivity of the photoreaction. In this proposal, we plan to carry out the photo-induced [1+2] and [2+2] cycloaddition to obtain complicated polycyclic compounds which are fused with a strained three- or four-membered ring from the natural terpenoid and diazirine or enones.We plan to adjust the enatio-selectivity by solid state photochemistry, hydrogen bonding templated host-guest interaction and visible light driving photoredox reactions in the presence of a Lewis acid as cocatalyst to obtain specific configuration product. After further investigation of the mechanisms for the reaction by experimental and theoretical study, we could find a reasonable way to get the control of an asymmetrical photocycloaddition. It will be helpful both to enlarge the scope of enatioselcetive photoreactions and also to synthesize complicated polycyclic natural products.

光化学合成具有清洁、节能等诸多优点，从同一分子出发可以获得丰富的合成产物，从而实现多样性合成。光化学环加成反应是构建含张力小环分子体系的重要手段，但是对同时构成多个手性中心的立体选择性进行调控的手段和适用底物结构的稀缺使这一方法的应用受到很多限制。天然萜类化合物具有手性诱导作用和刚性的骨架结构，作为底物在获得高不对称选择性的光化学反应方面具备很好的优势。本项目以松香树脂酸主要成分枞酸为底物，与diazirine和烯酮类化合物进行光诱导下的[1+2]或[2+2]环加成反应来合成含有3,4元环稠合的多环化合物，采用晶体光化学、氢键络合物诱导和Lewis酸促进的可见光反应等手段对反应的立体选择性进行调控。在此基础上，结合实验和理论计算研究相关反应的机理，以获得高选择性的光化学合成方法。项目研究不仅是对不对称有机光反应的重要拓展和补充，而且可以进一步发展成为复杂多环天然产物的合成方法。

本项目的执行过程中，主要发现了一些基于光诱导反应和热反应的环化反应，以及在发展这些反应方法中对所需原料的合成方法也做了一些探索：(1)探索了苯基卤代卡宾与松香树脂酸中枞酸甲酯的环丙烷化反应，并初步探索了反应机制，深入的机理研究和此高速率的环化反应选择性控制正在进行。在此过程中，发展了基于LiOH催化下，使用碳酸二甲酯对于枞酸高效甲酯化反应。（2）发展了3,4-二氯香豆素与丁二烯类化合物的光-热-光一锅法制备具有优良生物活性的二苯并吡喃酮化合物的方法，并对于其中的己三烯中间体进行了分离纯化，获得了较多的机理方面的认识。（3）对于芳杂环化合物的卤化反应也进行了探索，发展了以卤化铜、卤化锌等Lewis酸催化对于N-卤代丁二酰亚胺的活化作用，并将之用在香豆素、黄酮和补骨脂素等缺电子杂环化合物的亲电卤化反应上。（4）此外还发展了两类杂环化合物，即苯并呋喃和异香豆素衍生物的环化脱水合成方法。