烯烃[2+2]环加成反应及其高效光敏剂和非金属催化剂设计的理论研究

Since the four-membered ring is the remarkable structural feature of many bioactive natural products and drug molecules, the development of [2+2] cycloadditions of olefins, which are low energy consumption, high yields and high regioselectivity and stereoselectivity, has fundamental significance. Rencently, the radical anion/cation [2+2] cycoadditions by visible light photocatalysis and the organocatalytic [2+2] cycloadditions, which show excellent regioselectivity and srereoselectivity under mild reaction condition, have attractted our attentions. Although there have been a series of experimental studies on these reactions, the origins of the regioselectivity and srereoselectivity are not clear. In this project, we will investigate the cycloaddition mechanism of these two kinds of cycloaddition rections and design efficient visible photoredox catalysts (referred to as photosensitizers in the following text) and organocatalyst by performing quantum chemical calculations. The research content includes the following aspects: exploring the effects of the substituents on the regioselectivity and stereoselectivity of the radical anion/cation cycloadditions; finding the relationship between the ligand structures of the photosensitizer and their light-absorption wavelength; calculating the redox potential of the ground state and exicited state of the photosensitizer; trying to design new efficient photosensitizer depending upon the above investigation; exploring the mechanism of the activation of the olefins by the organocatalyst and the contribution of the weak interaction between the organocatalyst and the reactants to the control of the the regioselectivity and stereoselectivity of the cycloaddition; designing new organocatalyst for [2+2] cycloadditions which could control the stereostructure of the four-membered ring on purpose. On the basis of all the above investigation results,we will explore the new strategy for the synthesis of the four-membered ring with special stereostructure existing in natural products. We believe that our theoretical studies on the cycloaddition strategy for the synthesis of cyclobutane derivatives can provide very useful information for experimentalists to synthesize the natural products.

四元环是许多天然产物和药物分子中的重要结构单元。开发低能耗、高产率并能够控制四元环立体结构的烯烃[2+2]环加成反应意义重大。本项目将用量子化学计算方法研究可见光氧化还原催化剂（简称光敏剂）引发的离子自由基[2+2]环加成反应和非金属催化的[2+2]环加成反应，并对光敏剂和非金属催化剂进行理论设计。具体内容为：取代基性质对离子自由基环加成反应的反应活性、区域和立体选择性的影响；Ru、Ir等过渡金属配合物的配体结构与其吸收波长、基态和激发态的氧化还原性之间的关系，设计新型高效光敏剂；非金属催化剂活化烯烃[2+2]环加成反应的机理；非金属催化剂和反应物中取代基性质对反应的区域选择性和立体选择性的影响，设计能定向控制四元环结构的非金属催化剂；结合上述两类反应，设计合成与天然产物立体结构相对应的环丁烷衍生物的方法。本项目的研究可为实验上设计天然产物的合成过程提供新的思路和方法，具有潜在的应用价值。

四元环是许多天然产物和药物分子中的重要结构单元，开发低能耗、高产率、高选择性的烯烃[2+2]环加成反应，对于四元环的构建具有十分重要的意义。本项目采用量子化学计算方法研究了可见光引发的阴/阳离子自由基[2+2]环加成反应和三重激发态位能面上的[2+2]反应，以及非金属催化的[2+2]环加成反应，并对光敏剂和非金属催化剂进行了理性设计。我们从理论上验证了光敏剂不仅能通过电子转移引发烯烃的[2+2]反应，还可以通过能量传递的方式引发反应；发现了光敏剂的作用机理会因反应物的不同而发生改变，同一光敏剂对不同构型反应物的引发方式也存在差异。我们对光敏剂通过电子转移引发的阴/阳离子自由基[2+2]环加成反应进行了研究。烯酮分子间的[2+2]环加成反应发生在阴离子自由基和中性反应物之间；苯基乙烯基砜和烯酮分子间阴离子自由基[2+2]环加成反应包括自身环加成和交叉环加成两种形式；3,4-二氢吡喃与苯环上具有不同取代基的烯烃分子进行阳离子自由基[2+2]环加成反应。反应的区域及立体选择性因烯烃结构的不同可能由取代基的电子性质、空间位阻效应、p-p或p-π共轭效应中的某个或几个因素控制。我们对过渡金属络合物的性质进行了研究并设计了新的过渡金属络合物光敏剂，结果显示中心金属和配体结构对过渡金属络合物的吸收光谱、三重激发态与单重基态的能量差值ET以及氧化还原性能均有影响，新设计的可见光Pt配合物光敏剂不仅在可见光区有良好的吸收，而且具有较高的ET值（大于50 kcal/mol），预示其可以引发更多的反应。我们研究了非金属胺类催化的不饱和醛与烯烃分子间的[2+2]环加成反应。胺催化剂首先与不饱和醛形成烯胺中间体，实现对γ-位的活化作用，从而使[2+2]环加成反应能够在温和条件下发生。催化剂与反应物之间的氢键作用以及催化剂上取代基的空间位阻效应对区域选择性具有重要作用。此外，我们还研究了镍催化的共轭烯炔和烯烃分子间[2+2]环加成反应，阐明了导致该反应具有区域和立体选择性的内在本质。