氧气介导的非活化烯烃碳碳双键断裂转化反应及其在合成中的应用

Carbon-carbon double bond is one of the most common bonds in organic compounds. Although the research on carbon-carbon double bond cleavage has been conducted for decades, challenges remain in many aspects. The traditional methods of carbon-carbon double bond cleavage are mainly focus on the olefin metathesis reactions, and the ozone or strong oxidant catalyzed carbon-carbon double bond decomposition reactions. Considerable effort has been devoted to the molecular oxygen mediated cleavage of alkenes. However, in previous reports, the oxygen-mediated carbon-carbon double bond cleavage substrate scope, which is often restricted to simple styrene or high tension cycloolefin, the need for pressures higher than atmospheric, and relatively high catalyst ratios are still present in several reports on this issue. The cleavage of carbon-carbon double bonds in non-activated alkenes has rarely been reported. Therefore, it is still a great challenge to develop a mild and efficient method to use oxygen as oxidant to break the carbon-carbon double bond of non-activated alkenes. This project intends to develop an oxygen-mediated unactivated carbon-carbon double bond cleavage methods, and explore the rule of oxygen activation and its interaction with unactivated olefins and reaction mechanism, and provide new ideas for the application of oxygen activation in other organic reactions. A series of new compounds with potential drug activity were synthesized by this method, and their biological activities and pharmacokinetics will be studied.

碳碳双键是有机化合物中最常见的化学键之一。尽管对碳碳双键断裂的研究已经进行了几十年，但是该问题在许多方面仍然充满了挑战。传统碳碳双键断裂转化的方法主要为贵金属促进的烯烃复分解反应，或者使用臭氧或强氧化剂实现的对碳碳双键的分解反应。使用氧气作为氧化剂，实现对碳碳双键断裂的研究也取得了一定的进展，但是底物范围主要集中在苯乙烯或者高张力环内烯烃中，且反应往往需要高于大气压的压力和较高的催化剂比例，对于非活化烯烃的碳碳双键的断裂则鲜有报道。因此发展温和高效的方法，使用氧气作为氧化剂实现非活化烯烃碳碳双键的断裂仍然是一个很大的挑战。本项目拟发展氧气介导的非活化烯烃碳碳双键的断裂的方法，探索氧气活化的规律及其与非活化烯烃的相互作用和反应机理，为氧气活化在其他有机反应中的应用提供新思路。并且用该方法合成一系列具有潜在药物活性的新型化合物，并对新合成的一系列化合物进行生物活性和成药性方面的研究。

发展有机合成新反应一直是有机化学发展的核心部分之一，是推动有机化学不断创新不断进步的根本动力。碳碳双键、碳碳单键和碳氢键都是构成有机化合物最基础的化学键结构。所以发展碳碳双键、碳碳单键和碳氢键的断裂修饰新方法是有机化学最重要的研究课题之一。在该项目的研究过程中，我们尝试了一系列的方法，希望能够实现对碳碳双键、碳碳单键和碳氢键的氧化断裂修饰反应。最后我们发现，当使用具有氧化还原活性的胺化试剂作为胺源时，烷基芳烃或者苄醇类化合物能够发生选择性碳碳单键的断裂反应，从而实现一系列苯胺衍生物的制备。同时我们发现，当使用催化量的氧化钡作为催化剂、氘代水作为氘源，能够高效的实现酮、亚砜、砜和腈类化合物的α-氘代反应。以上两类反应都能在生物活性分子的后期修饰中得到广泛的应用。