3-amido烯丙基乙烯基醚的催化不对称Claisen重排及三尖杉碱不对称合成研究

在过去的一个世纪中，Claisen重排在构建C-C键方面显示了巨大的潜力。随着人们对不对称合成越来越重视，不对称Claisen重排得到了一定的发展，但其手性主要源自原料或由等当量甚至过量的手性催化剂产生。而催化不对称Claisen重排目前在国内外仍处于起步阶段，其最大的挑战在于手性催化体系的催化效果极大地依赖于底物的结构和官能团特征。因此，对于含有特定官能团烯丙基乙烯基醚的催化不对称Claisen重排，设计并筛选合适的手性催化体系是至关重要的。本课题以3-amido烯丙基乙烯基醚为Claisen重排前体，设计合成一系列此类衍生物，筛选过渡金属Cu、Pd、Ru等催化剂和手性配体，并详细考察反应的反应条件、反应机理和立体选择性，以期找到该类型催化不对称Claisen重排的规律，为手性叔胺官能团开辟合成新途径。在已完成工作的基础上，应用此重排为关键反应，实现抗癌药物三尖杉酯碱母核的不对称合成。

In a century since it was dicsovered, Claisen rearrangement has shown significant potential for the C-C bong formation. As a result, the growing emphasis on asymmetric transformations has inspired the development of enantioselective reation variants of this concerted rearrangement. These transformtions have been applied in a stereocontrolled manner using either chiral substrates or stoichiometric chiral catalysts. However, catalytic asymmetric Claisen rearrangement with high enatioselectivity continue to be relatively rare. A key challenge to address this issue is identification of catalyst systems that affect rearrangement of functionalized allyl vinyl ethers with high enantioselectivity, which relies heavily on the structure and functional groups of precursors. This research project will design and synthesize a series of allyl vinyl ethers containing an amido group at C-3 position. We will screen the optimal catalysts and chiral ligands for the catalytic asymmetric Claisen rearrangement of this type of vinyl ethers. The reaction conditions, mechanism and stereoselectivity will be investigated in detail so as to find the rearrangement rule of this catalytic version of asymmetric transformations. Consequently, this project will provide a new synthetic approach to chiral tertiary amines. Based on our previous work, we will employ this catalytic asymmetric Claisen rearrangement as a key transformation to achieve the enantioselective synthesis of cephalotaxine.