二烯化合物的区域及对映选择性胺基化反应研究

Regio- and enantioselective control of the multi-active-site substrates has always been a hot and challenge topic in organic synthesis. Dienyl allylic alcohol/ester is a typical multi-reactive site substrate with three reactive sites C1, C3 and C5. The traditional Tsuji-Trost type reaction can achieve excellent regio- and stereoselective control at C1 and C3 sites. While the high selective substitution at C5 site is the difficulty of this kind of reaction, to the best of our knowledge, the C5-amination has not been reported in the literature before. Few studies on the C5 selective substitution has limited the development and application of the dienyl substrates. Therefore, this project intends to develop a new method for regio- and stereoselective amination at C5 of the dienyl compounds in transition-metal-catalyzed condition. The intra- and inter-molecular regio- and stereoselective amination at C5 site can be achieved by means of substrate design and catalytic system screening. What’s more, by analyzing the experimental results and exploring the mechanism, we can further understand the reaction differences between C1, C3 and C5 sites, and provide experimental and theoretical basis for the better development of C5 hybrid substitution. At the same time, we extend the substrates to conjugated polyene allylic alcohol/ester to achieve C(2n+3) selective amination.

多反应位点化合物的区域及对映选择性控制一直是有机合成的热点和难点。二烯基烯丙基醇/酯是一类典型的多反应位点化合物，具有C1,C3和C5三个反应位点，传统的Tsuji-Trost反应类型能实现C1和C3位优秀的区域及立体选择性控制，而C5位高选择性取代是该类反应的难点，且C5位区域选择性胺基化目前未有相关文献报道。有限的C5位选择性反应研究制约了二烯基底物的发展和应用。因此，本项目拟开展二烯基底物C5位区域及对映选择性胺基化反应研究，通过底物设计、催化体系筛选等手段，实现二烯基底物分子内和分子间C5位区域及立体选择性胺基化。通过对实验结果分析及机理探索，进一步了解该类化合物C1,C3和C5位点之间的反应差异性，为更好地发展C5位杂原子取代提供实验基础和理论依据。同时，我们将底物延伸到共轭多烯基烯丙基醇/酯，以期实现C(2n+3)位点选择性胺基化。

多反应位点化合物的区域及对映选择性控制一直是有机合成的热点和难点。1,4-二烯基-3-醇化合物是一类典型的多反应位点化合物，具有C1/C3和C5三个反应位点。本项目开展了二烯基底物区域及对映选择性胺基化反应研究，通过底物设计、催化体系筛选等手段，实现二烯底物分子内和分子间C1/C3/C5位区域选择性胺基化以及C3/C5的立体选择性胺基化。通过对实验结果分析及机理探索，进一步了解该类化合物C1、C3和C5位点之间的反应差异性，为更好的发展C1/C3/C5位杂原子取代提供实验基础和理论依据。在该经费资助下，目前已发表论文3篇