电化学促进的不对称构筑联芳基轴手性化合物的研究

Biaryls have been widely used in chiral ligands, organic chiral catalysts, natural products and drug-active molecules. Many methods, such as metal catalysis or organic catalysis, have been applied to the asymmetric construction of chiral biaryls. However, there are still some shortcomings in these methods: a) the need for stoichiometric chiral auxiliaries; b) the need for stoichiometric oxidants or reductants; c) the need for pre-functionalization of reaction substrates; d) the inefficiency of asymmetric induction; and so on. In this project, two strategies, asymmetric hydrocarbon bond functionalization catalyzed by transition metals under electro-oxidation conditions or asymmetric reduction coupling catalyzed by transition metals under electro-reduction conditions, would be used to construct optically active axially chiral compounds. In this project, new redox mediator and catalysts would be developed by studying the compatibility of metal catalysts, chiral ligands, electrolytes and redox mediator. Under electrochemical conditions, the asymmetric construction of biaryl chiral compounds catalyzed by metal with high efficiency can not only avoid the use of oxidants or reductants in traditional thermochemistry, but also achieve chemical conversion that is difficult to achieve in thermochemistry, and provide a alternative way for the synthesis of biaryl chiral compounds.

联芳基类的轴手性骨架广泛存在于手性配体、有机手性催化剂、天然产物以及具有药物活性的分子中。金属催化或者有机催化等多种方法均已应用到了手性联芳基类化合物的不对称构筑中。然而这些方法中仍然存在一些缺点：a）需要化学计量的手性辅基； b）需要化学计量的氧化剂或者还原剂；c）反应底物需要预先官能团化； d）不对称诱导的效率不高等。本研究项目通过在电氧化学条件下实现过渡金属催化的不对称碳氢键官能团化反应，或者在电还原条件下实现过渡金属催化的不对称还原偶联反应两种策略来高效构筑具有光学活性的轴手性化合物。拟通过对金属催化剂、手性配体、电解质、媒介的兼容性等系统的研究，开发出新型的媒介以及催化剂。在电化学条件下实现高效的金属催化的不对称构筑联芳基类手性化合物的方法不仅可以避免传统热化学中氧化剂或者还原剂的使用而且可以实现热化学中难以实现的化学转化，为联芳基类手性化合物的合成提供一条新型的途径。

联芳基类的轴手性骨架广泛存在于手性配体、有机手性催化剂、天然产物以及具有药物活性的分子中。金属催化或者有机催化等多种方法均已应用到了手性联芳基类化合物的不对称构筑中。然而这些方法中仍然存在一些缺点：a）需要化学计量的手性辅基；b）需要化学计量的氧化剂或者还原剂 ；c）反应底物需要预先官能团化；d）不对称诱导的效率不高等。在电化学条件下，在过渡金属铜，铑，镍，以及有机小分子等催化剂作用下，本项目实现了各类电化学转化反应：对映选择性炔基化反应，选择性溴化反应，环化反应，对映选择性氧化偶联反应，对映选择性电化学还原偶联反应，胺化反应等。该项目不仅可以高对映选择性地合成轴手性化合物，还可以构筑一系列具有合成应用价值的有机小分子。