新型手性双齿硼基配体的合成及其在不对称碳氢键硼化反应中的应用研究

Design and synthesis of novel chiral ligands is an eternal theme of asymmetric catalysis. It is not only the need to improve the efficiency and selectivity of current catalytic systems, but also the inevitable requirement for achieving new reactions and complementary selectivity and creating new chiral molecules. According to the development trend and the latest principles of chiral science, the project will focus on design and synthesis of novel chiral bidentate boryl ligands with boron as the supporting atom to expand the scope of chiral ligands. The new ligands will be applied to the iridium-catalyzed C-H borylation reactions, including desymmetrization of prochiral substrates and methylene C(sp3)-H borylation to expediting the construction of single enantiomer in a precise manner. At the same time, it will also provide atom- and step- economic methods to the rapid synthesis of bioactive compounds. In addition, the mechanistic investigations, including computational studies will also be conducted, which will provide the clue of the chiral induction of such ligands by analyzing the relationship between reaction properties (eg, reactivity and stereoselectivity) and the nature of the ligand (eg, the scaffold of the ligand, the position, the size, and electronic properties of the substituent. By summarizing general rules of the ligand performance, the project will give a certain scientific guidance to develop other types of chiral boryl ligands, promoting the development of chiral science.

新型手性配体的设计与合成是不对称催化中永恒的主题，它不仅是提高现有催化体系效率与选择性的需要，同时也是实现新反应、新选择性和创制新的手性分子的必然要求。本项目根据手性科学的发展要求和最新原理，突破手性配体传统配位原子局限于碳、氮、氧、硫和磷的限制，设计与合成以硼作为配位原子的新型手性双齿硼基配体，拓展手性配体的范畴，并系统研究它们的铱络合物在去对称化碳氢键硼化和亚甲基的对映选择性碳氢键硼化反应中的应用，实现单一镜像异构体的快速精准构筑，同时希望为生物活性分子的快速合成方法提供原子和步骤经济的方法。此外，本项目拟通过研究反应机理，探讨配体骨架、取代基位置、大小和电性同反应活性和立体选择性之间的关系，并结合理论计算，揭示该类型配体的不对称诱导机制，总结一般规律，为发展其它类型的手性硼基配体提供一定的科学依据，推动手性科学的发展。

新型手性配体的设计与合成是不对称催化中永恒的主题，它不仅是提高现有催化体系效率与选择性的需要，同时也是实现新反应、新选择性和创制新的手性分子的必然要求。本项目根据手性科学的发展要求和最新原理，围绕新型手性双齿硼基配体的设计与合成开展研究工作，具体来说，主要包含以下部分：1）设计与合成了超过40个结构多样的新型手性双齿硼基配体；2）通过手性双齿硼基配体/铱催化的亚甲基的对映选择性碳氢键硼化反应，实现了α-手性环状胺、β-手性酰胺和β-手性吡唑类化合物的高效、高对映选择性合成；3）通过手性双齿硼基配体/铱催化的去对称化碳氢键硼化反应，实现了手性张力环、磷中心手性、硫中心手性、平面手性和轴手性的高效、高对映选择性构建；4）利用碳氢键硼化产物，实现了若干手性生物活性分子的不对称合成；5）结合单晶、非线性效应、原位核磁和计算化学，进行了机理研究。本项目共发表学术论文10篇，其中 J. Am. Chem. Soc. (1篇)，Angew. Chem. Int. Ed. (5篇), ACS Catal. (2篇)， Chin. J. Chem.(1篇)，Asian J. Org. Chem.(1篇)。