3d过渡金属催化的不对称自身氢转移反应研究

Asymmetric self-hydride transfer reaction has burgeoned in the field of asymmetric hydrogenation, as this approach offers elevated atom efficiency, environmental benefits and no requirement of additional reducing agents. Currently, it relies on using heavy metal catalysts. However, several issues of these catalysts such as high costs, toxicity, and poor sustainability of processes cause evitable limitations on practicity. This project aims to develop high enantioselective and catalytic earth-abundant 3d-metal catalytic systems for asymmetric self-hydride transfer reactions. New families of chiral bis(alkylphosphine)s will be created by using an inexpensive chiral pool to make a large library of 3d-metal catalysts. Allylic alcohols with different directing groups will be designed and synthesized for 3d-metal-catalyzed enantioselective isomerization of allylic alcohols. The alkylation of amines by the respective alcohols through asymmetric borrowing hydrogen catalysis will be investigated by this novel catalytic system. These developed new catalysts will be also applied for the synthesis of high-value chiral amine intermediates. On the basis of experimental results and theoretical calculation, further mechanism study will be carried out. This project will indefinably widen the current synthetic perspective of asymmetric catalysis by developing new synthetic routes. It also offers a low-cost, effective and convenient approach for the synthesis of high-value chiral drugs in the pharmaceutical industry.

不对称自身氢转移反应由于其原子经济性高，环境友好，且无需额外的还原剂，已成为不对称氢化研究领域的新热点。但该反应使用的催化剂主要是贵金属，它们不仅价格贵，毒性大，且存有量低。本项目拟通过廉价的3d过渡金属催化体系，高选择性地实现不对称自身氢转移反应。首先，利用廉价的手性化合物骨架，设计与制备具有潜在高活性的手性双膦配体，丰富3d过渡金属催化体系的类型。其次，通过烯丙醇衍生物导向基团的优化设计与制备，高效地实现3d过渡金属催化的烯丙醇衍生物的不对称异构化反应。同时，通过反应体系的进一步优化，高效地实现醇与胺不对称“借氢”反应和含有手性胺骨架的药物分子中间体的合成。最后，基于实验与理论计算的结果，深入研究3d过渡金属催化的不对称自身氢转移反应的反应机理。本项目的实施将为手性化合物的合成开辟新的合成路线，扩大目前不对称合成的应用前景。同时，为药物创新合成提供低成本且简洁高效的合成路线。

不对称自身氢转移反应由于其原子经济性高，环境友好，且无需额外的还原剂，已成为不对称氢化研究领域的新热点。但该反应使用的催化剂主要是贵金属，它们不仅价格贵，毒性大，且存有量低。本项目拟通过廉价的3d过渡金属催化体系，高选择性地实现不对称自身氢转移反应。首先，利用廉价的手性化合物骨架，设计与制备具有潜在高活性的手性双膦配体，丰富3d过渡金属催化体系的类型。其次，通过烯丙醇衍生物导向基团的优化设计与制备，高效地实现3d过渡金属催化的烯丙醇衍生物的不对称异构化反应。同时，通过反应体系的进一步优化，高效地实现醇与胺不对称“借氢”反应和含有手性胺骨架的药物分子中间体的合成。最后，基于实验与理论计算的结果，深入研究3d过渡金属催化的不对称自身氢转移反应的反应机理。本项目的实施将为手性化合物的合成开辟新的合成路线，扩大目前不对称合成的应用前景。同时，为药物创新合成提供低成本且简洁高效的合成路线。