手性有机小分子催化八面体金属配合物的不对称合成研究

General methods for the stereocontrolled synthesis of octahedral metal complexes areurgently needed in order to fully exploit the structural opportunities offered by octahedral coordination spheres in the areas of materials sciences and the life sciences. For example, octahedral metal complexes play an increasingly important role as structural scaffolds for the design of nucleic acid probes and enzyme inhibitors and for such applications of molecular recognition typically single enantiomers are desired. .A few years ago we therefore started a research program that focuses on the development of chiral auxiliaries. We now aim to go an important step further and propose to develop organic catalysts for asymmetric coordination chemistry. The proposal has the long-term objective to initiate and establish a new area of research by developing general methods for the efficient and economical catalytic asymmetric synthesis of substitutionally and configurationally inert octahedral chiral-at-metal coordination compounds..Specifically, we aim to investigate three distinguished catalytic strategies: In a first strategy, based on successful initial results, asymmetric catalysis includes as a key step an asymmetric trans-cis isomerization. In a second strategy, anchimeric assistance will be exploited to design catalysts in which the activation and following disintegration of half-sandwich complexes will be initiated by the attack of a strongly nucleophilic anchimeric ligand. In a third strategy, asymmetric catalysis through an induced oxidative decarbonylation will be pursued. Successfully developed catalytic methods will then be applied to the asymmetric synthesis of more complicated and bioactive metal complexes.

为了深入研究八面体过渡金属配合物在材料科学及生命科学中的应用，发展通用有效的立体选择性合成方法迫在眉睫。在此，我们通过设计与合成新型的手性有机小分子催化剂，系统发展经济高效的不对称催化方法合成结构和构型稳定的手性金属八面体配合物，同时探索手性有机小分子在立体选择性合成中的催化机理，为催化剂的设计和优化提供依据。具体内容包括：设计与合成具有新型结构的手性亚砜、手性联萘等类催化剂，用于研究：1）涉及反式-顺式异构化的不对称催化；2）涉及邻位协同效应的不对称催化；3）涉及氧化脱羰基过程的不对称催化；4）不对称催化在复杂生物活性体系中的应用。.这项工作将开辟不对称催化合成的新领域，进一步丰富催化学科所涵盖的研究内容，同时为手性八面体配合物的应用奠定坚实的物质基础、大幅度促进各项研究的进程，是一项具有长远意义的国际前沿性研究课题。

本项目的目标是发展经济高效的不对称合成及催化方法，用于制备结构和构型稳定的手性金属八面体配合物，同时探索八面体手性配合物的应用进行初步探索。项目的执行情况良好，完成或超过既定目标，包括：在合成方法学上，已发展多种手性小分子配体，应用于八面体手性钌、锇、铱、铑配合物的合成中，原料易得，步骤简便，所获产物均具有较高的光学纯度，成为获取该类特殊手性化合物最为高效的方法；在性能上，发现八面体手性配合物产物是构建高效不对称催化剂的良好骨架，通过对铱、铑八面体手性配合物结构的精密修饰，获得了一系列多功能氢键、Brønsted碱、Lewis酸催化剂，在多种有机不对称反应表现出极高的效率。在八面体手性配合物的自身催化合成中，虽然所设计有机配体表现出一定的催化效率，但对于立体选择性的控制却并不理想。我们通过一系列控制实验、分步研究、理论计算，详细探讨原因，为今后工作的开展提供理论和实验依据。