CHIRAL COMPLEXES DESIGNED TO CATALYZE ORGANIC REACTIONS

本研究项目的目的是设计和研究可溶的 对映体选择性催化合成的过渡金属络合物 有价值的有机化合物转化。不对称催化剂可以 提供最有效、最实用的生物活性途径 光学纯材料，以及对映体纯材料的需求 要求为广泛的底物提供高度立体选择性的催化剂。 本方案的重点是手性化合物的开发和研究。 水杨醛缩氨基(Salen)环氧化催化剂。初步研究 揭示了基于Salen的系统提供了实际的手性途径 非官能化烯烃的环氧化物，具有很好到中等的性能 选择性。将对映体选择性提高到很高水平的策略 基于提出的高度可预测的立体化学模型 氧原子从金属转移到烯烃。模型将被彻底地 使用结晶学和溶液相表征进行测试 催化剂前体和活性中间体。底物相关性 而具有观察到的对映体选择性的催化剂结构则可以 对过渡结构几何的有价值的见解 氧原子从金属到烯烃的转移。 手性Salen络合物通过简单的高产率非常容易获得 合成程序，这允许筛选各种潜在的 催化剂。描述了系统地调整空间构型的策略 Salen配体的性质，包括立体结构的制备 受阻水杨醛衍生物及多种新化合物的合成 C2对称的手性二胺。催化剂寿命将通过以下方式最大化 配体和金属的变化及其分解的鉴定 在严格控制的反应条件下的路径。 现有的和新开发的催化剂的综合用途将 通过一系列非功能化和高度功能化的反应来说明 复杂的衬底，并通过大规模的不对称执行 从简单的烯烃得到有价值的手性产品的环氧化反应。使用 适当的开发，基于手性Salen的系统将以前提供 难以获得的手性构建块和最终产品，对 药物合成。 现有和新开发的Salen基络合物的可能用途 作为不对称催化剂在其他反应中也将被考察。目标明确 应用包括氯醇环化、硫化物氧化和刘易斯 酸促进的羰基化合物的烷基化和环加成反应。

The aim of this research program is the design and study of soluble transition metal complexes that enantioselectively catalyze synthetically valuable transformations of organic compounds. Asymmetric catalysts can provide the most efficient and practical routes to biologically active optically pure materials, and the need for enantiomerically pure materials calls for highly stereoselective catalysts for a broad range of substrates. This proposal focuses on the development and study of chiral salicylidenaminato (salen)-based epoxidation catalysts. Initial studies have revealed that salen-based systems provide practical access to chiral epoxides from a unfunctionalized olefins with very good to moderate selectivity. Strategies to increase enantioselectivity to very high levels are outlined based on a proposed highly predictive stereochemical model for oxygen atom transfer from metals to olefins. The model will be thoroughly tested using crystallographic and solution phase characterization of catalyst precursors and reactive intermediates. Correlation of substrate and catalyst structure with observed enantioselectivities can then permit valuable insight into the transition structure geometries of oxygen-atom-transfer from metal to olefin. The chiral salen complexes are very accessible through simple high-yield synthetic procedures, and this allows screening of a variety of potential catalysts. Strategies are described for systematic tuning of the steric properties of the salen ligands, including the preparation of sterically hindered salicylaldehyde derivatives and the synthesis of a variety of new C2-symmetric chiral diamines. Catalyst lifetimes will be maximized through variation of ligand and metal, and identification of the decomposition pathways under carefully controlled reaction conditions. The synthetic utility of the existing and newly developed catalysts will be illustrated through reactions on a series of unfunctionalized and highly complex substrates, and through the execution of large scale asymmetric epoxidations that afford valuable chiral products from simple olefins. With proper development, chiral salen based systems will provide previously inaccessible chiral building blocks and end-products of great value to pharmaceutical synthesis. The possible utility of existing and newly developed salen based complexes as asymmetric catalysts in other reactions will also be examined. Targeted applications include chlorohydrin cyclization, sulfide oxidation, and Lewis acid-promoted alkylations and cycloadditions of carbonyl compounds.