CHIRAL COMPLEXES DESIGNED TO CATALYZE ORGANIC REACTIONS

本研究计划的目的是设计和研究可溶性 对映选择性催化合成的过渡金属络合物 有机化合物的有价值的转化。不对称催化剂可以 提供了最有效和最实用的途径， 光学纯材料，以及对映体纯材料的需求 需要用于宽范围底物的高度立体选择性催化剂。 本提案着重于手性药物的开发和研究 水杨醛缩亚氨基（salen）基环氧化催化剂。初步研究 已经揭示了基于Salen的系统提供了手性的实际途径， 来自非官能化烯烃的环氧化物， 选择性。将对映体选择性提高到非常高水平的策略 概述了基于提出的高度预测立体化学模型， 从金属到烯烃的氧原子转移。该模型将彻底 使用晶体学和溶液相表征测试， 催化剂前体和活性中间体。基质相关性 并且具有观察到的对映选择性的催化剂结构然后可以允许 的过渡结构几何形状的宝贵见解 氧原子从金属转移到烯烃。 手性salen配合物是非常容易通过简单的高产率 合成程序，这允许筛选各种潜在的 催化剂的描述了用于系统地调整空间位阻的策略。 Salen配体的性质，包括空间上的制备 受阻水杨醛衍生物的合成及多种新的 C2-对称手性二胺。催化剂寿命将通过以下方式最大化 配体和金属的变化，以及分解的鉴定 在严格控制的反应条件下进行。 现有的和新开发的催化剂的合成效用将 可以通过一系列未官能化和高度官能化的反应来说明。 复杂的基板，并通过执行大规模的不对称 从简单烯烃得到有价值的手性产物的环氧化反应。与 适当的发展，手性salen为基础的系统将提供以前 难以接近的手性结构单元和最终产品， 药物合成 现有的和新开发的salen基配合物的可能用途 作为不对称催化剂在其它反应中的应用也将被考察。针对性 应用包括氯醇环化、硫化物氧化和刘易斯 酸促进的烷基化和羰基化合物的环加成。

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.