CHIRAL COMPLEXES DESIGNED TO CATALYZE ORGANIC REACTIONS

这项提案中概述的研究项目的目标是 实用催化剂的设计、发现、开发和应用 选择性地产生光学活性形式的手性分子。 提高对绝对立体化学重要性的认识 药物功能提供了推动努力的主要动力 不对称催化剂。此外，基本的机械洞察力可能 来自高度立体选择性的过程。一个高度机械化的人 本研究项目采用催化剂设计方法，具有较高的实用价值 通过使用结合研究、动力学、结构功、 物理有机化学的模型体系和其他工具的研究 阐明和控制决定选择性的因素。 这项研究的广泛、长期目标包括：a) 评估催化剂设计的全新战略，b) 不对称有机反应催化剂的发现与发展 具有广泛的综合重要性，c)阐明了 本研究中发现的催化剂的反应，以及d) 通过这些催化剂的应用说明它们的用途 在合成生物上重要的靶标方面。 该项目的具体目标涉及到催化剂的各种方法 设计。最近开发的不对称环氧化催化剂是一种 获得高对映体选择性的基础 烷基取代烯烃和单取代烯烃的氧化。 生物氧化催化剂的评价与发展 还进行了氯过氧化物酶活性测定。新的催化策略也在 为实现对映体选择性转化而提出的 现在可以通过(Salen)Mn-和氯过氧化物酶-获得丰富的环氧化物- 催化环氧化反应。 新近发现的用于不对称氮杂环化反应的催化剂 非常简单且可人工合成的双亚胺配体。 基于这些配体的机械和合成策略 介绍了正在开发的实用的氮杂环化催化剂。 联西亚胺配体也将作为配体在其他合成中被评估 重要的不对称反应，如手性路易斯酸催化 流程。 在提案的最后一部分，一项新的设计和 在鲍林模型的基础上，提出了开发不对称催化剂的设想 用于酶催化。

The goal of the research projects outlined in this proposal is the design, discovery, development, and application of practical catalysts that selectively generate chiral molecules in optically active form. Increasing awareness of the importance of absolute stereochemistry in drug function provides the major driving force behind efforts in asymmetric catalysts. In addition, fundamental mechanistic insights may be derived from highly stereoselective processes. A highly mechanistic approach to catalyst design is adopted in this research program, with application of through use of binding studies, kinetics, structural work, the study of model systems, and other tools of physical organic chemistry to elucidate and control the factors that determine selectivity. The broad, long-term objectives of this research include: a) the evaluation of fundamentally new strategies for catalyst design, b) the discovery and development of catalysts for asymmetric organic reaction of broad synthetic importance, c) the elucidation of the mechanism of reaction of the catalysts that are discovered in this research, and d) illustration of the utility of these catalysts through their application in the synthesis of biologically important targets. The specific aims of this project involve various approaches to catalyst design. Recently developed asymmetric epoxidation catalysts serve as a basis for directed toward attainment of high enantioselectivity in the oxidation of alkyl-substituted alkenes and mono-substituted olefins. Evaluation and development of biological oxidation catalysts such as chloroperoxidase is also undertaken. New catalytic strategies are also presented for accomplishing selective transformation of enantiomerically enriched epoxides now accessible via(salen)Mn-and chloroperoxidase- catalyzed epoxidation. Recently-discovered catalysts for enantioselective aziridination employ remarkably simple and synthetically accessible bisimine ligands. Mechanistic and synthetic strategies based on these ligands for developing aziridination catalysts of practical utility are presented. Bisimine ligands will also be evaluated as ligands in other synthetically important asymmetric reactions, such as chiral Lewis acid catalyzed processes. In a final section of the proposal, a new strategy for designing and developing asymmetric catalysts is advanced, based on the Pauling model for enzymatic catalysis.