CHIRAL COMPLEXES DESIGNED TO CATALYZE ORGANIC REACTIONS

旨在催化有机反应的手性配合物

• 批准号: 2181881
• 负责人: ERIC N JACOBSEN
• 金额: $ 25.26万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2181881
• 关键词: alkenes; catalyst; chemical synthesis; cyclization; epoxides; method development; peroxidases; stereochemistry

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.

本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。 提高人们对绝对立体化学重要性的认识 药物功能是努力的主要推动力 不对称催化剂。 此外，基本的机制见解可能 源自高度立体选择性过程。 高度机械化 本研究计划采用催化剂设计方法， 通过结合研究、动力学、结构工作的应用， 模型系统和其他物理有机化学工具的研究 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： 评估催化剂设计的全新策略，b) 不对称有机反应催化剂的发现和开发 具有广泛的综合重要性，c）阐明其机制 本研究中发现的催化剂的反应，以及 d) 通过应用说明这些催化剂的效用 在生物学上重要的靶标的合成中。 该项目的具体目标涉及各种催化剂方法 设计。 最近开发的不对称环氧化催化剂 为实现高对映选择性奠定了基础 烷基取代的烯烃和单取代的烯烃的氧化。 生物氧化催化剂的评价和开发，例如 还进行了氯过氧化物酶检测。 新的催化策略也 提出用于完成对映体的选择性转化 现在可以通过(salen)Mn-和氯过氧化物酶-获得富集的环氧化物 催化环氧化。 最近发现的用于对映选择性氮丙啶化的催化剂 非常简单且易于合成的双亚胺配体。 基于这些配体的机理和合成策略 介绍了正在开发的实用的氮丙啶化催化剂。 双亚胺配体也将作为其他合成中的配体进行评估 重要的不对称反应，例如手性路易斯酸催化 流程。 在提案的最后一部分，提出了一个新的设计和 基于鲍林模型，开发不对称催化剂已取得进展 用于酶催化。