CHIRAL COMPLEXES DESIGNED TO CATALYZE ORGANIC REACTIONS

旨在催化有机反应的手性配合物

• 批准号: 2181880
• 负责人: ERIC N JACOBSEN
• 金额: $ 22.96万
• 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/2181880
• 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 其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在化学中的重要性的认识 药物功能提供了努力的主要驱动力， 不对称催化剂 此外，基本的机械见解可能 可以从高度立体选择性的过程中获得。 一种高度机械化的 本研究采用催化剂设计方法， 通过使用结合研究、动力学、结构工作， 研究模型系统和其他物理有机化学工具 阐明和控制决定选择性的因素。 这项研究的广泛和长期目标包括：a） 评价催化剂设计的基本新策略，B） 不对称有机反应催化剂的发现与发展 具有广泛的合成重要性，c）阐明了 本研究中发现的催化剂的反应，以及d） 通过它们的应用说明这些催化剂的效用 合成生物学上重要的目标。 该项目的具体目标涉及催化剂的各种方法 设计 最近开发的不对称环氧化催化剂用作 的基础，直接实现高对映体选择性， 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， 也进行氯过氧化物酶。 新的催化策略也 提出用于实现对映体的选择性转化 富集的环氧化物现在可以通过（salen）Mn-和氯过氧化物酶- 催化的环氧化反应。 最近发现的用于对映选择性氮杂环丙烷化的催化剂采用 非常简单且可合成的双亚胺配体。 基于这些配体的机制和合成策略， 介绍了开发具有实用价值的氮杂环丙烷化催化剂。 双亚胺配体也将作为配体在其他合成中进行评价。 重要的不对称反应，如手性刘易斯酸催化的 流程. 在提案的最后一部分，提出了一项新的设计和 在Pauling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。