Iron-Catalyzed Metathesis and Carbocation Cyclization Reactions

铁催化复分解和碳正离子环化反应

• 批准号: 9193824
• 负责人: Corinna Stefanie Schindler
• 金额: $ 31.73万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9193824
• 关键词: Alkaloids; Alkenes; Alkylation; Area; Benign; Biological; Carbon; Chemicals; Chemistry; Complex; Cyclization; Cyclopentenes; Development; Evaluation; Furans; Generations; Genomics; Health; Human; Indenes; Investigation; Iron; Ketones; Knowledge; Lead; Libraries; Medicine; Metals; Methodology; Methods; Michigan; Mission; Molecular; Naphthalenes; Natural Products; Pharmacologic Substance; Procedures; Protocols documentation; Public Health; Pyrans; Pyrroles; Reaction; Reagent; Research; Series; Source; Structure; System; Transition Elements; Universities; abstracting; analog; base; biological research; catalyst; cycloaddition; cyclohexene; drug discovery; functional group; high throughput screening; improved; insight; novel strategies; novel therapeutics; oxetane; pharmacophore; phenanthrene; programs; pyridine; scaffold; tool

Project Summary/Abstract The metathesis reaction between two alkenes represents a powerful tool for the formation of carbon-carbon bonds, which has led to profound synthetic applications in a large variety of biologically active target structures. The corresponding carbonyl-olefin metathesis reaction enables direct carbon-carbon bond construction, however, currently available synthetic methods are severely limited by harsh reaction conditions or require the use of stoichiometric metal alkylidene complexes as reagents. To date, no protocol of general synthetic utility for catalytic carbonyl-olefin metathesis exists. The objective of the proposed research program is to identify a chemical strategy that enables the catalytic carbonyl-olefin metathesis and related carbocyclization reactions based on inexpensive and earth-abundant transition metals. A distinctive feature of this new methodology is that it will provide a general and modular protocol for the synthesis of a large variety of cyclic motifs incorporated in many ubiquitous chemical scaffolds and biologically active complex molecules. Additionally, this new approach enables carbonyl-olefin metathesis reactions under mild reaction conditions with high functional group tolerance. In particular, highly functionalized carbocycles which all constitute core components of pharmacophores with a wide array of biological activities, will be directly accessible in a single transformation. Such carbocycles include cyclopentenes, cyclohexenes, furans, pyrans, pyridines and their analogs, indenes, napthalenes, spirocyclic, polycyclic as well as biaryl building blocks. The utility of these new carbocyclization reactions catalyzed by earth-abundant transition metals will be demonstrated by enabling the synthesis of biologically active target structures from simple, and readily available starting materials. The compounds prepared within this research program will be incorporated into the compound library maintained by the Center for Chemical Genomics (CCG) at the University of Michigan and become part of high-throughput screening (HTS) approaches for biological research and novel drug discovery projects. In summary, the research proposed will establish the first general, catalytic carbonyl-olefin metathesis reaction employing earth-abundant transition metals as a new tool for direct carbon-carbon bond construction which is expected to have wide implications for the area of complex molecule synthesis.

项目总结/摘要 两个烯烃之间的复分解反应代表了形成碳-碳的有力工具 键，这导致了广泛的合成应用在各种各样的生物活性的目标结构。 相应的羰基-烯烃复分解反应使得能够直接构建碳-碳键， 然而，目前可用的合成方法受到苛刻反应条件的严重限制，或者需要 使用化学计量的金属亚烷基络合物作为试剂。到目前为止，还没有通用的合成实用程序， 存在催化羰基-烯烃复分解反应。拟议研究计划的目的是确定一个 能够进行催化羰基-烯烃复分解和相关碳环化反应的化学策略 基于廉价且地球上丰富的过渡金属。 这种新方法的一个显著特征是，它将为 合成了大量的各种各样的环状基序纳入许多普遍存在的化学支架和生物 活性复杂分子。此外，这种新方法使得羰基-烯烃复分解反应能够在 反应条件温和，官能团耐受性高。特别地，高度官能化的碳环 它们都构成了具有广泛生物活性的药效团的核心组分， 在一次转换中直接访问。这样的碳环包括环戊烯、环己烯、呋喃， 吡喃、吡啶及其类似物、茚、萘、螺环、多环以及联芳基结构 个街区.利用地球上丰富的过渡金属催化这些新的碳环化反应将是 通过使生物活性靶结构的合成能够从简单且容易地 可用的起始材料。在这项研究计划中制备的化合物将被纳入 密歇根大学化学基因组学中心（CCG）维护的化合物库 并成为生物研究和新药开发的高通量筛选（HTS）方法的一部分 探索项目 总之，本研究将建立第一个通用的催化羰基-烯烃复分解反应 使用地球上丰富的过渡金属作为直接碳-碳键构建的新工具， 预计将对复杂分子合成领域产生广泛影响。