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.

项目摘要/摘要 两种烷烃之间的元理性反应代表形成碳碳的强大工具 键，导致在各种生物活性目标结构中实现了深刻的合成应用。 相应的羰基 - 烯曲链复合反应使直接的碳碳键结构， 但是，目前可用的合成方法受到严格的反应条件的严重限制，或者需要 使用化学计量金属烷基二络合物作为试剂。迄今为止，尚无一般合成实用程序的协议 对于催化羰基 - 烯烃的分解存在。拟议的研究计划的目的是确定 化学策略，可以实现催化羰基 - 烯烃的分解和相关的碳环化反应 基于廉价和土壤丰富的过渡金属。 这种新方法的一个独特特征是，它将为 许多无处不在的化学支架和生物学上的多种循环基序的合成 活性复合分子。此外，这种新方法可以使羰基 - 烯烃的分解反应下 高功能组耐受性的轻度反应条件。特别是高度功能化的碳循环 所有这些都构成了具有广泛生物活性的药理的核心成分，将是 直接在单个转换中访问。这样的碳环弹性包括环体，环己烯，弗兰斯， pyrans，pyridines及其类似物，indenes，餐巾，螺旋细胞，多环和二聚体建筑物 块。这些新的碳环囊化反应的实用性将是由土壤丰富的过渡金属催化的 通过从简单而轻松地合成生物活性靶标结构来证明 可用的起始材料。本研究计划中准备的化合物将纳入 密歇根大学化学基因组学中心（CCG）维护的化合物库 并成为生物学研究和新药的高通量筛查（HTS）方法的一部分 发现项目。 总而言之，提出的研究将建立第一个将一般的催化羰基 - 烯烃的分解反应 采用土壤丰富的过渡金属作为直接碳碳键结构的新工具 预计将对复杂分子合成区域具有广泛的影响。