Asymmetric Ruthenium Catalyzed Coupling of Alkynes and Primary Alcohols Towards syn-Crotylation Products

炔烃和伯醇的不对称钌催化偶联生成顺巴豆酰化产物

• 批准号: 320911414
• 负责人: Dr. Matthias Bender
• 金额: --
• 依托单位: Department of Chemistry
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/320911414?language=en
• 关键词: Asymmetric; Ruthenium; Catalyzed; Coupling; Alkynes

The direct functionalization of carbon-hydrogen bonds in combination with carbon-carbon bond formation owns the future in modern organic chemistry. Catalytic systems which are able to activate the strong C-H bond in a selective way operate in high synthetic efficiency like atom- and step-economy and enable greener chemistry pathways. The group of Prof. M. J. Kirsche develop ruthenium based catalytic systems allowing a mild and direct C-H functionalization of primary alcohols by C-C bond coupling with pi-unsaturated reactants in high chemo-, diastereo- and enantioselectivity. By this method important acetate and propionate based building blocks are obtained for construction of polyketides. These are natural products with great importance in application for human medicine. As mostly all commercial available polyketide drugs are derived by fermentation processes the hydro-hydroxyalkylation method enables an efficient and new strategy towards these important natural products as classical chemical methods are not competitive. Recently the bandwidth of pi-unsaturated reactants applied for coupling with primary alcohols was extended to the use of alkynes forming products of formal carbonyl crotylation in high anti-diastereoselectivity. With this research a ruthenium catalyzed alkyne mediated syn-diastereo- and enantioselective redox-triggered alcohol C-H crotylation will be developed. As a key transformation a novel ruthenium(0)-derived 1,2-silyl shift of alpha-silyl-alkynes will be explored forming defined silyl-substituted allyl complexes that are expected to react in a high selective way. On this way the alkyne derived pool of important syn-crotylation building blocks for polyketide construction will be extended.

碳氢键的直接官能化与碳碳键的形成是现代有机化学的发展方向。能够选择性激活强碳氢键的催化系统以原子经济和阶梯经济等高合成效率运作，并实现更环保的化学途径。M. J. Kirsche教授的研究小组开发了基于钌的催化体系，通过C-C键与非饱和反应物偶联，在高化学、非映对和对映选择性下，使伯醇具有温和和直接的C-H官能化。通过这种方法，获得了重要的醋酸酯和丙酸酯基构建块，用于构建聚酮。这些天然产物在人类医学应用中具有重要意义。由于大多数商业上可用的聚酮类药物都是通过发酵过程衍生的，因此氢化羟基烷基化方法为这些重要的天然产物提供了一种有效的新策略，而传统的化学方法没有竞争力。近年来，应用于伯醇偶联的pi-不饱和反应物的带宽已扩展到使用炔形成具有高抗非对映选择性的正羰基丁基化产物。本研究将开发钌催化炔介导的顺非映对和对映选择性氧化还原醇C-H丁基化反应。作为一个关键的转变，一个新的钌(0)衍生的1,2-硅基转移的α -硅基炔将被探索形成明确的硅基取代的烯丙基配合物，预计将以高选择性的方式反应。通过这种方式，用于聚酮构建的重要的同丁基化构建块的炔衍生池将得到扩展。