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.

碳氢键与碳碳键形成的直接功能化拥有现代有机化学的未来。能够以选择性方式激活强C-H键的催化系统以高合成效率（如原子和步骤经济）运行，并启用更绿色的化学途径。 M. J. Kirsche教授开发了基于钌的催化系统，允许通过C-C键与高化学化学，非对映射和对映选择性的PI不饱和反应物偶联来对原代酒精进行轻度和直接的C-H官能化。通过这种方法，获得了重要的醋酸盐和丙酸酯的构件，用于建造聚酮化合物。这些是天然产品，在应用人类医学方面非常重要。由于大多数商业可用的聚酮药物都是通过发酵过程得出的，因此羟基烷基化方法可以为这些重要的天然产物提供有效而新的策略，因为经典化学方法没有竞争力。最近，用于与初级醇的偶联的PI不饱和反应物的带宽扩展到在高抗抑制性的炔烃中形成正式的羰基共依依性的产物。通过这项研究，将开发氟噻吨催化的炔烃介导的合成型和对映体氧化还原触发的酒精C-H Crotyration。作为钥匙转换，将探索一个新型的（0）衍生的Alpha-Silyl-Alkynes的1,2-甲硅烷基移位，形成定义的Silyl取代的Allyl配合物，这些烯丙基复合物有望以高选择性的方式做出反应。这样，将扩大炔烃衍生的重要同步构基化构建块的聚酮化合物结构的池。