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

碳-氢键的直接功能化与碳-碳键的形成相结合是现代有机化学的发展方向。能够以选择性方式激活强C-H键的催化体系以高合成效率（如原子和步骤经济性）运行，并实现更绿色的化学途径。M. J. Kirsche开发了基于钌的催化体系，其允许伯醇通过C-C键与π-不饱和反应物偶联以高化学选择性、非对映选择性和对映选择性进行温和和直接的C-H官能化。通过这种方法，获得了用于构建聚酮化合物的重要的基于乙酸酯和丙酸酯的结构单元。这些是在人类医学应用中具有重要意义的天然产物。由于大多数市售的聚酮药物都是通过发酵工艺获得的，因此加氢-羟烷基化方法能够实现对这些重要天然产物的有效和新的策略，因为经典的化学方法没有竞争力。最近，用于与伯醇偶联的π-不饱和反应物的带宽被扩展到以高反非对映选择性使用形成形式羰基巴豆酰化产物的炔。本研究将发展钌催化炔介导的顺式-非对映-和对映选择性氧化还原引发的醇C-H巴豆酰化反应。作为一个关键的转变，一种新的钌（0）衍生的α-甲硅烷基-炔的1，2-甲硅烷基位移将被探索形成定义的甲硅烷基取代的烯丙基配合物，预计以高选择性的方式反应。通过这种方式，用于聚酮化合物构建的重要的顺丁烯基化结构单元的炔衍生池将被扩展。

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.