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

碳氢键的直接官能化与碳碳键的形成相结合是现代有机化学的发展方向。能够选择性地激活强C-H键的催化系统以原子和步骤经济的方式运行在高合成效率下，并使化学途径更加绿色。M.J.Kirsche教授的团队开发了基于Ru的催化系统，允许伯醇通过C-C键与高化学选择性、非对映选择性和对映选择性的pi-不饱和反应物进行温和和直接的C-H官能化。用这种方法可以得到用于构建聚酮的重要的醋酸基和丙酸基的构筑块。这些都是天然产物，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获得的，因此在经典化学方法不具竞争力的情况下，氢羟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。最近，用于与伯醇偶联的pi-不饱和反应物的带宽被扩展到用于生成具有高反非对映选择性的甲酰化反应产物的炔烃。通过这项研究，我们将开发一种Ru催化的炔烃催化的非对映对映和对映体选择性的氧化还原引发的醇的C-H巴曲化反应。作为一个关键的转变，我们将探索一种新的Ru(0)衍生的1，2-硅基移动的α-硅基-炔基化合物，以形成明确的硅基取代的烯丙基络合物，有望以高选择性的方式反应。通过这种方式，用于聚酮结构的重要的共酰化构筑基团的炔衍生库将被扩展。

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.