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

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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.