Catalytic, enantioselective alkylation of 1-azaallyl cations with silylketene acetals

• Applicant: Professor Dr. Christoph Schneider
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545921106

Umpolung reactions are highly valuable transformations in organic chemistry as they furnish products with an unusual functional group pattern. In particular, the stereoselective synthesis of 1,4-dicarbonyl compounds is of great importance for further elaboration e. g. towards highly substituted 5-membered heterocycles. In this project we intend to develop and study broadly the first catalytic, enantio- and diastereoselective synthesis of 1,4-(hetero)-dicarbonyl compounds carrying up to two new stereogenic centers. a-Acetoxy hydrazones are envisaged to be converted into transient, resonance-stabilized 1 azaallyl cations through silyliumion Lewis acids and subsequently trapped with silylketene acetals and related compounds. Pursuing this concept the normal nucleophilic reactivity of (aza-)enolates will be inverted into an electrophilic reactivity of enolonium-type 1-azaallyl cations. The enantioselectivity of the reaction will be controlled by the chiral anion of the silyliumion Lewis acid. As guiding principle we intend to employ precatalysts of the IDPI-type which have already shown great promise in the preliminary work and gave rise to excellent enantioselectivity in reactions with the acetate-based silylketene acetal. Substituted silylketene acetals are envisaged to generate a second stereogenic center in the products diastereoselectively. Moreover, N,O-silylketene acetals and silylketene imines will be studied as additional nucleophiles to further broaden the scope of the reaction. Vinylsilylketene acetals offer the possibility for a vinylogous reaction pathway and should provide valuable 1,6-(hetero)-dicarbonyl compounds with up to two new chiral centers. Finally, the synthetic potential of the products will be demonstrated through conversion of some of the products into substituted, enantiomerically highly enriched pyrrolidines.

• DFG Programme: Research Grants