Three-Component Cyclobutylation via Silver(I)-Catalyzed Carbene Transfer Reactions with [1.1.1]Propellane

In this study, we report an innovative Ag(I)-catalyzed carbene transfer reaction that employs [1.1.1]propellane as a precursor to form the methylene cyclobutyl carbene complex for a controllable three-component reaction. The key strategy of this method involves the formation of Ag-bound oxonium ions as intermediates, which are generated by the reaction between the Ag-carbene complex and cyclic ether-type solvents such as THF and 1,4-dioxane. The subsequent nucleophile-induced C-O bond cleavage leads to a three-component etherification of methylene cyclobutane. Employing this strategy, we successfully coupled various amine and alcohol partners, demonstrating the method's potential for the late-stage functionalization of intricate, biologically relevant molecules and synthetic manipulations of the resulting products. To further explore the mechanism driving selective three-component reactions, we have conducted comprehensive experimental and computational studies.

Automated summary

In this study, an innovative Ag(I)-catalyzed carbene transfer reaction using [1.1.1]propellane as a precursor was reported. The method involves the formation of Ag-bound oxonium ions as intermediates through the reaction between the Ag-carbene complex and cyclic ether-type solvents. The subsequent nucleophile-induced C-O bond cleavage leads to a controllable three-component etherification of methylene cyclobutane. The method demonstrates potential for the late-stage functionalization of complex, biologically relevant molecules and synthetic manipulations of the resulting products.