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.