Nitrile-Stabilized Quaternary Ammonium Ylide as an Arylcyanomethylene Transfer Agent: Diastereoselective Synthesis of Spiro-Cyanocyclopropyl-2-Oxindoles

Nitrile-stabilized quaternary ammonium ylide as an effective aryl-cyanomethylene transfer agent has been explored for the first time, which enables a spirocyclopropanation process with conjugated carboxamide of indole heterocycle. The developed In(OTf)3-catalyzed method provides a straightforward, diastereoselective access to pharmaceutically relevant spiro-cyclopropane-2-oxindole skeleton assembled with an alpha-cyano and two (hetero)aromatic substitutions. The common difficulties of a cyclopropanation process, e. g., a conjugated carboxamide as valid substrate, cleavage-susceptibility of amide bond, substrates scope limited to preferentially electron-withdrawing group containing molecules, and the competing dehydrocyanation reaction of product generated from nitrile-stabilized ylide have been overcome in the present spirocyclopropanation process. A diastereoselective cyclopropanation of nitrile-stabilized quaternary ammonium ylide with a weakly activated conjugated carboxamide functional motif is reported, which provides an efficient access to biologically relevant spiro-cyanocyclopropane oxindoles, while sigmatropic rearrangement process of the ylide is commonly known. image