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

Abstract

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 α‐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.