Highly stereo- and enantio‑selective synthesis of spiro cyclopropyl oxindoles via organic catalyst-mediated cyclopropanation

Spiro-cyclopropyl oxindoles are widely found in natural products and medicinal molecules. Herein, we report a highly stereo- and enantio‑selective procedure for accessing this class of compounds via tertiary amine mediated cyclopropanation of ammonium ylides with the in-situ Heck reaction-generated 3-alkenyl indolones as the Michael receptors. This reaction features mild conditions, excellent enantioselectivity (up to 98%) and diastereoselectivity (up to 99:1), high atom- and step-economy, broad substrate scopes, and good functional group tolerance. Additionally, this scalable synthetic process could offer a novel strategy for the efficient synthesis of enantiopure spirocyclopropyl oxindoles. A practical one-pot asymmetric cyclopropanation process for synthesis of spirocyclopropyl oxindoles mediated by recyclable (chiral) tertiary amine catalyst was developed. This protocol is distinguished by its high enantio‑ and diastereoselectivity, the use of readily available starting materials with excellent functional group tolerance, and cost-effective catalyst. Computational studies were conducted, corroborating the experimental findings and confirming the high stereo- and enantioselectivity of the reaction.