Access to Chiral 2,5-Pyrrolidinyl Dispirooxindoles via Dinuclear Zinc-Catalyzed Asymmetric Cascade Reactions

J Org Chem. 2019 Jun 21;84(12):7762-7775. doi: 10.1021/acs.joc.9b00645. Epub 2019 Jun 13.

Abstract

A series of new nonsymmetric semi-azacrown ether ligands were developed and applied to the asymmetric Michael/cyclic keto-imine formation/Friedel-Crafts alkylation reactions of 3-amino oxindole hydrochlorides and β,γ-unsaturated α-keto amides. A diversity of 2,5-pyrrolidinyl dispirooxindoles containing two nonadjacent spiro-quaternary stereocenters were obtained in excellent diastereoselectivities and moderate to excellent enantioselectivities (up to 95% ee). A possible catalytic cycle was proposed to explain the origin of the asymmetric induction.