Effective asymmetric vinylogous Mannich reaction of isatin imines with α,α-dicyanoolefins in the presence of a simple chiral amide phosphonium bifunctional phase transfer catalyst

Abstract

An asymmetric vinylogous Mannich reaction between α,α-dicyanoolefins and N-Boc isatin imines has been developed by employing 1 mol% bifunctional amide phosphonium salt as a phase transfer catalyst and K₂CO₃ as a base. When α,α-dicyanoolefins derived from aryl methyl ketones were used as substrates, the normal Mannich adducts of 3,3-disubstituted aminooxindoles were obtained in good to excellent yields with high ee values, while α,α-dicyanoolefins derived from tetralone, propiophenone and methyl tert-butyl ketone led to cyclized products through a cascade sequence of Mannich reaction and intramolecular cyclization. The α,α-dicyanoolefin moiety in the Mannich adduct may be used as an aryl methyl ketone surrogate and the corresponding 3,3-disubstituted aminooxindole ketones may be effectively obtained after removal of the malonic nitrile by KMnO₄ oxidation on a gram scale.