Asymmetric Synthesis of Spiro[3,2′-morpholine-oxindoles] Derivatives via the [5+1] Annulation Reaction

An efficacious method in which BINOL-type chiral imidodiphosphoric acid catalyzed the asymmetric [5 + 1] annulation reaction of 2-pyrrolylphenol with 1-methylindoline-2,3-dione was established. The strategy tolerated a broad substrate scope, and 30 examples were obtained. A range of enantioenriched spiro[3,2'-morpholine-oxindole] derivatives which incorporate a tertiary stereocenter, with moderate to excellent yields (up to 96%) and enantioselectivities (up to 99%) under mild conditions, was delivered.

Automated summary

An efficacious method utilizing BINOL-type chiral imidodiphosphoric acid as catalyst was developed for the asymmetric [5 + 1] annulation reaction between 2-pyrrolylphenol and 1-methylindoline-2,3-dione, leading to a range of enantioenriched spiro[3,2'-morpholine-oxindole] derivatives incorporating a tertiary stereocenter with moderate to excellent yields and enantioselectivities under mild conditions.