Dinuclear zinc-catalyzed asymmetric [3+2] cyclization reaction for direct assembly of chiral α-amino-γ-butyrolactones bearing three stereocenters

An efficient enantioselective [3 + 2] annulation of alpha-hydroxy-1-indanones and alkylidene azlactones has been developed with chiral dinuclear zinc catalysts via a Bronsted base and Lewis acid cooperative activation model. This practical methodology gives access to a broad range of chiral alpha-amino-gamma-butyrolactones bearing three stereocenters in good yields with excellent diastereo- and enatiostereoselectivities (up to 88% yield, 20 : 1 dr, 99% ee). This transformation features broad functional group tolerance, gram-scale synthesis, and further prolongation with alpha-hydroxyacetophenone or 3-hydroxychroman-4-one.

Automated summary

An efficient enantioselective [3 + 2] annulation of alpha-hydroxy-1-indanones and alkylidene azlactones has been developed with chiral dinuclear zinc catalysts via a Bronsted base and Lewis acid cooperative activation model, allowing for the synthesis of a broad range of chiral alpha-amino-gamma-butyrolactones with three stereocenters in good yields and excellent diastereo- and enatiostereoselectivities.