Enantioselective Synthesis of Spirocyclopentane Oxindoles Bearing Five Consecutive Stereocenters through Secondary Amine-Catalyzed [3+2] Cycloaddition

This work delineates a Michael-initiated ring-closing [3+2] cycloaddition of newly designed 3-(1-benzyl-2-oxoindolin-3-yl)pentane-2,4-diones with alpha,beta-unsaturated aldehydes. During the chiral secondary amine-catalyzed cascade reaction, highly functionalized spirocyclopentane oxindole derivatives containing five consecutive stereogenic centers were formed, two of which were tetrasubstituted carbon. All the desired products are smoothly obtained in good yields (up to 90 %) with excellent enantioselectivities (up to >99 : 1 er) and diastereoselectivities (up to >95 : 5 dr). Meanwhile, the practicality of this strategy was highlighted by the further gram-scale experiment and a set of synthetic transformations.

Automated summary

This work presents a newly designed strategy for a Michael-initiated ring-closing [3+2] cycloaddition reaction between 3-(1-benzyl-2-oxoindolin-3-yl)pentane-2,4-diones and alpha,beta-unsaturated aldehydes. The reaction, catalyzed by a chiral secondary amine, efficiently produces highly functionalized spirocyclopentane oxindole derivatives with five consecutive stereogenic centers, including two tetrasubstituted carbons. The desired products are obtained with high yields, excellent enantioselectivities, and diastereoselectivities. Furthermore, this strategy demonstrates practicality through gram-scale experiments and a series of synthetic transformations.