Organocatalytic Tandem Reaction to Construct Six-Membered Spirocyclic Oxindoles with Multiple Chiral Centres through a Formal [2+2+2] Annulation

An efficient tandem reaction for the asymmetric synthesis of six-membered spirocyclic oxindoles has been successfully developed through a formal [2+ 2+2] annulation strategy. The amine-catalysed stereoselective Michael addition of aliphatic aldehydes to electron-deficient olefinic oxindole motifs gave chiral C3 components, which were further combined with diverse electrophiles (activated olefins or imines) to afford spirocyclic oxindoles with versatile molecular complexity (up to six contiguous stereogenic centres, high diastereo- and enantioselectivities).