Regio- and diastereoselective construction of conjugate oxindole derivatives enabled by delayed acyl transfer of pyridinium ylides

Abstract

Regio- and diastereoselective construction of conjugate oxindole moieties has been a daunting challenge in the synthetic community. Herein, we design and develop a one-pot cascade strategy for the assembly of multi-substituted conjugate oxindole derivatives. This methodology involves a rhodium-catalyzed aldol-type interception of pyridinium ylides followed by intramolecular delayed acyl transfer and elimination to deliver the targeted molecules. This approach represents a new reaction mode for carbene gem-difunctionalization by delayed acyl transfer instead of delayed proton transfer. The protocol proceeds under mild reaction conditions, exhibits excellent functional group tolerance and affords products in good yields with high diastereoselectivities. Furthermore, a preliminary antitumor activity study of these conjugate oxindole products indicates that the generated product 4cj exhibites high anticancer potency against HCT-116 cells (IC₅₀ < 1 μM).