Organocatalytic Asymmetric Synthesis of Oxindole-Based Bridged Biaryls

Oxindoles represent privileged structural motifs that are widely distributed among biologically active molecules and natural products; consequently, their asymmetric synthesis has attracted significant attention. On the other hand, bridged biaryls constitute an important yet underexplored class of molecules that exhibit both central and axial chirality simultaneously. Despite their synthetic and structural relevance, methods for the enantioselective construction of oxindole-based bridged biaryls have not yet been reported. Herein, we disclose an organocatalyzed enantio- and diastereoselective strategy for the synthesis of oxindole-fused biaryl-bridged seven-membered carbocyclic scaffolds. Upon activation by a bifunctional organocatalyst, isatin derivatives bearing an ortho-formyl aryl substituent at the C4 position undergo a cascade double aldol or double Henry reaction from the same carbon center of nucleophilic carbonyl compounds or nitroalkanes. This protocol enables the efficient construction of a class of biaryl frameworks featuring three contiguous stereocenters and a chiral axis, delivering the products in high yields and with high enantioselectivities for a broad range of substrates under mild reaction conditions.