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.