The structural elucidation of chiral rare-earth-based
catalysts
in asymmetric reactions holds significant importance as it is crucial
for comprehending their operational mechanisms and for broadening
their applications in the realm of asymmetric synthesis. Herein, a
LaIII/(L3-RaMe3)2 complex was identified to
be more active and enantioselective than LaIII/L3-RaMe3 in the asymmetric formal substitution of racemic 3-bromo-3-substituted
oxindoles with TMSCN. The experimental studies and theoretical calculations
disclosed that the partial dissociation of the chiral N,N′-dioxide ligand was involved in the catalytic
process with LaIII/(L3-RaMe3)2. These insights
provided a rationale for the remarkable effect of catalyst structures
on the results and nonlinear effect observed in the current reaction
system. This protocol offers a straightforward and efficient pathway
to synthesize various chiral 3-cyano-3-substituted oxindoles (53 examples,
up to 99% yield, 98% ee). In addition, the synthesis of a bioactive
compound CRTH2 receptor antagonist and obvious inhibitory effect of
several products on the viability of cancer cells demonstrate the
potential utility of this methodology.