The mechanism of the enantioselective
sulfa-Michael addition reaction
catalyzed by a cinchona alkaloid-squaramide bifunctional organocatalyst
was studied using density functional theory (DFT). Four possible modes
of dual activation mechanism via hydrogen bonds were considered. Our
study showed that Houk’s bifunctional Brønsted acid–hydrogen
bonding model, which works for cinchonidine or cinchona alkaloid-urea
catalyzed sulfa-Michael addition reactions, also applies to the catalytic
system under investigation. In addition, we examined the origin of
the stereoselectivity by identifying stereocontrolling transition
states. Distortion–interaction analysis revealed that attractive
interaction between the substrates and catalyst in the C–S
bond forming transition state is the key reason for stereoinduction
in this catalytic reaction. Noncovalent interaction (NCI) analysis
showed that a series of more favorable cooperative noncovalent interactions,
namely, hydrogen bond, π-stacking, and C–H···π
interaction and C–H···F interactions, in the
major <i>R</i>-inducing transition state. The predicted
enantiometric excess is in good accord with the observed value
