title: Cinchona Alkaloid-Squaramide Catalyzed Sulfa-Michael Addition Reaction: Mode of Bifunctional Activation and Origin of Stereoinduction.
abstract: 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 R-inducing transition state. The predicted enantiometric excess is in good accord with the observed value.
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore , 28 Medical Drive, Singapore 117456.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Guo
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore , 28 Medical Drive, Singapore 117456.|Department of Chemistry, National University of Singapore , 3 Science Drive 3, Singapore 117543.
authors.forename: Ming Wah
authors.identifier: 0000-0003-2162-1220
authors.initials: MW
authors.lastname: Wong