Pentafluorophenyl‐Substituted Proline‐Derived Chiral Urea for “On Water” Asymmetric Hydrogen‐Bonding Catalysis

Abstract

AbstractThis work demonstrated the efficacy of a proline‐derived chiral urea for “on water” asymmetric hydrogen‐bonding catalysis by incorporating a hydrophobic and electron‐withdrawing pentafluoro‐phenyl substituent into the urea moiety. When employed as a catalyst, pentafluorophenyl‐substituted proline‐derived chiral urea exhibited significant enhancement of both the reaction rate and stereoselectivity when conducted “on water” compared to that of conventional organic solvents due to the hydrophobic hydration effect. Moreover, this catalyst did not display notable self‐aggregation during the “on water” hydrogen‐bonding catalysis and was confirmed to exist as a monomeric species with catalytic activity. Due to its remarkable acceleration in “on water” conditions, the catalyst load was significantly reduced. Consequently, complete conversion was achieved at room temperature within 2 hours while maintaining good enantioselectivities (up to 96% ee) even at 0.2 mol% catalyst loading in the Michael addition of dithiomalonate to nitrostyrene.