Edge-to-face CH/pi aromatic interaction and molecular self-recognition in epi-cinchona-based bifunctional thiourea organocatalysis

The impact of cooperativity between intermolecular interactions is demonstrated by the molecular self-recognition properties of highly enantioselective epi-cinchona bifunctional thiourea organocatalysts. Low-temperature NMR experiments in inert solvents have revealed two sets of nonequivalent resonances in equal population for thiourea-modified members of the epi-quinine and epi-quinidine families. In solution, the predominance of an asymmetric (C1) dimeric self-assembly with noteworthy structural motifs became evident: simultaneous intra- and intermolecular thiourea hydrogen bonding and a CH/pi interaction were observed. Both the stereochemical and the diverse conformational features of the system favor the observed quinoline T-shaped aromatic pi-pi stacking interaction. The structure findings are supported by quantitative proton-proton distance data that were available from NOE buildup curves. The 3D structure of the dimeric assembly has been modeled in agreement with the H-H distance restraints. Owing to the geometrical preference associated with the dimerization process, the self-assembled bifunctional system is interpreted as a charge-transfer complex with the potential for catalyst self-activation.