Organocatalysis Intermediates as Platforms to Study Noncovalent Interactions: Integrating Fluorine Gauche Effects in Iminium Systems to Facilitate Acyclic Conformational Control

Achieving acyclic conformational control over several bonds has been realized by the strategic installation of a vicinal difluoroethane bridge in a generic proline-derived organocatalyst. The torsion angle phi(FCCF) is governed by stabilizing hyperconjugative interactions (sigma sigma*), thus ensuring a 60 degrees relationship. This effect has been telescoped by positioning a stereogenic fluorine center proximal to the nucleophilic amine. Upon iminium formation, this center is rendered electron deficient, thus triggering a dynamic fluorine iminium ion gauche effect. Consequently, conformational control over five atoms and four bonds can be achieved by reversible formation of an iminium -bond.