Polyether Natural Product Inspired Cascade Cyclizations: Autocatalysis on π-Acidic Aromatic Surfaces.

Anion-π catalysis functions by stabilizing anionic transition states on aromatic π surfaces, thus providing a new approach to molecular transformation. The delocalized nature of anion-π interactions suggests that they serve best in stabilizing long-distance charge displacements. Aiming therefore for an anionic cascade reaction that is as charismatic as the steroid cyclization is for conventional cation-π biocatalysis, reported here is the anion-π-catalyzed epoxide-opening ether cyclizations of oligomers. Only on π-acidic aromatic surfaces having a positive quadrupole moment, such as hexafluorobenzene to naphthalenediimides, do these polyether cascade cyclizations proceed with exceptionally high autocatalysis (rate enhancements kauto /kcat >104  m-1 ). This distinctive characteristic adds complexity to reaction mechanisms (Goldilocks-type substrate concentration dependence, entropy-centered substrate destabilization) and opens intriguing perspectives for future developments.