Selective acceleration of disfavored enolate addition reactions by anion-π interactions

In chemistry and biology, cation-pi interactions contribute significantly to many important transformations. In sharp contrast, reactions accomplished with support from the complementary anion-pi interactions are essentially unknown. In this report, we show that anion-pi interactions can determine the selectivity of the enolate chemistry of malonate half thioesters. Their addition to enolate acceptors is central in natural product biosynthesis but fails without enzymes because non-productive decarboxylation dominates. The newly designed and synthesized anion-pi tweezers invert this selectivity by accelerating the disfavored and decelerating the favored process. The discrimination of anionic tautomers of different planarization and charge delocalization on pi-acidic surfaces is expected to account for this intriguing "tortoise-andhare catalysis." Almost exponentially increasing selectivity with increasing pi acidity of the catalyst supports that contributions from anion-pi interactions are decisive.