Enantioswitching Catalysis with a Single Chiral Organocatalyst

Significance

The enantiodivergent catalysis is an interesting phenomenon, which can selectively afford either enantiomer using a single chiral catalyst. However, in the area of organocatalysis, only a few examples are reported by using stoichiometric chiral promoters or achiral additives. In this report, the authors report a Mannich reaction catalyzed by flexible guanidine/bisthiourea catalyst 1. Various aromatic N-Boc imines could be transformed to (S)- or (R)-2 with high enantioselectivities [(S)-2: er up to 98.5:1.5, (R)-2: er up to 5.5:94.5] by changing the solvent and reaction temperature. Kinetics in different solvents showed that S-selective reactions (in non-polar solvents) are dependent on the differential activation entropies. On the other hand, R-selective reactions were mainly affected by the enthalpy term as usual in asymmetric catalysis. Additionally, catalyst 1 showed high reactivity in non-polar and polar solvents (TOF = 66 h^-¹ in m-xylene, 25 h^-¹ in acetonitrile).