Activation of Carboxylic Acids in Asymmetric Organocatalysis

Organocatalysis, catalysis using small organic molecules, has recently evolved into a general approach for asymmetric synthesis, complementing both metal catalysis and biocatalysis. 1 Its success relies to a large extent upon the introduction of novel and generic activation modes. 2 Remarkably though, while carboxylic acids have been used as catalyst directing groups in supramolecular transition‐metal catalysis, 3 a general and well‐defined activation mode for this useful and abundant substance class is still lacking. Herein we propose the heterodimeric association of carboxylic acids with chiral phosphoric acid catalysts as a new activation principle for organocatalysis. This self‐assembly increases both the acidity of the phosphoric acid catalyst and the reactivity of the carboxylic acid. To illustrate this principle, we apply our concept in a general and highly enantioselective catalytic aziridine‐opening reaction with carboxylic acids as nucleophiles.