Organocatalysis, catalysis using small organic molecules, has recently evolved into a general approach for asymmetric synthesis, complementing both metal catalysis and biocatalysis. Its success relies to a large extent upon the introduction of novel and generic activation modes. Remarkably though, while carboxylic acids have been used as catalyst directing groups in supramolecular transition-metal catalysis, 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.

The combined activity of (S)-proline and an achiral cocatalyst (a TBD-derived guanidinium salt) allow direct aldol reactions to be carried out with high diastereoselectivity and enantioselectivity under solvent-free conditions with a rather simple reaction setup where stirring is not required.

Oxone, a cheap, stable, and nonhazardous oxidizing reagent, transforms α,β-unsaturated ketones of defined stereochemistry into their corresponding vinyl acetates through a Baeyer-Villiger reaction. This process is general and straightforward, tolerating a wide range of functional groups.

Ready salted proline: The combination of proline and an achiral triazabicyclodecene‐derived guanidinium salt permits, for the first time, the direct aldol reaction of chloroacetone and aromatic aldehydes (see scheme). The resulting chlorohydrins are formed with high regio‐, diastereo‐ and enantioselectivity. This procedure is experimentally simple and green, working without solvent, in test tubes placed inside a standard laboratory fridge without agitation or mechanical stirring.

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