Dual Brønsted‐acid Organocatalysis: Cooperative Asymmetric Catalysis with Combined Phosphoric and Carboxylic Acids

How can an assisting Brønsted‐acid be beneficial in asymmetric Brønsted‐acid catalysis? In this Minireview, we discuss selected examples of chiral organocatalysts that feature two acidic groups working cooperatively by virtue of intra‐ or intermolecular hydrogen‐bonding. In these systems, the assisting Brønsted‐acid can play different roles, ranging from simple hydrogen‐bond donation, to substrate‐binding or even as a nucleophilic reaction partner. By analysis of combined experimental, structural and theoretical data, we aim at developing a better understanding of the reaction mechanisms, which are largely influenced by the underlying intramolecular‐ and intermolecular catalyst‐substrate interactions. This may aid in the future development of more selective dual Brønsted‐acid organocatalysts for specific asymmetric transformations. Two are better than one: The use of assisting Brønsted‐acids allows the modulation of reactivities and selectivities of chiral Brønsted‐acid organocatalysts. Experimental and theoretical investigations of the intra‐ and intermolecular hydrogen‐bonding interactions, which play a key role in the reaction mechanisms, are used to develop a better understanding of these combined‐acid catalysts.