The metal (ion)-free catalysis of organic reactions is a contemporary challenge that is just being taken up by chemists. Hence, this field is in its infancy and is briefly reviewed here, along with some rough guidelines and concepts for further catalyst development. Catalysis through explicit hydrogen bonding interactions offers attractive alternatives to metal (ion)-catalyzed reactions by combining supramolecular recognition with chemical transformations in an environmentally benign fashion. Although the catalytic rate accelerations relative to uncatalyzed reactions are often considerably less than for the metal (ion)-catalyzed variants, this need not be a disadvantage. Also, owing to weaker enthalpic binding interactions, product inhibition is rarely a problem and hydrogen bond additives are truly catalytic, even in water.

The present critical review outlines the close relationship and mutual interplay between molecular recognition, active site considerations in enzyme catalysis involving anions, and organocatalysis utilizing explicit hydrogen bonding. These interconnections are generally not made although, as we demonstrate, they are quite apparent as exemplified with pertinent examples in the field of (thio)urea organocatalysis. Indeed, the concepts of anion binding or binding with negatively (partially) charged heteroatoms is key for designing new organocatalytic transformations. Utilizing anions through recognition with hydrogen-bonding organocatalysts is still in its infancy but bears great potential. In turn, the discovery and mechanistic elucidation of such reactions is likely to improve the understanding of enzyme active sites (108 references).