The types of hydrogen-bond donors used in catalysis vary widely from reaction to reaction, even among similar catalytic strategies. While specific systems are often studied and optimized extensively, a general understanding of the optimal donor for a reaction or the relationship between catalyst structure and reactivity is greatly lacking. It is not yet practical to rationally design structures to promote a desired reaction with the desired selectivity. However, contemporary hydrogen-bond catalysis is primarily focused on a few types of systems that experimentally seem to be effective in a variety of situations. These are termed "privileged structures". However, it is worth noting that other structural scaffolds and motifs have also shown promising results, such as metal-coordinated hydrogen-bond donors.
*Ureas and thioureas are by far the most common structures and can stabilize a variety of negatively charged intermediates, as well as engage in anion-binding catalysis. Bifunctional urea and thiourea catalysis are abundant in the literature. Thioureas are often found to be stronger hydrogen-bond donors (i.e., more acidic) than ureas because their amino groups are more positively charged. Quantum chemical analyses revealed that this counterintuitive phenomenon, which is not explainable by the relative electronegativities of O and S, results from the effective steric size of the chalcogen atoms.
*Guanidinium and amidinium ions are structural relatives of ureas and thioureas and can catalyze similar reactions but, by virtue of their positive charge, are stronger donors and much more acidic. The mechanism of guanidinium and amidinium catalysis is thought to often involve partial protonation of substrate.
*Diol catalysts are thought to engage substrate with a single hydrogen bond, with the other hydroxyl participating in an internal hydrogen bond. These are some of the earliest hydrogen-bond catalysts investigated. They are most commonly used in stabilizing partial anionic charge in transition states, for example coordinating to aldehyde dienophiles in hetero-Diels-Alder reactions.
*Phosphoric acid catalysts are the most common strong acid catalysts and work by formation of chiral ion pairs with basic substrates such as imines.