The past few decades have witnessed some of the most important and revolutionizing advances in the field of asymmetric catalysis. Chemists no longer rely solely on natural sources as the starting point of their synthetic strategy, as in chiral pool or auxiliary-based synthesis. Instead, naturally occurring chiral motifs are selected and, either unchanged or after modification, used in substoichiometric amounts as chiral catalysts or ligands. In this way, they effectively transfer their chirality to prochiral substrates, thereby rapidly amplifying and diversifying the arsenal of useful chiral building blocks available to the synthetic community. A long-standing goal in the pursuit of new catalytic systems is the discovery of general catalysts. Ideally, such catalytic systems should be capable of promoting a large number of enantioselective reactions, via multiple modes of activation, with good substrate tolerance and high stereoselectivity. In this Account, we describe the synthetic usefulness, efficiency, selectivity, and robustness of the diarylprolinol silyl ether system as the catalyst in various reactions of aldehydes. Based on the diarylprolinol silyl ether system, several studies on enamine-mediated transformations of saturated aldehydes have resulted in the introduction of different functionalities into the α-position of aldehydes in a highly stereoselective manner. This HOMO-activation concept was later extended to include α,β-unsaturated aldehydes, which after condensation with the aminocatalyst generate a dienamine species capable of undergoing stereoselective Diels-Alder-type reactions. As a result, the effective functionalization of the γ-position of the aldehyde is achieved. Recently, the activation principle was further developed to include 2,4-dienals, which form trienamine intermediates upon condensation with the aminocatalyst. The trienamines effectively react with carbon-centered dienophiles, forming aldehyde products having up to four contiguous stereocenters. Because of the concerted nature of the reaction and the efficient catalyst shielding of the β-position, the stereoinduction is achieved at the remote ε-position of the original aldehyde. Complementary to the enamine-mediated activations, α,β-unsaturated aldehydes can also be efficiently functionalized by applying the diarylprolinol silyl ether system via conjugate addition through iminium-ion-mediated processes, that is, LUMO-activation. In such reactions, the aminocatalyst not only effectively shields one of the enantiotopic faces of the enal, it also ensures excellent chemoselectivity, affording 1,4-adducts as the only products. Several different carbon and heteroatom nucleophiles can be added in a highly stereoselective fashion. The ability of the catalysts to participate in various enamine- and iminium-ion-mediated processes also makes them ideal for the sequential addition of nucleophiles and electrophiles in a cascade manner. These cascade reactions thereby afford access to products having at least two stereocenters. In the years to come, the diarylprolinol silyl ether catalysts will probably maintain their prominent position as general catalysts in the field of aminocatalysis. Moreover, recent efforts devoted to mechanistic studies might soon engender further advances with this versatile catalytic system, particularly in the areas of activation modes, catalyst loadings, and industrial applications.
