Enantioselective Organocatalysis

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Abstract
The last few years have witnessed a spectacular advancement in new catalytic methods based on metal‐free organic molecules. In many cases, these small compounds give rise to extremely high enantioselectivities. Preparative advantages are notable: usually the reactions can be performed under an aerobic atmosphere with wet solvents. The catalysts are inexpensive and they are often more stable than enzymes or other bioorganic catalysts. Also, these small organic molecules can be anchored to a solid support and reused more conveniently than organometallic/bioorganic analogues, and show promising adaptability to high‐throughput screening and process chemistry. Herein we focus on four different domains in which organocatalysis has made major advances: 1) The activation of the reaction based on the nucleophilic/electrophilic properties of the catalysts. This type of catalysis has much in common with conventional Lewis acid/base activation by metal complexes. 2) Transformations in which the organic catalyst forms a reactive intermediate: the chiral catalyst is consumed in the reaction and requires regeneration in a parallel catalytic cycle. 3) Phase‐transfer reactions: The chiral catalyst forms a host–guest complex with the substrate and shuttles between the standard organic solvent and the second phase (i.e. a solid, aqueous, or fluorous phase in which the organic transformation takes place). 4) Molecular‐cavity‐accelerated asymmetric transformations: the catalyst can select between competing substrates, depending on size and structure criteria. The rate acceleration of a given reaction is similar to the Lewis acid/base activation and is the consequence of the simultaneous action of different polar functions. Herein it is shown that organocatalysis complements rather than competes with current methods. It offers something conceptually novel and opens new horizons in synthesis.