Asymmetric Organocatalysis

Abstract

Despite considerable efforts to explore and extend the scope of asymmetric organocatalytic reactions throughout the last years, their use in medicinal and process chemistry is still rather low. This minireview highlights some of the recent developments in the rapidly evolving field of organocatalysis recently presented at the Schering Foundation organized symposium on “Organocatalysis”.

Rapid Optical Methods for Enantiomeric Excess Analysis: From Enantioselective Indicator Displacement Assays to Exciton-Coupled Circular Dichroism

“…This is best exemplified in the pharmaceutical industry, where the enantiomer of a bioactive drug could have unforeseeable detrimental effects on humans. Recent advances in asymmetric synthesis have provided a multitude of ways to efficiently obtain one preferred enantiomer over the other . These asymmetric transformations are often carried out with either a chiral catalyst or chiral auxiliary. , One method of chiral catalyst and auxiliary discovery is high-throughput screening (HTS) where rapid quantification of product enantiomeric excess (ee) and yield is required to achieve high efficiency. , Currently, the use of chiral chromatographic methods is the most common strategy to measure ee values. − These methods are associated with high cost (solvent, column replacement) and low duty cycle (equilibration time) and therefore are not ideal for HTS.…”

“…Recent advances in asymmetric synthesis have provided a multitude of ways to efficiently obtain one preferred enantiomer over the other. 1 These asymmetric transformations are often carried out with either a chiral catalyst or chiral auxiliary. 2,3 One method of chiral catalyst and auxiliary discovery is high-throughput screening (HTS) where rapid quantification of product enantiomeric excess (ee) and yield is required to achieve high efficiency.…”

2.07 The Aldol Reaction: Organocatalysis Approach

“…8 In 2000, the List and Barbas group demonstrated the strategic rediscovery of proline's remarkable ability of type I aldolase mimicking intermolecular organocatalytic direct aldol reaction through the study of aldolase and antibody (see also Scheme 19) After these pioneering research on direct aldol reactions, a number of small metal-free organic molecules as organocatalysts in asymmetric bond-forming reactions and domino reactions have been reported. [10][11][12][13][14][15][16][17] Organocatalysts allow for the enantioselective synthesis of molecules that were not readily available by traditional methods. Research in this area has advanced rapidly over the past decade, and the versatility, simplicity, and safety of organocatalytic reactions have been demonstrated.…”

A Multistep Organocatalysis Experiment for the Undergraduate Organic Laboratory: An Enantioselective Aldol Reaction Catalyzed by Methyl Prolinamide

“…Enantioselective organocatalysis has become a field of central importance for the asymmetric synthesis of chiral molecules. A number of extensive reviews and books have been published in recent years that show the wide applicability of this field. − Despite this explosion in organocatalysis, few articles have been published applying this new field of research in the undergraduate organic chemistry curriculum. − Two of these involve the direct use of a commercially available amino acid, ( S )-proline for an aldol and Robinson annulation reaction, respectively. , The other example is the synthesis of warfarin using the commercially available enantiomers of 1,2-diphenylethylenediamine . We have developed a multistep synthesis organic chemistry capstone project, based on recent developments in this area, in which the students synthesize an organocatalyst that is then utilized in an enantioselective organocatalytic aldol reaction.…”