Asymmetric Organocatalysts

Asymmetric catalysis is a method of achieving asymmetric synthesis by using a chiral catalyst. Chiral catalysts are catalysts containing chiral C atoms, which play a pivotal role in some synthetic reactions. Asymmetric synthesis, also known as chiral synthesis, stereoselective synthesis, and enantioselective synthesis, is an organic synthesis branch that studies the chemical reaction of introducing one or more chiral elements into a reactant. According to the definition of Morrison and Mosher, asymmetric synthesis is "an organic reaction in which an achiral unit in the bulk of a substrate molecule is converted into a chiral unit by a reactant that produces a stereoisomer in an unequal amount." Here, the reactant can be a catalyst, a chemical reagent, a solvent or a physical factor. Asymmetric organocatalysts are catalysts that catalyze an asymmetric organic reaction.

Classification

Asymmetric organocatalysts are generally stable in nature, cheap and readily available, non-toxic, and have asymmetric synthetic potentials for chiral activity. The types of asymmetric organocatalysts are extremely diverse. According to the type of reaction, they can be divided into asymmetric catalytic hydrogenation organocatalysts, asymmetric catalytic oxidation organocatalysts, non-dihydroxylation organocatalysts, asymmetric hydroxylation organocatalysts, asymmetric catalytic cyclopropanation organocatalysts, and asymmetric hydrocyanide organocatalysts.

Applications

Asymmetric organocatalysts have a wide range of applications in the synthesis field, and one of the most common applications is to catalyze the Michael addition reaction. The Michael addition reaction is one of the easiest ways to construct a C-C bond, through which many important intermediates can be synthesized. In addition, there are asymmetric catalytic hydrogenation reactions, asymmetric catalytic oxidation reactions, asymmetric catalytic carbonyl reduction reactions and so on.

• Organic catalyzed asymmetric Michael addition reaction: Organic catalysts have a wide range of applications in the field of synthesis. A research group used L-valine as a catalyst in the Aldol reaction of aldehyde and acetone to obtain a target product having enantioselectivity of 96%. Other researchers used N-methyl imidazolidine as a catalyst in an asymmetric Diels-Alde reaction to obtain the target product with enantioselectivity of up to 94%. Encouraged by the excellent catalytic effects of these two asymmetric organocatalysts, more and more chemists have invested in organic catalysis. The organic catalysis has also been rapidly developed, and various novel catalysts have been developed for use in various asymmetric reactions.

  Figure 1. L-valine catalyzed asymmetric Michael addition reaction

• Asymmetric catalytic carbonyl reduction: Some scholars have used oxazol borane as a catalyst to prepare chiral α-hydroxy acids and chiral α-amino acids. Other researchers have used chiral borane to asymmetrically reduce ketones to produce chiral alcohols, and then further react to obtain water-soluble carbonic anhydrase blocker MK-0417, which reduces intraocular pressure and is used to treat glaucoma disease.
• Asymmetric catalytic oxidation reaction: A chiral complex formed by a tetradentate nitrogen organic ligand and a metal manganese compound is used as a catalyst, and hydrogen peroxide is used as an oxidant to asymmetrically catalyze the oxidation of thioether to obtain a corresponding chiral sub Sulfone compound.
• Asymmetric catalytic hydrogenation：Asymmetric catalytic hydrogenation is the conversion of prochiral substrates such as olefins, imines and ketones containing carbon-carbon, carbon-nitrogen and carbon-oxygen double bonds into chirality under the action of a chiral catalyst. The reaction of a product containing hydrogen in the center. Some researchers have prepared chiral phosphine-oxazoline catalysts for asymmetric hydrogenation.

References

1. Dalko, P. L; Moisan, L. ( 2001).”Enantioselective organocatalysis.” Angew. Chem. Int. Ed. 40, 3726-3748.
2. Marckwald, W. Ueber (1904).”Asymmetrische Synthese.” Berichte der Deutschen chemischen Gesellschaft., 37,349-354.
3. List, B., Lerner, R. A., Barbas, (2000) ”Proline-catalyzed direct asymmetric aldol reactions.” J. Am. Chem. Soc. ,122, 2395-2396.