Asymmetric synthesis

Asymmetric synthesis is a type of stereoselective reaction in which a new chiral stereogenic unit is formed during the process. A chiral center, chiral axis, or chiral plane can be used as the new stereogenic unit. The reaction must proceed with the synthesis of stereoisomers in unequal amounts. Prochiral units, such as a prochiral center, a prochiral plane, or a prochiral axis, can be used to make the chiral unit. Enantiotopic or diastereotopic prochiral units are possible. As a result, there are two key components in asymmetric synthesis:

• A prochiral unit is converted to a chiral unit; and
• Unequal proportions of potential chiral stereoisomers are formed.

Why is asymmetric synthesis important?

Because biological systems, where they are intended for application, are also chiral, it is critical to synthesize single enantiomers of chiral compounds. Different enantiomers interact with biological receptors in varied ways resulting in very different responses. Different enantiomers of molecules have diverse biological activity, and asymmetric synthesis is a viable method for producing stereoisomeric drugs for medicinal uses.

In chemical science adoption of efficient asymmetric synthesis, methodologies are required to obtain enantiomerically pure compounds for biological purposes such as medicines, sweeteners, and moisturizers.

Asymmetric catalysis

Asymmetric catalysis is a type of catalysis in which a chiral catalyst controls the synthesis of a chiral molecule so that one stereoisomer is formed more frequently. Because the catalyst is not consumed in this process, it can be employed in a substoichiometric amount, increasing efficiency and reducing waste.

Asymmetric catalysis involving organometallic species is rapidly progressing, and specific systems are now stereoselective enough for practical use. Asymmetric chemical catalysts provide the greatest promise for universal asymmetric synthesis since they have essentially no limits in terms of molecular design, other than those imposed by the human who designed them, or in terms of chemical science, reactions can be done asymmetrically.

Strategies of asymmetrical synthesis in chemical science

Chemical science has two primary asymmetric synthesis methodologies that will be discussed:

• Chiral pool synthesis or chiron approach
• Chiral auxiliary approach

Chiral pool synthesis

A chiral pool synthesis is an approach for increasing chiral synthesis efficiency. A store of readily available enantiopure chemicals begins the organic synthesis of a complex enantiopure chemical molecule. Monosaccharides and amino acids are common chiral starting materials. The built-in chirality is then kept throughout the rest of the chemical reaction.

This approach is beneficial if the desired molecule looks like cheap enantiopure natural goods. Otherwise, an extended tortuous synthesis with numerous steps and yield losses may be necessary.

Chiral auxiliary approach

Chiral auxiliaries are the pure substances obtained mostly from chiral sources that are inexpensive. Second-generation asymmetric synthesis refers to the employment of a chiral auxiliary in asymmetric synthesis. A stoichiometric chiral based auxiliary is strongly linked to the substrate in this method, which is then followed by a diastereoselective reaction in which the chirality of auxiliary governs the asymmetric induction. The auxiliary is removed and recycled after the new chiral center is set up.

Classification of methods

The known methods of asymmetric synthesis may be classified into four-generation –

First-generation

Diastereoselective reactions in which an existing chiral center in the same molecule controls the synthesis of a new chiral center. Substrate-controlled diastereoselectivity is a term used to describe this phenomenon.

Second generation

An achiral substrate is chiralized by adding a chiral auxiliary, which then directs subsequent reactions before being removed to yield the chiral product. This approach has the additional benefit of collecting and recycling the auxiliary. Still, it also has the disadvantage of requiring two additional synthetic steps, one to introduce the auxiliary and the other to remove it.

Third generation

chiral allylmetals are added to achiral aldehydes. Reagent control is a method of preferentially generating one stereoisomer out of many in organic synthesis, with the stereoselectivity defined by the structure and chirality of the reagent utilized. When chiral reagents approach prochiral faces or groups on a molecule, they can create energetically distinct TS’s, allowing them to perform enantioselective reactions DIRECTLY on an achiral starting material.

Fourth generation

Catalytic modifications of second-and third-generation approaches are frequently grouped as fourth-generation strategies. In a catalytic cycle intermediate, the chiral auxiliary and other catalytic components, such as a transition metal, can become covalently linked to the substrate.

Terminology of asymmetric synthesis

Asymmetric induction

Asymmetric induction is the regulation of stereoselectivity on developing a new chiral center by an existing chiral center. This is a characteristic shared by several asymmetric synthesis techniques. The goal is to make diastereomers out of enantiomers. Because diastereomers have differing reactivities, one diastereomer will develop preferentially. Substantial enantiomeric excesses can be obtained using a chiral auxiliary with a high asymmetric induction.

Enantiomeric excess

The enantiomeric excess, commonly represented as a percentage of the total, is referred as the one enantiomer over the other generated in an enantioselective reaction. It usually gives a measure of the enantioselective reaction’s efficiency.

Conclusion

Asymmetric synthesis is only conceivable when the reaction’s possible transition states are diastereomeric because they have different energies and produce products at different rates.