Stereoselectivity is the process in which the formation of one of the stereoisomers is preferred over another during a chemical reaction. In a stereoselective reaction, a single reactant can give two or more products but one of the products is produced in excess. These reactions result in the formation of an unequal mixture of stereoisomers. In fact, it is associated with particular reactions and their mechanisms.
In chemistry, it is a pivotal concept, because the properties and biological activity of a chemical species can be greatly affected by the spatial orientation of bonds. For example, cis-platin is an active anticancerous drug whereas, its stereoisomer, trans-platin is inactive in similar conditions.
It also helps in finding the different mechanisms of the same chemical reaction. Moreover, it is being used to control the yield of the product in the desired way. Furthermore, stereoselective reactions are also used in the synthesis of natural products, such as terpenes and alkaloids, as well as in the production of alkenes to be used in the synthesis of polymers.
In this general example of stereoselectivity, reactant ‘A’ gives two products in different concentrations. This shows that the formation of ‘B’ is preferred over ‘C’ because stereoisomers form in different ratios. So this is a stereoselective reaction.
How can stereoselectivity be achieved in a chemical reaction?
Stereoselectivity can be induced in a reaction through the use of certain reaction conditions. For example, the reactions that take place in a polar solvent will preferentially form one enantiomer over the other due to the effect of solvation on the reactants. This effect is prominent in reactions of primary alcohols.
Additionally, certain reactions that take place under high pressure or high temperature may also exhibit stereoselectivity. For example, in the hydrogenation reaction of alkenes, cis-stereoisomer, as well as trans products, are produced.
However, there are numerous reactions in organic chemistry that exhibit inherent stereoselectivity, which means that the reaction itself has a preference for forming one stereoisomer over the other. This is because of the arrangement of bonds and the steric effects.
Examples of stereoselective reaction(stereoselectivity)
Hydrogenation of cycloalkenes
Catalytic hydrogenation of cyclo alkenes is an example of stereoselective reactions. The cyclo alkenes prefer syn addition to giving less sterically crowded products. Both hydrogens are added from the same face of the Pi (π) bond. This reaction can proceed using a metal atom as a catalyst. One of the stereoisomers forms in a greater ratio than another.
β-elimination reactions are generally stereoselective reactions. It depends upon the availability of β-hydrogen. If two beta hydrogens are available then they result in the formation of cis and trans alkenes. Trans isomer is a major product due to its stability. Whereas cis isomer is a minor product because it is less stable due to steric crowding.
This selective preparation is governed by Zaitsev’s rule, which states that the more substituted product with more substituted carbon is more stable, hence formed in excess.
When acyclic alkenes react with meta-chloroperoxybenzoic acid (m-CPBA), they give stereoselective reactions. Similarly, allylic alcohols can also give a stereoselective reaction when reacting with m-CPBA. For instance, in the reaction given below, a major isomer formed is 95%. This is because m-CPBA attacks a less hindered face and can form hydrogen bonding with the OH group.
Reduction of cyclic ketones
Unhindered ketones normally react with NaBH4 or LiAlH4 and give a mixture of stereoisomers. Usually, the reagent approaches from axial directions and provides an equatorial product (alcohol) in a different ratio.
Stereoselectivity in the reduction of homoallylic Alcohols
Homoallylic alcohols also give a stereoselective reaction in the presence of a rhodium catalyst. There is syn addition of Hydrogen atoms with respect to the hydroxyl (OH) group. For example:
Wittig reaction is also a stereoselective reaction. In this reaction, E and Z isomers are formed. Their concentration depends upon the stability of ylides. With stabilized ylides, E isomer is produced in excess whereas with unstabilized ylides Z isomer is produced in excess.
Enantioselective reactions: Type of Stereoselectivity
When, during a chemical reaction, one enantiomer is preferably formed over another enantiomer, then this reaction is known as an enantioselective reaction. In these reactions one of the enantiomers formed in excess. This is also known as enantiomeric excess. It is represented by ‘ee’.
It involves the formation of the R/S product by using a chiral catalyst.
There are three different types of enantioselective reactions
- Enantioselective addition (Diastereoselective)
- Enantioselective reduction
- Enantioselective hydrosilylation (oxidation)
When one of the diastereomers forms in excess during a chemical reaction, this is also known as a diastereoselective reaction. During these reactions, one diastereomer is preferred over all other possible diastereomers. This will be formed in excess as compared to other diastereomers. This is also known as diastereomeric excess. It is represented by ‘de’.
For example, in the reaction given below, when ketone is reduced by LiAlH4, two diastereomers formed in 3:1. Thus major isomers are three times greater in concentration than the minor product. Note that, in a major diastereomer, hydroxyl (OH) and methyl (CH3) groups are anti to each other.
In the second example below, aldehyde gives diastereoisomers when treated with the Grignard reagent. In this reaction, diastereomer products are produced 3:1. However, the major product is changed, such that the significant diastereomer has OH and CH3 groups that are syn to each other.
What is a stereoselective reaction?
It is the chemical reaction in which two or more stereoisomers are produced but one of the stereoisomers is formed in excess this is called a stereoselective reaction.
How can we find whether a reaction is stereoselective or not?
If a chemical reaction produces two or more stereoisomers and one of the stereoisomers is in excess then this is the stereoselective reaction.
Why does one of the stereoisomers form in excess during stereoselective reactions?
During stereoselective reactions, one stereoisomer is predominantly formed because they have a choice of pathways and one pathway is more favorable than the other.
What makes a reaction stereoselective?
There are different factors that make a reaction stereoselective
- Steric hindrance
- Reaction parameters(temperature)
- Torsional strain
- Electronic effects
- Leaving groups
Are E2 reactions are stereoselective or stereospecific?
E2 reaction can be stereoselective or stereospecific. If only one β-hydrogen is available then these are stereospecific whereas when two β-hydrogens are available then these reactions are stereoselective reactions.
Is SN2 the stereoselective reaction?
No SN2 is a stereospecific reaction.
- Stereoselective compounds (ucla.edu)
- Organic stereochemistry experimental and computational method by Hua-Jie Zhu.
- 2nd edition of Organic Chemistry by Jonathan Clayden, Nick Greeves, and Stuart Warren.