Stereoselectivity - Definition, Significance and Examples

In this article we will learn about stereoselectivity. Here we will discuss significance of stereoselective reactions with examples.  

Key words : Stereoselective Reaction, Isomers, Reaction Mechanism.

A stereoselective reaction is the one in which a reactant produces unequal mixture of isomers of expected product. In a stereoselective reaction, one isomer forms predominantly over other isomer. 

Table of Contents

1. Introduction
2. Characteristics of Stereoselective Reactions
3. Stereoselectivity in Elimination Reactions
4. Stereoselectivity in Addition Reactions
5. Significance of Stereoselective Reactions
6. Conclusion

1. Introduction

In a chemical reaction the isomer which is formed in more quantity is referred as "major isomer / product" however the isomer with less quantity is known as "minor  isomer / product". Therefore, it is said that stereoselectivity is property of chemical reaction in which single starting material gives unequal mixture of isomers.  

Figure 1 : Stereoselective Reaction

We have discussed  types of isomers of organic compounds in previous article. Please read for more details. [Link]

The main reason of stereoselectivity is difference in steric and electronic effects in mechanistic pathways to produce final product.

The stereoselective reactions can be observed in following types of reaction categories.

1. Elimination Reactions [Link]
2. Addition Reactions [Link]

We have studied these types of reactions in earlier articles. Please read for more details. 

2. Characteristics of Stereoselective Reactions

1. Stereoselective reactions gives mixture of products due to difference in steric and electronic effects in mechanistic pathways
2. Possibility of two or more products / isomers.
3. One isomer will be preferentially forms more than the other isomer.

3. Stereoselectivity in Elimination Reactions

There are two main types of elimination reactions found in organic chemistry

namely; E1 Elimination and E2 Elimination reaction.

Firstly, we will see stereoselectivity in E1 Reactions.

Consider the reaction of 1-bromo-1-methylcyclohexane with water in heating condition. This reaction provides unequal mixture of alkene products. This is also known as dehydrohalogenation of alkyl halide. In this reaction mechanism, step -1 is formation of carbocation. From the mechanism it is understood that there is a possibility of loss of H from two different sites (i.e. CH2 and CH3). (Fig 2)

Possibility 1: Loss of H from CH2 gives thermodynamically more stable and highly substituted alkene product.

Possibility 2: Loss of H from CH3 gives thermodynamically less stable highly strained alkene product.

Hence, due to stereoselectivity more stable and highly substituted alkene forms as major product. 

Figure 2: Stereoselectivity in E1 Elimination Reaction

Consider another example; 

Reaction of (2-bromopropyl)benzene with sodium ethoxide provides elimination product.

According to the mechanism there are two possibilities;

Possibility 1: Formation of stable trans alkene.

Possibility 2: Formation of less stable cis alkene.

The Newman projection formula of two respective conformers of alkyl halide shows that in one conformer Ph and CH3 close to each other (Dihedral angle is less). Hence this conformer is less stable and provides cis alkene which is also less stable.

However in other conformer consists of Ph and CH3 apart from each other (Dihedral angle is more). Therefore this conformer is more stable and provides trans alkene product.

Figure 3: Stereoselective Dehydrohalogenation

4. Stereoselectivity in Addition Reactions

Addition reactions such as epoxidation of alkenes shows stereoselectivity in the final product.

For example; epoxidation of bicyclo[2.2.2]oct-2-ene by using meta-Chloro peroxybenzoic acid (mCPBA) gives predominantly one isomer. 

Here there are two possibilities of peroxy-acid attack;

Possibility 1: Attack of peroxy-acid from less hindered side.

Possibility 2: Attack of peroxy-acid from more hindered side.

In this reaction attack of peroxy-acid is favored from less hindered side which eventually results in one major isomer and small amount of other isomer. 

Figure 4 : Stereoselective epoxidation of Alkene

We have studied nomenclature of bicyclic alkane compounds in previous article. Please read for more details. [Link]

Similarly reactions of epoxides with nucleophilic reagent such as Grignard reagents [Link] provides unequal mixture of compounds. 

Consider following example, a reaction of epoxide with phenyl magnesium bromide gives a product which is forms due to attack of Grignard reagent from less hindered side.

Figure 4: Addition of Grignard Reagent on Epoxide

5. Significance of Stereoselective Reactions

In organic chemistry for the synthesis of target molecules such as natural products or their analogues or any other designed molecules, organic chemists use multiple reactions as tool for the synthesis. In this context we need specific isomer of the compounds for target molecules. Therefore stereoselective reactions are helpful for targeted synthesis. Here we have discussed few very basic stereoselective reactions, but there are many other stereoselective reactions available in organic chemistry. we discuss various types of stereoselective reaction in upcoming articles. 

6. Conclusion

In this article we have discussed following points;

• A stereoselective reaction is the chemical reaction where one isomer of product forms preferentially over other isomer. 
• The main reason of stereoselectivity is difference in steric and electronic effects in mechanistic pathways to produce final product.
• Stereoselective reactions are helpful for targeted synthesis of organic compounds.

That's all for this topic, see you in next blog with another concept.