The Stereochemistry of Alkene Addition Reactions
In the previous post, we talked about the Markovnikov’s rule and learned that in the addition reaction of HX to an unsymmetrical alkene, the H adds to the carbon that already has the greater number of hydrogen atoms. Or, looking from the perspective of the X group, we can say that the X atom (or group) adds to the carbon that already has the greater number of carbon atoms:
This is the regiochemistry of the reaction as it shows why one regioisomer (constitutional isomer) is formed preferentially over the other one.
Sometimes the addition to the alkene results in a product with one or two stereogenic (chirality) centers. The resulting product can be a mixture of stereoisomers which can be enantiomers or diastereomers.
At this point, it might be a good idea to refresh the concepts of constitutional and stereoisomers by following the corresponding links above. Additionally, you want to check some practice problems identifying molecules as Enantiomers Diastereomers the Same or Constitutional.
Without going too far, let’s look at the product in the reaction we just talked about. It has a chirality center and therefore can exist as two enantiomers:
The question is which one forms in excess, or in other words what is the stereochemistry of this, and in general, for the electrophilic addition reactions of alkenes. And this what we will discuss in today’ post.
Addition Reactions that Form a Product with One Chirality Center
There are two possible scenarios for the starting alkene that we can have;
1) the starting material alkene has no chiral centers
2) there is a chiral center in the alkene.
Let’s start with the first option.
Addition to an alkene with no stereogenic center
For example, draw the major product(s) of the following reaction:
For the regiochemistry, we know that according to the Markovnikov’s rule, the Br will be added to the more substituted carbon:
Notice that the carbon where the Cl had added became a chiral center, therefore we need to address whether it has an R or S absolute configuration. And the answer is that it actually is a racemic mixture of R and S enantiomers.
This is explained by the fact that carbocations are sp2-hybridized, flat centers (we are talking about the positively charged carbon) and the nucleophilic attack occurs from both sides:
This attack happens in the same amounts and as a result, a racemic mixture of two enantiomers is obtained.
- To summarize, addition reactions of alkenes with no stereogenic center that form a product with one stereogenic center produce a racemic mixture of enantiomers.
Scenario 2 – Addition to an alkene with a stereogenic center
If the starting alkene contains a chirality center, and the addition to the double bond creates a new chirality center, then the products are diastereomers:
The asymmetric center in the starting material is not changed since it does not participate in the reaction. The new asymmetric center, however, is opposite for each product depending on the face on which the bromide had attacked the carbocation.
- Therefore, the products are a mixture of diastereomers. Similar to this, SN1 reactions can also produce diastereomers even though we usually say that they give a racemic mixture. You can check problems 3.5 and 3.6.
Addition Reactions that Form a Product with Two Chirality Centers
Let’s consider the reaction of 1,2-dimethylcyclohexene with HBr. The starting material does not have any asymmetric centers. However, it produces four stereoisomers in this reaction!
Let’s see how this happens and what the relationship is between these stereoisomers. The first step is, as usual, the protonation of the double bond, and what is important here is to remember/visualize that the H can add from both faces of the double bond:
Notice that because of the hydrogen addition from different faces, the new chirality center can be either R or S, and statistically it forms in a 50:50 ratio. There is no preference as to hydrogen adding from one side or the other side – no stereoselectivity.
Similar to this, once the carbocation is formed, the bromide ion attacks the positively charged, trigonal planar carbon from above or below. This variety of additions results in four stereoisomers as final products.
To summarize, the addition of HBr to 1,2-dimethylcyclohexene proceeds through the formation of two planar carbocation intermediates, allowing the bromide ion to attack from either face. This creates two new stereocenters – one at the carbon bearing Br and the other at the carbon bearing H – giving a total of four stereoisomers. These consist of two pairs of enantiomers, and each pair is related to the other as diastereomers.
There is no control on the stereochemistry of this reaction, and the proton, as well as the bromide (or any other substituent), adds from both sides in equal amounts. Therefore, the reaction is not stereoselective, i.e., none of the stereoisomers is formed preferentially. It is also not stereospecific, as the same products are obtained regardless of whether the cis or trans stereoisomers of the alkene are used.
- Therefore, when two stereogenic centers are formed in an addition reaction of alkenes, all the possible stereoisomers are formed, and the product is a mixture of enantiomers and diastereomers.
Syn and Anti Additions to Alkenes
Labeling the addition as “above” and “below” is neither scientific nor accurate because the direction depends on the viewer’s perspective. Instead, chemists use the terms syn (same) and anti (opposite) to describe the stereochemistry of additions to alkenes. When two groups add to the same side of the double bond, the reaction is called a syn addition. If the groups add to opposite sides of the double bond, it is called an anti-addition.
We have already discussed that hydrohalogenation of alkenes gives a mixture of syn and anti addition products, primarily because the reaction proceeds through an ionic mechanism. The first step forms a planar carbocation, and the second step occurs from either face, leading to a mixture of syn and anti addition products.
Let’s now discuss some examples where there is actual control over the stereochemistry of the addition reaction, allowing us to selectively obtain either syn or anti addition products.
Let’s start with syn addition.
Syn Addition Reactions to Alkenes
A representative example of a syn addition is the hydroboration-oxidation reaction. In this reaction, the hydrogen and boron add to the same face of the alkene in a concerted step, and after oxidation, the boron is replaced by an OH group. As a result, the H and OH groups end up on the same side of the former double bond.
Syn addition is also observed in the dihydroxylation of alkenes with reagents such as OsO4 or cold, dilute KMnO4. These are called syn dihydroxylation reactions of alkenes. In these reactions, two hydroxyl groups are added to the same side of the double bond, producing a vicinal diol with syn stereochemistry.
Another important example of a syn addition is the catalytic hydrogenation of alkenes. In the presence of a metal catalyst such as Pd, Pt, or Ni, both hydrogen atoms are delivered from the metal surface to the same face of the alkene. Therefore, catalytic hydrogenation is always a syn addition reaction.
Anti Addition Reactions to Alkenes
It is also possible to add the OH groups on the opposite faces of the double, which is anti-dihydroxylation. A good example of an anti-addition is the dihydroxylation reaction through epoxide formation. When an alkene is treated with a peroxyacid, an epoxide is formed first. Subsequent acid-catalyzed hydrolysis opens the epoxide by backside attack, causing the two OH groups to appear on opposite sides of the ring. The overall result is an anti-dihydroxylation of the alkene.
These, of course, are not the only examples of syn and anti-addition reactions to alkenes. In fact, each of the reactions discussed above deserves a separate article to cover the mechanism, regiochemistry, stereochemistry, and synthetic applications in greater detail. You can find them by clicking on the links; however, since the goal of this article is to provide an overview of the stereochemistry of alkene addition reactions, we have summarized the main ones where the stereochemistry is relevant. Read the posts to go over each reaction, and at the end, of course, there are also additional examples of syn and anti-additions in the list of practice problems below.
Can you please explain more about d? Can a molecule be diastereomers without a chiral center? Thank you.
We normally say that diastereomers have at least one chiral center where the R, S configuration is the same i.e. it is R, R or S, S, and all the others are inverted, or, all of them are the same except one that is inverted. In other words, it can have all the chiral centers inverted because that makes two molecules enantiomers, and if they are all the same, then it is the same compound.
This brings a common question of whether diastereomers always have chiral centers, or, are they always chiral.
And the answer is no, they do not necessarily have chiral centers. The best example of this is the cis and trans or E and Z isomerism.
Because the connectivity of atoms is the same and the arrangement is different, these are stereoisomers. Specifically, because they are not mirror images, we classify them as diastereomers. So, cis and trans isomers are diastereomers.
Going back to the absolute configuration, we can say that if the diastereomers are chiral, then the statement about the R and S configuration is correct. However, if they are not, then it is irrelevant to talk about the R and S configuration and chirality in general – they are achiral diastereomers.
Thank you for the detailed explanation! It really helps.
Very welcome.