Nomenclature of Organic Compounds
Bonding in Organic Chemistry
Radical Reactions
Acid-Base Chemistry
Alcohols, Ethers, Epoxides, Thiols, Sulfides, Amines
Alkenes and Alkynes
Conjugated Systems
Aromatic Compounds
Aldehydes and Ketones
Carboxylic Acids and Carboxylic Acid Derivatives
Enols and Enolates
Integrated Topics

R/S Stereodescriptors for Heteroatoms

Can we only assign the R/S stereodescriptors to carbons? No! Other atoms can have the stereodescriptors as well! In the previous tutorial we talked about the basic rules of how we assign the R and S stereodescriptors to simple molecules. Here, I want to talk about those cases when instead of a carbon atom we have a heteroatom such as S, N, P, etc.

Let’s look at this molecule here:

In this molecule we have a nitrogen atom (N) connected to four different groups. And, if an atom is attached to four different groups, it is chiral. Thus, we can assign a corresponding stereodescriptor to it. Notice, that a formal charge or any counter ions that might be present are completely irrelevant for our analysis. We will only consider what is actually bound to nitrogen.

Doing a layer-by-layer analysis the way we’ve learned in the last tutorial, we can easily assign priorities to our groups.

As the lowest priority group is facing away from us, we can assign the stereodescriptor right the way. In this case, it is the “S” isomer.

What if we have an electron pair?

Most heteroatoms contain non-bonding electron pairs. Due to the quantum channeling through the atom, the electron pair can flip-flop thus making any conversation about the stereochemistry of such atoms useless. However, this is not always the case. We can have molecules where the “flip” is difficult due to some steric restraints.

For instance, in the molecules above, we have a bulky tert-butyl group which makes it unfavorable for the ethyl group on the nitrogen to stay on the same side of the molecule where the t-butyl group is. By having both substituents in an equatorial position, the molecule achieves the lowest energy, and thus, highest stability.

As the electron pair is sitting on the sp3-hybridized orbital, it is directional. For the simplicity of the representation, we can put the electron pair on a “bond” as if it is a substituent of its own.

Now, we can assign our priorities. The electron pair has the lowest possible priority. This means that it is even lower in priority than a hydrogen atom.

This way, when we assign our priorities, we can proceed as usual with our stereodescriptor assignments.

Beware of the implicit electron pairs!

Here’s something important: in organic chemistry we often omit the electron pairs when we draw our structures. However, just because we didn’t show them, doesn’t mean they are no longer there! So, always check for the implicit electron pairs in the molecule before doing any kind of stereochemical analysis. For instance:

In this molecule we have sulfur seemingly connected to only three groups. This is in actuality is not correct because there’s an implicit electron pair on the sulfur atom. And as the oxygen atom is oriented away from the observer, it means that the electron pair must be looking at us. This brings additional complication because we no longer have the lowest priority group conveniently pointing away from us.

After assigning the priorities like we would normally do remembering to give the electron pair the lowest priority, we can then use the “double-flip” method to reorient the molecule in space. By doing so, we can easily assign the stereodescriptor to our molecule. This molecule is an “R” isomer.