Stereocenters

Introduction to Stereochemistry

Stereochemistry is a specialized area within the field of chemistry that is concerned with the study and manipulation of the spatial arrangement of atoms within molecules. It is primarily focused on understanding the relationships between stereoisomers, which are molecules that have the same molecular formula and sequence of bonded atoms, but differ in the three-dimensional positioning of atoms.

Hash and Wedge Bond Basics

In line-angle drawings, straight lines represent bonds in the plane of the page, or in this case, your screen. Wedge bonds (solid, filled-in triangular bonds), represent bonds coming out of the page, toward you. Hashed bonds, the ones represented by a series of parallel lines, represent bonds going into the page, away from you. When only one hash or wedge is shown on a carbon atom, it is assumed that the opposite hash/wedge is a hydrogen atom, as shown below:

Stereocenters and R/S Descriptions

A stereocenter is a specific point within a molecule, often an atom like carbon, that serves as the focal point for stereoisomerism. The presence of stereocenters allows for the theoretical prediction of the number of possible stereoisomers using the formula 2^n, where 'n' represents the number of tetrahedral stereocenters. However, this calculation can be reduced by certain compounds, such as meso compounds, which exhibit symmetry that reduces the actual number of stereoisomers.

Chirality centers, a subset of stereocenters, are characterized by their four distinct substituent groups and the requirement for sp3 hybridization, which means they can only have single bonds. These centers are defined by the spatial arrangement of their four different ligands, which makes them non-superposable on their mirror images. While typically associated with carbon, chirality centers can also involve other elements such as phosphorus or sulfur.

The broader definition of a chirality center includes any atom with four unique attachment groups, where swapping any two groups results in an enantiomer. Consequently, all chirality centers qualify as stereocenters, but the converse is not always true. Stereocenters may possess either sp3 or sp2 hybridization and require a minimum of three attachments to form a new stereoisomer upon group interchange.

Stereocenters play a crucial role in identifying whether a molecule is chiral or achiral. A molecule devoid of stereocenters is deemed achiral, whereas the presence of one or more stereocenters indicates the potential for chirality. However, exceptions exist, such as meso compounds, which are achiral despite having multiple stereocenters due to their inherent internal plane of symmetry.

Summary:

sp3-hybridized carbon atoms that have 4 different things attached to them are called any of the following:
- stereocenters
- stereogenic centers
- chiral centers
- centres of chirality
Stereocenters are designated either “R” or “S”

Cahn-Ingold-Prelog Rules

Atoms or groups of atoms attached to an sp3-hybridized carbon, or a chiral carbon, are given designations based on atomic number only. Atomic masses are considered only when comparing different isotopes of the same atomThe higher the atomic number of the immediate substituent atom, the higher the priority.
If two substituents have the same immediate substituent atom, look at atoms progressively further away from the chiral carbon until a difference is found.
If double- or triple-bonded groups are encountered as substituents, they are treated as an equivalent set of single-bonded atoms.

Example:

In the above example, fluorine has an atomic number of 9, whereas the carbon atoms attached to the chiral carbon have atomic numbers of 6, and the hydrogen has an atomic number of 1. Thus, we assign fluorine priority 1. For priority 2, we look at the two carbon atoms attached. The methyl and ethyl groups both have carbon as the first atom attached to the chiral carbon, so we have to look at one atom over. The methyl group carbon has 3 hydrogen atoms attached and the ethyl group carbon has 1 carbon and 2 hydrogen atoms attached, meaning it will be a higher priority over the methyl group.
To determine the R/S configuration, place the lowest-priority group, the hydrogen atom, facing away from you, as shown below:

Draw arrows from 1 to 2 to 3, as shown below:

If the arrows turn clockwise, the stereocenter designation is “R”, if they turn counterclockwise, the designation is “S”

The lowest priority group is facing toward you instead of away from you, do the R/S designation using the same steps shown above, but at the end just write the letter opposite to that which you determined. For example, if you determined that the stereocenter is “R” using the above steps, but the lowest priority group is pointing toward you, just write “S”.