Stereochemistry

Chirality

We can tell if an object has chirality by examining the object and its mirror image.

Many objects are achiral. By this we mean that the object and its mirror image are identical—that is, the
object and its mirror image are superposable one on the other.

Superposable means that one can, in one’s mind’s eye, place one object on the other so that all parts of
each coincide.

A chiral object is one that cannot be superposed on its mirror image.

Isomerism

Isomers are different compounds that have the same molecular formula.

Constitutional Isomers

Constitutional isomers have the same molecular formula but different connectivity (different
constitution), meaning that their atoms are connected in a different order.

Example:
Stereoisomers

Stereoisomers have their atoms connected in the same sequence (the same constitution), but they differ
in the arrangement of their atoms in space.

Stereoisomers can be subdivided into two general categories: those that are enantiomers of each other,
and those that are diastereomers of each other.

Enantiomers are stereoisomers whose molecules are non-superposable mirror images of each other.

All other stereoisomers are diastereomers.

Diastereomers are stereoisomers whose molecules are not mirror images of each other.

Enantiomers

Enantiomers – Two stereoisomers, each a non-superimposable mirror images of the other.

Example:

Louis Pasteur discovered that sodium ammonium salts of tartaric acid crystallize into right-handed and
left-handed forms. The optical rotations of equal concentrations of these forms have opposite optical
rotations. The solutions contain mirror image isomers, called enantiomers and they crystallized in
distinctly different shapes – such an event is rare.
The IUPAC sequence rules

The IUPAC (International Union of Pure and Applied Chemistry) sequence rules, also known as the priority
rules, or the Cahn Ingold-Prelog scheme, are a set of guidelines used to determine the priority of
functional groups in a molecule. These rules are used in naming organic compounds.

R.S Cahn, C. Ingold and V. Prelog devised a system to allow us to indicate the stereochemistry of
enantiomers (isomeric compounds that are mirror images of each other).

Note: Stereochemistry- chemistry of stereoisomers, i.e. a compound which has the same constitution and
bonding of atoms but which differs in their spatial arrangement.

The rules are as follows:

I. Atoms with higher atomic numbers are given higher priority. For example, oxygen (atomic number
8) has higher priority than carbon (atomic number 6).

II. In case of ties, the priority is determined by the atomic number of the next atoms along the chain
until a difference is found. For example, if two functional groups are both attached to carbon, the
priority is determined by the atomic number of the atoms attached to the carbon.

III. Double and triple bonds are treated as if they were single bonds to identical atoms, and as if they
were equivalent to two or three single bonds to the same atom(s).

With the lowest priority group pointing away, look at remaining 3 groups in a plane.

• Clockwise is designated R.

• Counterclockwise is designated S.
Diastereomers

Molecules with more than one chirality center have mirror image stereoisomers that are enantiomers.

In addition, they can have stereoisomeric forms that are not mirror images, called diastereomers.
Fischer Projection

Fischer projection is a way to represent the three-dimensional structure of a chiral molecule on a two-
dimensional plane. It is commonly used to determine the configuration of chiral centers in organic
molecules.

Here are the steps to use Fischer projection to determine the configuration of a chiral center:

1. Draw a vertical line to represent the longest carbon chain of the molecule, with the chiral center
in the middle of the line.
2. Place the substituent with the lowest priority (usually hydrogen) at the bottom of the vertical line.
3. Assign priorities to the other three substituents on the chiral center according to the Cahn-Ingold-
Prelog rules. The higher the atomic number of the atom attached to the chiral center, the higher
the priority.
4. Rotate the molecule so that the group with the lowest priority (usually hydrogen) is pointing away
from you (on the vertical lines).
5. Determine the configuration of the chiral center based on the arrangement of the substituents
on the Fischer projection. If the highest priority substituent is on the right side, the chiral center
has an R configuration (from the Latin "rectus", meaning right). If the highest priority substituent
is on the left side, the chiral center has an S configuration (from the Latin "sinister", meaning left).

The following video help explain how to use R S Configuration & Fischer Projections:

https://www.youtube.com/watch?v=yzfcrwJ37kI
Meso Compounds

Isomers which contain two or more stereocentres but which are superimposable with its mirror image.

An achiral compound with chirality centers is called a meso compound – it has a plane of symmetry.
Alkene

Cis-trans isomerism is a type of stereoisomerism in which two or more compounds have the same
molecular formula and sequence of bonded atoms, but differ in the arrangement of their atoms in space
due to the presence of a rigid double bond or a ring structure.

The E and Z nomenclature is based on the Cahn-Ingold-Prelog priority rules, which assign a priority to the
substituent groups attached to the two carbons of the double bond. The rule states that the group with
the highest atomic number has the highest priority, and if there is a tie, the next atoms in the substituent
groups are compared until a difference is found.

If the two highest-priority groups are on the same side of the double bond, the compound is designated
as Z (from the German zusammen, meaning "together"). If they are on opposite sides of the double bond,
the compound is designated as E (from the German entgegen, meaning "opposite").
Newman Projection

A Newman projection is a way to visualize the conformational isomers of a molecule.

In a Newman projection, a molecule is viewed along a carbon-carbon bond, with one carbon atom in front
of the plane of the paper and the other carbon atom behind the plane of the paper. The viewer then looks
down the carbon-carbon bond axis and imagines the molecule as a set of sticks and balls, with the balls
representing atoms and the sticks representing bonds.

The Newman projection shows the relative orientation of the atoms or groups attached to the two
carbons of the bond. It allows us to visualize the different conformations of the molecule as it rotates
around the carbon-carbon bond. By rotating the molecule and looking at it from different angles, we can
see how the atoms move in three dimensions and how they interact with each other.

Staggered conformation: In a staggered conformation, the atoms or groups attached to the two carbon
atoms of the bond are as far apart from each other as possible. This creates a lower energy state for the
molecule and is therefore more stable than the eclipsed conformation. There are two types of staggered
conformations: anti and gauche.

I. In an anti-conformation, the largest groups attached to each carbon are as far apart from each
other as possible, which results in a dihedral angle of 180 degrees between them. This is the most
stable staggered conformation.
II. In a gauche conformation, the largest groups attached to each carbon are slightly closer to each
other, resulting in a dihedral angle of 60 degrees between them. This is less stable than the anti-
conformation but still more stable than the eclipsed conformation.
Eclipsed conformation: In an eclipsed conformation, the atoms or groups attached to the two carbon
atoms of the bond are directly in line with each other. This creates a higher energy state for the molecule
and is therefore less stable than the staggered conformation.
Energy diagram

As we can see from the diagram, the anti-conformation has the lowest energy level, as the largest groups
attached to each carbon atom are as far apart from each other as possible. The gauche conformation has
a slightly higher energy level, as the largest groups are closer to each other, resulting in some steric
hindrance between them.

The eclipsed conformation has the highest energy level of the two types of conformations, as the atoms
or groups attached to the two carbon atoms are directly in line with each other.