chapter 5

Chapter 5: Stereochemistry Recall: Constitutional Isomers are molecules with the same molecular formula (ie number of C, H, O, N etc) but different connectivity which could mean different substituent locations, different functional groups, etc. But what if there is another type of isomer? One that is even more specific? � Stereoisomer: Same molecular formula and same connectivity of atoms but different spatial (3D) arrangement of atoms. There are different types of molecules that fit under the term stereoisomers.

Cis, Trans Stereoisomers: Same connectivity, but not identical in three dimensional space.

With Alkenes: To maintain the necessary orbital overlap to have a pi bond, carbon carbon double bonds do not have free rotation. Because of this, the direction where bonds are placed off of alkene carbons results in molecules that are not identical. These are also stereoisomers.

Stereoisomers: Chirality Arguably the most important stereoisomers are those that are chiral. A chiral molecule is asymmetric meaning that it is not the same as its mirror image. We use the term non-superimposable to highlight that it is not the same as its mirror image. Essentially, this means that if you were to stack two molecules on top of one another, they wouldn’t properly stack. Why do we care?? Because sometimes even a difference in 3D orientation between two chiral molecules is enough to have drastic effects when used in areas like medications. Even our sense of smell is dependent on the chirality of molecule both the smell receptors in our nose and what we are smelling! chiral

Determining Chirality: A chiral center must be an sP3 hybridized tetrahedral carbon atom with four unique substituents attached.

Enantiomers: two molecules that are chiral that are non-superimposable mirror images. A molecule can only have one enantiomer no matter how many chiral carbons it has Ways to Represent Enantiomers: “You Can Change One But Not Both”. Since enantiomers are mirror images, we can represent them by drawing the other molecule as its mirror image (but leaving the wedge/dash bond the same) OR more commonly, we draw the molecule in the same orientation but you cannot do both! If you do, you are drawing the identical molecule. This will be proven when we learn how to name chiral centers.

Remember, enantiomers occur because the molecule is chiral! A molecule only has an enantiomer if it has chiral center(s). Naming Chiral Centers: R/S Configuration Enantiomers are different compounds, so they must have different names. Each chiral center is either labeled as “R” or “S”. Enantiomers always have opposite configurations at every chiral carbon.

Steps to Determine R/S Configuration: 1. Prioritize four different groups attached to the chiral carbon based on atomic number 2. Arrange molecule so lowest priority is away from you (on a dashed bond) 3. Determine the direction that the highest 3 groups are going R= clockwise S= counterclockwise

Alternatively, if you don’t have a model, there are a couple different options if you can’t physically rotate the lowest priority group to be away from you. You can perform a “single swap” where you swap the lowest priority group with another group. This makes the enantiomer, so you know your original molecule is the opposite

special properties of enantiomers

enantiomers have identical physical properties including boiling point, melting point, Rf values, density etc making them very difficult to separate from one another in lab

there are two properties that they don’t share with each other which are their interactions with other chiral compounds and their ability to rotate plane polarized light which we call optical activity

enantiomers will rotate light in equal amount of degrees but opposite directions. an instrument called a polarimeter is used to measure the degrees and direction that light is rotated. this is the molecules’s specific rotation

the negative sign indicated counterclockwise light rotation and the positive sign indicates clockwise light rotation. the direction of light roataion has no correlation to R/S configuration!

whena analyzing a pair of enantiomers together then one entatiomer must be present in a higher percentage than he other to see light rotation. if an equal amount of each enantiomer is present, the net light rotation is zero and the mixture is not optically active

the majority of the reactions that we will learn in this course cannot selectively form one enantiomer as the product over the other. we often get roughly 50:50 ration of both which is called racemic mixture.

sterochemistry relationships when more than one chiral center is present:

When a molecule has more than one chiral center, we introduce a new type of
stereoisomer besides just the enantiomer. The maximum number of stereoisomers
possible for a compound can be determined by 2^n where n= number of
stereoisomers

Note: this includes all stereoisomers not just chiral centers but cis/trans alkenes too!
Super Note: the key word here is possible. Sometimes the maximum number is not
possible, and we will see this when we discuss meso compounds

Here, 4 stereoisomers gives us two pairs of enantiomers. But what is the relationship
between the other molecules? 🤔
3 & 4 are diastereomers of 1 & 2 and vice versa.
diastereomers are stereoisomers that are not mirror images.

molecule can have many diastereomers but can only have enantiomer. This is because to make a diastereomer, you change the configuration at one or more but not all stereocenters.

Diastereomers have completely different physical properties and are easy to separate.
When Molecules with Chiral Centers Are Achiral: Meso Compounds
Meso compounds occur when a molecule with an even number of chiral centers
possess a plane of symmetry which makes it identical to its mirror image. Since
chirality is dependent on a “handedness” ie a difference in 3D orientation, meso
compounds are achiral and not different in 3D.
Helpful Tip: Meso compounds are super symmetrical in order to have a plane of
symmetry. This means all substituents attached to each chiral center have to be the
same.
plane of symmetry

How to Convert a Molecule Into a Fischer Projection:
A Fischer Projection is a 2D representation of molecules containing one or more•
chiral centers. It’s a very common way to represent carbohydrates! n a Fischer Projection you want your lowest priority group to be on a vertical bond if•
you need to assign R/S. If it’s not, you can single swap!

E/Z Assignments for Alkenes:
Necessary for Alkenes that have 3 or more substituents attached to the alkene•
where we can’t use “cis” and “trans” naming system.
E Alkene: Highest Priority Groups on opposite sides of the double bond derived•
from the German word “entgegen” for opposite
Z Alkene: Highest Priority Groups on same side of the double bond derived from the•
German word “zussamen” for opposite
Priority ranking for each carbon is determined the same way R/S is determined
atomic number.