1. 4.13 Disubstituted Cyclohexane
When multiple substituents are present, the positioning of the groups on the chair must be shown by using solid or dashed wedges or by showing the groups in either axial or equatorial positions
Convince yourself that all of the molecules above are identical. It may help to use a handheld model
Practice with SkillBuilder 4.12
Copyright 2012 John Wiley & Sons, Inc.

2. 4.13 Disubstituted Cyclohexane
Consider both chair conformations for the following molecule
Which is more stable? WHY?
Do the same analysis for the following molecule
Practice with SkillBuilder 4.13
Copyright 2012 John Wiley & Sons, Inc.

3. 4.14 Cis-Trans Isomerism
When naming a disubstituted cycloalkane, use the prefix cis when there are two groups on the same side of the ring
Use the prefix trans when two substituents are on opposite sides of a ring
Copyright 2012 John Wiley & Sons, Inc.

4. 4.14 Cis-Trans Isomerism
These two structures are NOT constitutional isomers. WHY?
They are stereoisomers. HOW?
Practice with conceptual checkpoints
Copyright 2012 John Wiley & Sons, Inc.

5. 4.15 Polycyclic Systems
There are many important structures that result when more than one ring is fused together
We already looked at bicycloalkanes. Here are a couple more
Camphor and Camphene are fragrant natural products isolated from evergreens
Copyright 2012 John Wiley & Sons, Inc.

6. 4.15 Polycyclic Systems
Decalin is formed by fusing two chairs together
Diamonds are formed by fusing many chairs together three dimensionally in all directions
Copyright 2012 John Wiley & Sons, Inc.

7. 4.15 Polycyclic Systems
There are many biologically important steroids, all of which involve fusing cycloalkanes as part of their structure
Copyright 2012 John Wiley & Sons, Inc.

8. Chapter 5: Stereochemistry
The three-dimensional structure of a molecule can greatly affect its physical and chemical properties. Can you give some examples?
Three dimensional structure is critical in biochemistry. HOW?
Copyright 2012 John Wiley & Sons, Inc.

9. Chapter 5: Stereochemistry
For pharmaceuticals, slight differences in 3D spatial arrangement can make the difference between targeted treatment and undesired side-effects. WHY?
Isomers that have the same connectivity between atoms but different 3D, spatial arrangement of their atoms are called STEREOisomers
Copyright 2012 John Wiley & Sons, Inc.

10. 5.1 Isomers
Isomers are NONidentical molecules that have the same formula
There are two classifications of isomers
Draw a pair of molecules that are constitutional isomers
Copyright 2012 John Wiley & Sons, Inc.

11. 5.1 Isomers
C-C bonds that are constrained in a cyclic structure can not freely rotate
Although the two molecules below have the same connectivity, they are NOT identical.
The naming system we have learned thus far would give them the same name, but they are NOT identical, so we need to learn additional nomenclature rules…to be continued
Copyright 2012 John Wiley & Sons, Inc.

12. 5.1 Isomers
To maintain orbital overlap in the pi bond, C=C double bonds can not freely rotate.
Although the two molecules below have the same connectivity, they are NOT identical
Copyright 2012 John Wiley & Sons, Inc.

13. 5.1 Isomers
Identify the following pairs as either constitutional isomers, stereoisomers, or identical. EXPLAIN
Copyright 2012 John Wiley & Sons, Inc.

14. 5.1 Isomers
With rings and with C=C double bonds, cis-trans notation is used to distinguish between stereoisomers
Cis – identical groups are positioned on the SAME side of a ring
Trans – identical groups are positioned on OPPOSITE sides of a ring
Copyright 2012 John Wiley & Sons, Inc.

15. 5.1 Isomers
Cis – identical groups are positioned on the SAME side of a C=C double bond
Trans – identical groups are positioned on OPPOSITE sides of a C=C double bond
Practice with SkillBuilder 5.1
Copyright 2012 John Wiley & Sons, Inc.

16. 5.1 Isomers
Identify the following as either cis, trans, or neither. EXPLAIN
Copyright 2012 John Wiley & Sons, Inc.

17. 5.2 Stereoisomers
Beyond cis-trans isomers, there are many other important stereoisomers
To identify such stereoisomers, we must be able to identify chiral molecules
A chiral object is NOT identical to its mirror image
You are a chiral object. Look in a mirror and raise your right hand. Your mirror image raises his or her left hand.
You can test whether two objects are identical by seeing if they are superimposable.
Can you be superimposed upon your mirror image?
Copyright 2012 John Wiley & Sons, Inc.

18. 5.2 Stereoisomers Some other chiral objects include gloves. HOW?
Think of some other examples of chiral everyday objects
Chirality is important in molecules.
If two molecules are mirror images, they will have many identical properties, but because they are not identical, their pharmacology may be very different
Visualizing mirror images of molecules and manipulating them in 3D space to see if they are superimposable can be VERY challenging
It is highly recommended that you use handheld models as visual aids until you get more experience
Copyright 2012 John Wiley & Sons, Inc.

19. 5.2 Stereoisomers
Chirality most often results when a carbon atom is bonded to 4 unique groups of atoms.
Make a handheld model to prove to yourself that they are NOT superimposable
Copyright 2012 John Wiley & Sons, Inc.

20. 5.2 Stereoisomers
When an atom such as carbon forms a tetrahedral center with 4 different groups attached to it, it is called a chirality center (aka stereocenter or stereogenic center)
Analyze the attachments for each chirality center below
Practice with SkillBuilder 5.2
Copyright 2012 John Wiley & Sons, Inc.

21. 5.2 Stereoisomers
Identify all of the chirality centers (if any) in the following molecules
Copyright 2012 John Wiley & Sons, Inc.

22. 5.2 Enantiomers
Some stereoisomers can also be classified as enantiomers
Enantiomers are TWO molecules that are MIRROR IMAGES but are NONidentical and NONsuperimposable
For the pair below, draw in the missing enantiomer
Make handheld models for both structures to verify that they are NONidentical mirror images
Practice with SkillBuilder 5.3
Copyright 2012 John Wiley & Sons, Inc.

23. 5.2 Enantiomers
What is the relationship between the two molecules below?
Given that the molecules are so similar, how is it possible that our noses can distinguish between them?
Copyright 2012 John Wiley & Sons, Inc.

24. 5.3 Designating Configurations
Enantiomers are NOT identical, so they must not have identical names
How would you name these molecules?
Their names must be different, so we use the Cahn-Ingold-Prelog system to designate each molecule as either R or S.
Copyright 2012 John Wiley & Sons, Inc.

25. 5.3 Designating Configurations
The Cahn, Ingold and Prelog system
Using atomic numbers, prioritize the 4 groups attached to the chirality center
Arrange the molecule in space so the lowest priority group faces away from you
Count the group priorities 1…2…3 to determine whether the order progresses in a clockwise or counterclockwise direction
Clockwise = R and Counterclockwise = S
A handheld model can be very helpful visual aid for this process
Copyright 2012 John Wiley & Sons, Inc.

26. 5.3 Designating Configurations
The Cahn, Ingold and Prelog system
Using atomic numbers, prioritize the 4 groups attached to the chirality center. The higher the atomic number, the higher the priority
Prioritize the groups on this molecule
Copyright 2012 John Wiley & Sons, Inc.

27. 5.3 Designating Configurations
The Cahn, Ingold and Prelog system
Arrange the molecule in space so the lowest priority group faces away from you
This is the step where it is most helpful to have a handheld model
Copyright 2012 John Wiley & Sons, Inc.

28. 5.3 Designating Configurations
Using atomic numbers, prioritize the 4 groups attached to the chirality center
Arrange the molecule in space so the lowest priority group faces away from you
Complete steps 1 and 2 for the following molecule
Copyright 2012 John Wiley & Sons, Inc.

29. 5.3 Designating Configurations
The Cahn, Ingold and Prelog system
Counting the other group priorities, 1…2…3, determine whether the order progresses in a clockwise or counterclockwise direction
Clockwise = R and Counterclockwise = S
Copyright 2012 John Wiley & Sons, Inc.

30. 5.3 Designating Configurations
Designate each chirality center below as either R or S.
Copyright 2012 John Wiley & Sons, Inc.

31. 5.3 Designating Configurations
When the groups attached to a chirality center are similar, it can be tricky to prioritize them
Analyze the atomic numbers one layer of atoms at a time
First layer
Second layer 1 4
Tie
Is this molecule R or S? 2 3
Copyright 2012 John Wiley & Sons, Inc.

32. 5.3 Designating Configurations
Analyze the atomic numbers one layer of atoms at a time
First layer
Second layer 4 1
The priority is based on the first point of difference, NOT the sum of the atomic numbers
Is this molecule R or S?
Tie 3 2
Copyright 2012 John Wiley & Sons, Inc.

33. 5.3 Designating Configurations
When prioritizing for the Cahn, Ingold and Prelog system, double bonds count as two single bonds
Determine R or S for the following molecule
Copyright 2012 John Wiley & Sons, Inc.

34. 5.3 Designating Configurations
Handheld molecular models can be very helpful when arranging the molecule in space so the lowest priority group faces away from you
Here are some other tricks that can use
Switching two groups on a chirality center will produce its opposite configuration
Copyright 2012 John Wiley & Sons, Inc.

35. 5.3 Designating Configurations
Switching two groups on a chirality center will produce its opposite configuration
You can use this trick to adjust a molecule so that the lowest priority group faces away from you
With the 4th priority group facing away, you can designate the configuration as R
Work backwards to show how the original structure’s configuration is also R
Copyright 2012 John Wiley & Sons, Inc.

36. 5.3 Designating Configurations
Practice with SkillBuilder 5.4
Copyright 2012 John Wiley & Sons, Inc.

37. 5.3 Designating Configurations
The R or S configuration is used in the IUPAC name for a molecule to distinguish it from its enantiomer
Copyright 2012 John Wiley & Sons, Inc.

38. Study Guide for sections 4.13-4.15, 5.1-5.3
DAY 10, Terms to know:
Sections , ,3-diaxial strain, cis, trans, stereoisomers, chiral, achiral, superimposable, chiral center or stereocenter, enantiomers, Cahn-Ingold-Prelog system
DAY 10, Specific outcomes and skills that may be tested on exam 2:
Sections ,
Be able to use the cis and trans terminology when naming cyclic alkanes.
Be able to explain the difference between constitutional isomers and stereoisomers and recognize examples of each.
Be able to use the cis and trans terminology when identifying stereoisomeric alkenes.
Be able to identify all chiral centers in a molecule.
Be able to identify a pair of molecules as either, identical, constitutional isomers, enantiomers, diastereomers, or no relationship.
Be able to use the Cahn-Ingold-Prelog system to identify every chiral center as either R or S.
Be able to use proper R or S notation in the naming of chiral molecules using the IUPAC system.
Klein, Organic Chemistry 2e

39. Practice Problems for sections 4.13-4.15, 5.1-5.3
Complete these problems outside of class until you are confident you have learned the SKILLS in this section outlined on the study guide and we will review some of them next class period
Klein, Organic Chemistry 2e

40. Prep for Day 11 Must Watch videos: Other helpful videos:
(optical activity)
(enantiomeric excess calculations)
(mesocompounds)
(bond energies and enthalpy)
Other helpful videos:
(more on stereoisomers)
(lectures 16 and 17)
Read sections , 6.1
Klein, Organic Chemistry 2e