1. Stereochemistry Dr. Sheppard CHEM 2411 Spring 2015
Klein (2nd ed.) sections , 8.4

2. Stereochemistry
Branch of chemistry concerned with the spatial arrangement of atoms in molecules
Stereoisomers:
Same molecular formula
Same connectivity
Different 3D orientation (cannot be converted via bond rotation)
Previously:
Cis and trans
Now:
Stereochemistry at tetrahedral centers
Enantiomers, diastereomers
E and Z

3. Chirality “handedness” Has a mirror image that is nonsuperimposable
Example: hand
Example: sunglasses
Chiral or not?
Chiral or not?

4. Chirality
A molecular example:
Try this with your model kit

5. Achiral molecules Are superimposable on their mirror images
Contain a plane of symmetry
Cuts through the middle of the molecule so that one half reflects the other half
achiral
chiral

6. Enantiomers Chiral molecules form enantiomers
Nonsuperimposable mirror images
Result from tetrahedral C (sp3) with 4 different substituents
This C is called a chirality center (or stereocenter, or asymmetric center) and are often marked with *
Examples of stereocenters:

7. Enantiomers
Example:
(+) and (-)-lactic acid are a pair of enantiomers

8. Identify the chirality centers

9. Molecule
Stereocenter?
Plane of Symmetry?
Chrial?

10. Not all molecules with stereocenters are chiral!
Plane of Symmetry?
Chrial?
Not all molecules with stereocenters are chiral!

11. Enantiomer Similarities and Differences
Same molecular formula, connectivity
Different 3D arrangement
Same physical properties (mp, bp, solubility)
Same spectroscopic properties (IR, NMR, etc.)
Same reactivity, in general
Products will have different stereochemistry
Only one will react with an enzyme (like a hand fitting in a glove)
Different designations (R vs. S)
Different optical activity

12. Optical Activity Rotation of plane- polarized light
Seen in chiral molecules
a = observed rotation; measured by the polarimeter
One enantiomer rotates light to the left a degrees
Levorotatory (-)
The other rotates light to the right a degrees
Dextrorotatory (+)

13. Optical Rotation
Depends on polarimeter pathlength (l) and sample concentration (c)
Specific rotation [a]D is observed under standard conditions
l = nm
l = 1 dm (10 cm)
c = 1 g/cm3
(-)-Lactic acid has a [a]D of -3.82
(+)-Lactic acid has a [a]D of +3.82
What is [a]D of a 50:50 mixture of (-) and (+)-lactic acid?

14. R and S designations
Used to describe 3D configuration about a chirality center
Not related to direction of optical rotation (+) and (-)
To designate R and S need to assign priorities to each group bonded to the stereocenter
Cahn-Ingold-Prelog system

15. Priority Rules
Higher atomic number (of atom bonded to C*) = higher priority
-Br > -Cl > -OH > -NH2 > -CH3 > -H
If 2 of the same atom are bonded to C*, look at atomic number of the next set of atoms

16. Continue process until first point of difference
Some more examples:

17. Priority Rules
Atoms in double bonds count twice; atoms in triple bonds count three times

18. Which substituent has the higher priority?
-Br Cl
-CH2CH3 -CH(CH3)2
-CH=CH2 -CH2CH3
-CHO -CO2H
-CH2OH -CH2CH2OH

19. To designate R or S: Locate chirality center
Assign priority to the 4 groups (1 = highest; 4 = lowest)
Orient molecule so substituent 4 is point away from you (with model or on paper)
Read the other groups 1→2→3 (draw arrow on paper)
Groups read clockwise = R; counterclockwise = S

20. Example: 2-bromobutane

21. Example: 2-bromobutane

22. Rank the following groups in order of priority from highest (1) to lowest (4):
-NHC(O)CH3 -OCH3 -OH -F

23. Draw R and S stereoisomers for 2-hydroxypropanal:

24. R and S stereoisomers for 3-methylhexane:
Hints:
Switch any two groups to draw the enantiomer
When substituent 4 is forward, 1→2→3 clockwise is S

25. Classify these as chiral or achiral:

26. How many chirality centers?

27. Rotating a Tetrahedral Carbon
To rotate a carbon and not accidentally change the R/S designation, keep one substituent in the same place, and rotate the other three.
Make sure all three groups are rotating in the same direction
Do not switch two groups; this changes the R/S designation

28. Classify these molecules as R or S:

29. Determine whether the two structures in each pair represent constitutional isomers, enantiomers, or identical compounds.

30. Fischer Projections Another way of drawing tetrahedral carbons
Horizontal lines = out of page
Vertical lines = into page
Frequently used for chirality centers, especially if a molecule has more than one chiral center

31. What is the relationship between these two molecules?

32. Molecules With Multiple Stereocenters
Maximum # stereoisomers = 2n where n = # stereocenters
# Stereocenters
# Stereoisomers
Stereoisomers 1 2 R S 4
(R,R)
(S,S)
(R,S)
(S,R)

33. Example: 2,3-Pentanediol
Draw Fischer projections for the 4 stereoisomers
Carbon chain vertical, C1 at top

34. Relationships A and B are enantiomers C and D are enantiomers
A and C, A and D, B and C, B and D are diastereomers

35. Diastereomers Stereoisomers that are not mirror images of each other
Different physical properties
With tetrahedral carbons, require at least 2 stereocenters
Cis-trans stereoisomers are also diastereomers

36. Meso Compounds Maximum # stereoisomers = 2n where n = # stereocenters
The # stereoisomers will be less than 2n when there is a meso compound
Meso compound
An achiral compound which contains chirality centers
Not optically active
The chirality centers typically are identical (have the same 4 substituents) and reflect each other in a plane of symmetry
Example:

37. Another Example: 2,3-Butanediol
A = (2R,3R)-2,3-butanediol
B = (2S,3S)-2,3-butanediol
C = D = meso-2,3-butanediol
C and D are superimposable mirror images (the same molecule)
Relationship between enantiomers and meso?
Diastereomers

38. Racemic Mixtures aka Racemate, + pair, or d,l pair
50% mixture of two enantiomers
Not optically active
Separation of enantiomers is difficult
Separation methods:
React with chiral compound to convert to a pair of diastereomeric salts, which can be separated by distillation, crystallization, etc.
Separate on chiral column
Separate with enzyme

39. Applications of Stereochemistry
Stereochemistry of reactions
If a product has a stereocenter, is the stereochemistry all R, all S, or a mixture?
To understand details, need to look at mechanism (next)

40. Applications of Stereochemistry
Reactions with enzymes
Receptors/enzymes react with only one enantiomer (like a handshake)
Limonene
R = orange odor
S = pine odor
Ibuprofen
R = inactive
S = active
D-Decalactone
R = porcupine emits to alert predators
S = coconut

41. Thalidomide How many chirality centers? How many stereoisomers?
How was the drug administered?
What effect did this have on patients who used thalidomide?
Francisco Goya

42. Alkene Stereochemistry
Previously, cis-trans stereoisomers
Now, E,Z-designation of alkenes
Use E,Z instead of cis-trans when
More than two substituents on C=C
Heteroatoms on C=C
To assign E or Z:
Rank the two groups on each carbon of the C=C according to the Cahn-Ingold-Prelog priority rules
If the higher priority groups are on the same side of the C=C, the alkene has Z geometry
If the higher priority groups are on opposite sides of the C=C, the alkene has E geometry

43. E and Z Configurations

44. Classify these alkenes as E or Z:

45. Name these alkenes:

46. Isomerism Worksheet

47. Next…
Organic reactions