1. Chapter 15 Principles of Stereochemistry
Chapter 15 Principles of Stereochemistry ***Bring Your Model Kits to Class!***

3. Stereoisomers: compounds that have the same connectivity, but a different arrangement of atoms in space
Enantiomers: molecules that are non-superimposable (non-congruent) mirror images

4. Enantiomers

5. Carvone

6. Problem
Draw the missing enantiomer:

7. Enantiomers are said to be “chiral”
They possess the property of “chirality”
Greek: “hand” or “handedness”
No plane of symmetry

8. If a molecule is superimposable on its mirror image it is said to be “achiral”
Has a plane of symmetry

9. Chiral Carbons
Many chiral molecules contain one or more asymmetric carbons
Called “Chiral Carbons”
Attached to four different groups
Denoted by an asterisk
Source of stereoisomerism
Interchange of groups = other stereoisomer
Stereocenters

10. Problems
Identify, with an asterisk, the chiral carbons in the following molecules:

11. How do we differentiate between these two enantiomers
How do we differentiate between these two enantiomers? What do we call them?

12. Nomenclature of Enantiomers
Identify your chiral carbon
Prioritize your substituents on the chiral carbon according to the Cahn-Ingold-Prelog priority rules
Highest priority = 1, Lowest Priority = 4
Priority assignment rules:
Higher atomic # = higher priority
Higher isotopic mass = higher priority

13. If the first atoms connected to the chiral carbon are the same, continue moving outward until the first point of difference

14. Multiple-bonded atoms are equivalent to the same number of single bonded atoms

15. Point the lowest priority substituent away from you and look at the 3 remaining groups in a plane
Count  1, 2, 3
If you go CW = R
(rectus, Latin “proper”)
If you go CCW = S
(sinister, Latin “left”)

16. Name your enantiomers by placing an “(R)-” or an “(S)-” in front of the molecule’s IUPAC name

17. Problems Identify whether the following molecules are R or S.
Identify and name the following molecules:

18. For pharmaceuticals, slight differences in 3D spatial arrangement can make the difference between targeted treatment and undesired side effects. WHY?

21. Physical Properties of Enantiomers
Enantiomers share identical physical properties
m.p., b.p., nD, density, heats of formation etc.
Example: Lactic Acid
m.p. = 53°C
b.p. = 122°C
Lactic Acid

22. Enantiomers rotate a plane of polarized light in equal, but opposite directions
Called “Optical Activity”
Use Polarimeter

24. Optical Activity
If the sample rotates the plane of polarized light CW → dextrorotatory (+)
Latin: Dexter = Right
If the sample rotates the plane of polarized light CCW → levorotatory (-)
Latin = Laevus = Left
If one enantiomer is +, the other will be –
(+)-lactic acid (–)-lactic acid

25. The sign of optical rotation is unrelated to R and S configuration of a compound
(S)-(+)-lactic acid (R)-(–)-lactic acid

26. Optical rotation (a) is a quantitative measure of optical activity
[a] = a/cl
[a] = specific rotation
a = Observed rotation (degrees)
c = concentration (g/mL)
l = path length (dm)
Often, temp and wavelength indicated

27. (S)-(-)-glyceraldehyde [α]20 = -13.5° mL g-1 dm-1
(R)-(+)-glyceraldehyde
[α]20 = +13.5° mL g-1 dm-1

28. Racemic Mixtures
Racemic mixture/Racemate: a mixture containing equal amounts of two enantiomers
typically have different physical properties from that of the pure enantiomers
Example: Lactic Acid
m.p. (R or S) = 53°C
m.p. (R and S)= 17°C
Indicating racemic mixture:
Racemic Lactic Acid
(±)-Lactic Acid
Optical rotation = 0

29. Celexa vs. Lexapro Celexa = racemic mixture Lexapro = enantiopure S
R-(−)-citalopram
S-(+)-citalopram
Celexa = racemic mixture
Lexapro = enantiopure S
escitalopram

30. Fischer Projections
Convenient 2D representation of 3D carbohydrate molecules
Carbon chain written vertically
All bonds depicted horizontally and vertically
Chiral carbons are represented by crossing lines

31. Vertical bonds go back
Horizontal bonds come forward

32. Fischer Projections – More Complex
Based on an eclipsed molecular conformation

33. An interchange of any two of the groups bound to an asymmetric carbon changes the configuration of that carbon

34. Problems
Draw the enantiomer for the following molecule. Then, draw it as a molecular representation with dashes and wedges. Which is R? Which is S?
How many chirality centers does the following molecule possess? Draw L-Glucose.

35. Isomer Identification Flowchart

36. 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

37. Diastereomers and Enantiomers

38. Fischer Projections can also be used to quickly assess stereoisomeric relationships

39. Problem
Which of the following molecules are enantiomers? Which are diastereomers?