This chapter discusses stereochemistry and chirality. It defines stereoisomers such as enantiomers, which are nonsuperimposable mirror images, and diastereomers, which are not mirror images. Chiral carbons have four different groups and exist as enantiomers. Enantiomers have identical properties except for how they interact with other chiral molecules and rotate plane-polarized light in opposite directions. Methods to determine chirality such as assigning R/S configurations and using Fischer projections are covered. The chapter also discusses resolving enantiomers through formation of diastereomers.

1. Chapter 5
Stereochemistry
Organic Chemistry

2. Chapter 5 2
Chirality
• “Handedness”: right glove doesn’t fit the
left hand.
• Mirror-image object is different from the
original object. =>

3. Chapter 5 3
Stereoisomers
• Geometric isomers: cis-trans isomers.
• Enantiomers: nonsuperimposable mirror
images, different molecules.
=>
cis-1,2-dichlorocyclopentane trans -1,2-dichlorocyclopentane
H
Cl
H
Cl
H
Cl
H
Cl
H
Cl
Cl
H
H
Cl
Cl
H

4. Chapter 5 4
Chiral Carbons
• Tetrahedral carbons with 4 different
attached groups are chiral.
• Its mirror image will be a different
compound (enantiomer). =>

5. Chapter 5 5
Mirror Planes of Symmetry
• If two groups are
the same, carbon
is achiral.
(animation)
• A molecule with an
internal mirror
plane cannot be
chiral.*
Caution! If there is no plane of symmetry,
molecule may be chiral or achiral. See if
mirror image can be superimposed. =>

6. Chapter 5 6
(R), (S) Nomenclature
• Different molecules (enantiomers) must
have different names.
• Usually only one enantiomer will be
biologically active.
• Configuration around the
chiral carbon is specified
with (R) and (S).
C
C
O OH
H3C
NH2
H
natural alanine
=>

7. Chapter 5 7
Cahn-Ingold-Prelog Rules
• Assign a priority number to each group
attached to the chiral carbon.
• Atom with highest atomic number
assigned the highest priority #1.
• In case of ties, look at the next atoms
along the chain.
• Double and triple bonds are treated like
bonds to duplicate atoms.
=>

8. Chapter 5 8
Assign Priorities
C
C
O OH
H3C
NH2
H
natural alanine
1
2
3 4
Cl
HCl
H
*
1
2
3
4
1
2
3
4
=>
C
C
O
H
C
H CH2
CH2OH
CH(CH3)2
* C
C
C
CH2OH
CH(CH3)2
H
O
O
C
C
H CH2
C
*
expands to

9. Chapter 5 9
Assign (R) or (S)
• Working in 3D, rotate molecule so that
lowest priority group is in back.
• Draw an arrow from highest to lowest
priority group.
• Clockwise = (R), Counterclockwise = (S)
=>

10. Chapter 5 10
Properties of Enantiomers
• Same boiling point, melting point, density
• Same refractive index
• Different direction of rotation in polarimeter
• Different interaction with other chiral
molecules
– Enzymes
– Taste buds, scent
=>

11. Chapter 5 11
Optical Activity
• Rotation of plane-polarized light
• Enantiomers rotate light in opposite directions,
but same number of degrees.
=>

12. Chapter 5 12
Polarimetry
• Use monochromatic light, usually sodium D
• Movable polarizing filter to measure angle
• Clockwise = dextrorotatory = d or (+)
• Counterclockwise = levorotatory = l or (-)
• Not related to (R) and (S)
=>

13. Chapter 5 13
Specific Rotation
Observed rotation depends on the length
of the cell and concentration, as well as
the strength of optical activity,
temperature, and wavelength of light.
[α] = α (observed)
c • l
c is concentration in g/mL
l is length of path in decimeters.
=>

14. Chapter 5 14
Calculate [α]D
• A 1.00-g sample is dissolved in 20.0 mL
ethanol. 5.00 mL of this solution is
placed in a 20.0-cm polarimeter tube at
25°C. The observed rotation is 1.25°
counterclockwise.
=>

15. Chapter 5 15
Biological Discrimination
=>

16. Chapter 5 16
Racemic Mixtures
• Equal quantities of d- and l- enantiomers.
• Notation: (d,l) or (±)
• No optical activity.
• The mixture may have different b.p. and m.p.
from the enantiomers!
=>

17. Chapter 5 17
Racemic Products
If optically inactive reagents combine to
form a chiral molecule, a racemic
mixture of enantiomers is formed.
=>

18. Chapter 5 18
Optical Purity
• Also called enantiomeric excess.
• Amount of pure enantiomer in excess of
the racemic mixture.
• If o.p. = 50%, then the observed
rotation will be only 50% of the rotation
of the pure enantiomer.
• Mixture composition would be 75-25.
=>

19. Chapter 5 19
Calculate % Composition
The specific rotation of (S)-2-iodobutane is
+15.90°. Determine the % composition of a
mixture of (R)- and (S)-2-iodobutane if the
specific rotation of the mixture is -3.18°.
=>

20. Chapter 5 20
Chirality of Conformers
• If equilibrium exists between two chiral
conformers, molecule is not chiral.
• Judge chirality by looking at the most
symmetrical conformer.
• Cyclohexane can be considered to be
planar, on average.
=>

21. Chapter 5 21
Mobile Conformers
H
Br
H
Br
H
Br
H
Br
Nonsuperimposable mirror images,
but equal energy and interconvertible.
BrBr
H H
Use planar
approximation.
=>

22. Chapter 5 22
Nonmobile Conformers
If the conformer is sterically hindered, it
may exist as enantiomers.
=>

23. Chapter 5 23
Allenes
• Chiral compounds with no chiral carbon
• Contains sp hybridized carbon with
adjacent double bonds: -C=C=C-
• End carbons must have different groups.
Allene is achiral.
=>

24. Chapter 5 24
Fischer Projections
• Flat drawing that represents a 3D molecule
• A chiral carbon is at the intersection of
horizontal and vertical lines.
• Horizontal lines are forward, out-of-plane.
• Vertical lines are behind the plane.

25. Chapter 5 25
Fischer Rules
• Carbon chain is on the vertical line.
• Highest oxidized carbon at top.
• Rotation of 180° in plane doesn’t
change molecule.
• Do not rotate 90°!
• Do not turn over out of plane! =>

26. Chapter 5 26
Fischer Mirror Images
• Easy to draw, easy to find enantiomers,
easy to find internal mirror planes.
• Examples:
CH3
H Cl
Cl H
CH3
CH3
Cl H
H Cl
CH3
CH3
H Cl
H Cl
CH3
=>

27. Chapter 5 27
Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so
assignment rules are backwards!
• Clockwise 1-2-3 is (S) and counterclockwise
1-2-3 is (R).
• Example:
CH3
H Cl
Cl H
CH3
(S)
(S) =>

28. Chapter 5 28
Diastereomers
• Stereoisomers that are not mirror images.
• Geometric isomers (cis-trans)
• Molecules with 2 or more chiral carbons.
=>

29. Chapter 5 29
Alkenes
Cis-trans isomers are not mirror images,
so these are diastereomers.
C C
H H
CH3H3C
cis-2-butene trans-2-butene
C C
H
H3C
CH3
H =>

30. Chapter 5 30
Ring Compounds
• Cis-trans isomers possible.
• May also have enantiomers.
• Example: trans-1,3-dimethylcylohexane
CH3
H
H
CH3
CH3
H
H
CH3
=>

31. Chapter 5 31
Two or More Chiral Carbons
• Enantiomer? Diastereomer? Meso? Assign
(R) or (S) to each chiral carbon.
• Enantiomers have opposite configurations at
each corresponding chiral carbon.
• Diastereomers have some matching, some
opposite configurations.
• Meso compounds have internal mirror plane.
• Maximum number is 2n
, where n = the number
of chiral carbons.
=>

32. Chapter 5 32
Examples
COOH
H OH
HO H
COOH
(2R,3R)-tartaric acid
COOH
COOH
HO H
H OH
(2S,3S)-tartaric acid
=>(2R,3S)-tartaric acid
COOH
COOH
H OH
H OH

33. Chapter 5 33
Fischer-Rosanoff Convention
• Before 1951, only relative configurations
could be known.
• Sugars and amino acids with same relative
configuration as (+)-glyceraldehyde were
assigned D and same as (-)-glyceraldehyde
were assigned L.
• With X-ray crystallography, now know
absolute configurations: D is (R) and L is (S).
• No relationship to dextro- or levorotatory.
=>

34. Chapter 5 34
D and L Assignments
CHO
H OH
CH2OH
D-(+)-glyceraldehyde
*
CHO
H OH
HO H
H OH
H OH
CH2OH
D-(+)-glucose
*
COOH
H2N H
CH2CH2COOH
L-(+)-glutamic acid
*
=>

35. Chapter 5 35
Properties of Diastereomers
• Diastereomers have different physical
properties: m.p., b.p.
• They can be separated easily.
• Enantiomers differ only in reaction with
other chiral molecules and the direction
in which polarized light is rotated.
• Enantiomers are difficult to separate.
=>

36. Chapter 5 36
Resolution of Enantiomers
React a racemic mixture with a chiral compound to
form diastereomers, which can be separated.
=>

37. Chapter 5 37
Chromatographic
Resolution of Enantiomers
=>

38. Chapter 5 38
End of Chapter 5