1. Stereoisomerism
and Chirality
Unit 6

2. Isomers Isomers: different compounds with the same molecular formula
Constitutional isomers: isomers with a different connectivity
Stereoisomers: isomers with the same connectivity but a different orientation of their atoms in space

3. Enantiomers & Diastereomers
Stereoisomers can be subdivided into two general categories:
enantiomers & diasteromers
Enantiomers – stereoisomers whose molecules are nonsuperposable mirror images of each other
Diastereomers – stereoisomers whose molecules are not mirror images of each other

4. Chirality Chiral: from the Greek, cheir, hand
an object that is not superposable on its mirror image
Achiral: an object that lacks chirality; one that lacks handedness
an achiral object has at least one element of symmetry
plane of symmetry: an imaginary plane passing through an object dividing it so that one half is the mirror image of the other half
center of symmetry: a point so situated that identical components are located on opposite sides and equidistant from that point along the axis passing through it

5. Chirality & Stereochemistry
An object is achiral (not chiral) if the object and its mirror image are identical

6. Chirality
A chiral object is one that cannot be superposed on its mirror image

7. Elements of Symmetry
Symmetry in objects

8. Elements of Symmetry
Plane of symmetry (cont’d)

9. The Biological Significance of Chirality
Chiral molecules are molecules that cannot be superimposable with their mirror images
One enantiomer causes birth defects, the other cures morning sickness

10. The Biological Significance of Chirality
One enantiomer is a bronchodilator, the other inhibits platelet aggregation

11. The Biological Significance of Chirality
66% of all drugs in development are chiral, 51% are being studied as a single enantiomer
Of the $475 billion in world-wide sales of formulated pharmaceutical products in 2008, $205 billion was attributable to single enantiomer drugs

12. Chiral Center
The most common (but not the only) cause of chirality in organic molecules is a tetrahedral atom, most commonly carbon, bonded to four different groups
A carbon with four different groups bonded to it is called a chiral center
all chiral centers are stereocenters, but not all stereocenters are chiral centers
Enantiomers: stereoisomers that are nonsuperposable mirror images
refers to the relationship between pairs of objects
Enantiomers occur only with compounds whose molecules are chiral

13. Enantiomers 2-Butanol has one chiral center
here are four different representations for one enantiomer
using (4) as a model, here are two different representations for the enantiomer of (4)

14. Enantiomers The enantiomers of lactic acid
drawn in two different representations

15. Enantiomers
2-Chlorobutane

16. Enantiomers
3-Chlorocyclohexene

17. Enantiomers
A nitrogen chiral center

18. Geometrical isomers (cis & trans isomers) are:
Diastereomers

19. R,S Convention for naming Enantiomers
Priority rules
1. Each atom bonded to the chiral center is assigned a priority based on atomic number; the higher the atomic number, the higher the priority
2. If priority cannot be assigned per the atoms bonded to the chiral center, look to the next set of atoms; priority is assigned at the first point of difference

20. R,S Convention
3. Atoms participating in a double or triple bond are considered to be bonded to an equivalent number of similar atoms by single bonds

21. Naming Chiral Centers
1. Locate the chiral center, identify its four substituents, and assign priority from 1 (highest) to 4 (lowest) to each substituent
2. Orient the molecule so that the group of lowest priority (4) is directed away from you
3. Read the three groups projecting toward you in order from highest (1) to lowest priority (3)
4. If the groups are read clockwise, the configuration is R; if they are read counterclockwise, the configuration is S
(S)-2-Chlorobutane

22. Naming Chiral Centers
(R)-3-Chlorocyclohexene
(R)-Mevalonic acid

23. Enantiomers & Diastereomers
For a molecule with 1 chiral center, 21 = 2 stereoisomers are possible
For a molecule with 2 chiral centers, a maximum of 22 = 4 stereoisomers are possible
For a molecule with n chiral centers, a maximum of 2n stereoisomers are possible

24. Enantiomers & Diastereomers
2,3,4-Trihydroxybutanal
two chiral centers
22 = 4 stereoisomers exist; two pairs of enantiomers
Diastereomers:
stereoisomers that are not mirror images
refers to the relationship among two or more objects

25. Enantiomers & Diastereomers
2,3-Dihydroxybutanedioic acid (tartaric acid)
two chiral centers; 2n = 4, but only three stereoisomers exist
Meso compound: an achiral compound possessing two or more chiral centers that also has chiral isomers

26. Enantiomers & Diastereomers
2-Methylcyclopentanol

27. Enantiomers & Diastereomers
1,2-Cyclopentanediol O H H O O H H O H H H H
cis-
1,2-Cyclopentanediol
(a meso compound)
diastereomers O H H H H O H H O O H H
trans-
1,2-Cyclopentanediol
(a pair of enantiomers)

28. Enantiomers & Diastereomers
cis-3-Methylcyclohexanol

29. Enantiomers & Diastereomers
trans-3-Methylcyclohexanol

30. Isomers

31. Properties of Stereoisomers
Enantiomers have identical physical and chemical properties in achiral environments
Diastereomers are different compounds and have different physical and chemical properties
meso tartaric acid, for example, has different physical and chemical properties from its enantiomers