1. Introduction to Organic Chemistry 2 ed William H. Brown

2. Chirality
Chapter 4

3. Stereoisomers
Have the same molecular formula and the same order of attachment of their atoms (the same connectivity), but different three-dimensional orientations of their atoms in space.
example: the cis-trans isomers of cycloalkanes

4. Stereoisomers
Are divided into enantiomers and diastereomers

5. Chirality
Chiral: objects that are not superposable on their mirror images are said to be chiral; that is, they show handedness
Achiral: objects that are superposable on their mirror images are said to be achiral; that is, they do not show handedness.
an object is achiral if it possesses a plane of symmetry

6. Plane of Symmetry
Plane of symmetry: an imaginary plane dividing an object such that one half is the mirror image of the other half

7. Plane of Symmetry

8. Chirality Lactic acid is chiral; that is
it and its mirror image are nonsuperposable
it and its mirror image are enantiomers

9. Stereocenter
The most common (but not the only ) cause of chirality in organic molecules is the presence of a stereocenter
Stereocenter: an atom in a molecule at which interchange of two atoms or groups of atoms bonded to it gives a stereoisomer
the most common type of stereocenter is a tetrahedral carbon atom with four different groups bonded to it.

10. Stereocenter
2-Chlorobutane has one stereocenter and exists as a pair of enantiomers

11. R,S - Priority Rules
Each atom bonded to the stereocenter is assigned a priority
1. Priority is based on atomic number; the higher the atomic number, the higher the priority

12. R,S - Priority Rules
2. If priority cannot be assigned on the basis of atoms bonded directly to the stereocenter, look to the next set of atoms and continue until priority is assigned

13. R,S - Priority Rules
3. Atoms participating in a double bond are considered to be bonded to an equivalent number of similar atoms by single bonds

14. R or S Configuration
1. Locate th stereocenter, identify its four substituent, and assign each a priority from 1 (highest) to 4 (lowest)
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 reading is clockwise, configuration is R (from the Latin rectus); if it is counterclockwise, configuration is S (from the Latin sinister)

15. R or S Configuration
(S)-2-Chlorobutane

16. R or S Configuration
(R)-3-Chlorocyclohexene

17. Two or More Stereocenters
For a molecule with n stereocenters, a maximum of 2n stereoisomers are possible
with 1 stereocenter, 21 = 2 stereoisomers are possible
with 2 stereocenters, a maximum of 22 = 4 stereoisomers are possible
etc.

18. Two or More Stereocenters
2,3,4-Trihydroxybutanal
two stereocenters; 22 = 4 stereoisomers exist

19. Two or More Stereocenters
2,3-Dihydroxybutanedioic acid (tartaric acid)
2n = 4, but only three stereoisomers exist
Meso compound: an achiral compound possessing two or more stereocenters

20. Two or More Stereocenters
2-Methylcyclopentanol

21. Two or More Stereocenters
1,2-Cyclopentanediol

22. Two or More Stereocenters
cis-3-Methylcyclohexanol

23. Two or More Stereocenters
trans-3-Methylcyclohexanol

24. 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 (see Table 4.1)

25. Plane Polarized Light
Ordinary light: consists of waves vibrating in all planes perpendicular to its direction of propagation
Plane polarized light: consists of waves vibrating only in parallel planes
Polarimeter: a device for measuring the extent of rotation of plane polarized light
Observed rotation: the number of degrees, a, through which a compound rotates the plane of polarized light
Dextrorotatory (+): rotation of the plane of polarized light to the right
Levorotatory (-): rotation of the plane of polarized light to the left

26. Optical Activity
Specific rotation: observed rotation of the plane of polarized light when a sample is placed in a tube 1.0 dm in length and at a concentration of 1 g/mL

27. Optical Activity
For a pair of enantiomers, the value of the specific rotation of each is the same, but opposite in sign

28. Resolution Racemic mixture: an equimolar mixture of two enantiomers
because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific activity is zero
Resolution: the separation of a racemic mixture into its enantiomers

29. Resolution
One means of resolution is to convert the pair of enantiomers into two diastereomers
diastereomers are different compounds and have different physical properties, which can be used to separate them
A common reaction for chemical resolution is salt formation
after separation of the diastereomers, the enantiomerically pure acids are recovered

30. Resolution
Examples of enantiomerically pure bases

31. Resolution
Naproxen resolved by way of its ethyl ester

32. Resolution

33. Chirality in the Biological World
Except for inorganic salts and a few low-molecular-weight organic substances, the molecules of living systems are chiral
Although these molecules can exist as a number of stereoisomers, generally only one is produced and used in a given biological system
It is a chiral world!

34. Chirality in the Biological World
Consider chymotrypsin, a protein-digesting enzyme in the digestive system of animals
chymotrypsin contains 251 stereocenters
the maximum number of stereoisomers possible is 2251
There are only 238 stars in our galaxy!

35. Chirality in the Biological World
Enzymes are like hands in a handshake
the substrate fits into a binding site on the enzyme surface
a left-handed molecule will only fit into a left-handed binding site and
a right-handed molecule will only fit into a right-handed binding site
enantiomers have different physiological properties because of the handedness of their interactions with other chiral molecules in living systems

36. Chiral Drugs
Some chiral drugs are sold as racemic mixtures, others as a single enantiomer

37. Chiral Drugs

38. Chirality
End of Chapter 4