1. Stereochemistry 1. Stereoisomerism 2. Chirality
Chapter 3
Stereochemistry
1. Stereoisomerism
2. Chirality
3. Naming stereocenters - R/S configuration
4. Acyclic Molecules with 2 or more stereocenters
5. Cyclic Molecules with 2 or more stereocenters
6. Properties of Stereocenters
7. Optical activity
8. Separation of Enantiomers, Resolution
9. Significance of Chirality in the biological world
Lect 6, Sept 17, 2002
Lecture 6, Feb 11, 2003
Lecture 7 Fall 03
February 6 04 20 a c b

2. enantiomers diastereomers ISOMERISM constitutional
same molecular formula, but different….
constitutional
connectivity
different
stereoisomers - same connectivity
different 3D orientation
configurational isomers
conformational isomers
chair/boat
Start of lecture 6, Sept
enantiomers
mirror images
non-superposable
diastereomers
non-mirror images
(cis/trans)

3. diastereomers
trans
cis

4. enantiomers
e.g. Prozac - one isomer (“S”) is significantly more active

5. Chirality - right and left-handed substances
- 2 spatial arrangements of atoms
- analyze reflections (mirrors)
same (achiral), different (chiral).
mirror
plane
chiral -non-superposable, different arrangements in space

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

7. If symmetry element is present,
Elements of Symmetry
Conformations of 2,3-butanediol*
syn - plane of symmetry
anti - point of symmetry . .
If symmetry element is present,
substance is achiral
*meso or R,S (later)

8. Elements of Symmetry
Center of symmetry: a point situated so identical components of the object are located equidistant on opposite sides.

9. Chirality superposable mirror images - same compound
rotate 180o
superposable mirror images
- same compound
- a plane of symmetry - achiral

10. mirror images,  enantiomers
Chirality-sp3 or tetrahedral center with 4 different
groups = chiral molecule
rotate e.g. (180o)
see if images are
superposable, e.g. Cl Cl Cl C F H Br C C H H F F Br Br
Different, non-superposable
mirror images,
 enantiomers

11. enantiomers Tetrahedral - 4 different substituents (sp3)Cl C F Br H
Stereocenter
Stereogenic center
- an atom that interchange of 2 groups gives a stereoisomer

12. Enantiomers R/S R S Lactic acid
How do we distinguish chiral molecules?
R S
R/S

13. R,S Convention Priority rules
Assign priority to each atom bonded to stereocenter.
higher atomic number
higher priority
Increasing priority
(7)
-NH2
(8)
-OH
(17)
-Cl
(35)
-Br
(1)
(6) -H
-CH3

14. R,S Convention “Z” stereocenter, 4 gps. O > N > C > H
2. If same atoms bonded to the stereocenter, look to next set of atoms.
Priority to the first point of difference.
“Z” stereocenter, 4 gps.
O > N > C > H
8 > 7 > 6 > 1

15. R/S absolute configuration of chiral compounds
Rules:
1. Identify stereogenic center (C - 4 different gps.)
2. Assign priority to groups (C - 1, 2, 3, 4)
3. View C with “4” back; 1, 2, 3 FRONT
4. If 1>2>3 clockwise = R; counterclockwise = S 3 C 2 1 4 R

16. R & S configuration
enantiomers R S

17. R,S Convention
3. Atoms in double (triple) bond viewed as equivalent number of single bonds
(C is a stereogenic center)
view as

18. S H^C priorities and assigning R/S 4 vs vs 1 H C H C 3 2 C H
End lecture 6, sept 13, 2001

19. Assign R/S to the stereogenic center of the ester
rotate 180o S

20. Assign R/S to stereogenic carbon in coniine
Assign R or S to carvone
S caraway/dill R
spearmint
Assign R/S to stereogenic carbon in coniine
Golden pitcher plant
R-(-)-coniine
poison hemlock

21. Enantiomers & Diastereomers
For a molecule with n stereocenters, a maximum of 2n stereoisomers “might” be possible.
For a molecule with 1 stereocenter, 21 = 2 stereoisomers are possible.
Start lecture 7, Sept 18, 2001
Start lecture 7, Sept 19, 2002
For a molecule with 2 stereocenters, a MAXIMUM of 22 = 4 stereoisomers might exist.

22. 2n
256 (ignore sugar)

23. earlier
R|S
what about a second center?
R - R
R - S
S - R
S - S S R

24. * * Molecules with more than 1 stereocenter 22 = 4
trans-1-bromo-2-chlorocyclopropane *
relative stereochemistry - both are ‘trans’
absolute stereochemistry - each is unique, enantiomers
End of 6, start of lecture 7 R S
(1R,2R)-1-bromo-2-chlorocyclopropane
(1S,2S)-1-bromo-2-chlorocyclopropane

25. * * diastereomers diastereomers diastereomers enantiomers enantiomers
Molecules with more than 1 stereocenter *
trans-1-bromo-2-chlorocyclopropane
22 = 4 *
cis-1-bromo-2-chlorocyclopropane
(1S,2R)-1-bromo-2-chlorocyclopropane
(1R,2S)-1-bromo-2-chlorocyclopropane
diastereomers
diastereomers
diastereomers R S
enantiomers
enantiomers R S
(1R,2R)-1-bromo-2-chlorocyclopropane
(1S,2S)-1-bromo-2-chlorocyclopropane

26. Molecules with more than 1 stereocenter
(1S,2R)-1-bromo-2-chlorocyclopropane
(1R,2S)-1-bromo-2-chlorocyclopropane R S R S
(1R,2R)-1-bromo-2-chlorocyclopropane
(1S,2S)-1-bromo-2-chlorocyclopropane

27. Molecules with more than 1 stereocenter
(1S,2R)-1-bromo-2-chlorocyclopropane
(1R,2S)-1-bromo-2-chlorocyclopropane R S R S
(1R,2R)-1-bromo-2-chlorocyclopropane
(1S,2S)-1-bromo-2-chlorocyclopropane

28. 2 or more stereocenters with symmetry leads
to a meso isomer, superposable mirror images.
Consider 2,3-dibromobutane: S S R R
Lecture 7 September 19, 2002 S R S R

29. meso isomer is diastereomeric to enantiomers
2 or more stereocenters with symmetry leads
to a meso isomer, superposable mirror images.
Consider 2,3-dibromobutane: S R S R
meso isomer is diastereomeric to enantiomers
meso isomer S R R S
only 3 realized
part2