1. 9. Stereochemistry

2. A Brief Review of Isomerism
1. Constitutional Isomers or Structural Isomers: Have the same molecular formula but different connectivities among the constituent atoms. Therefore the functional groups can be different
2. Stereoisomers: Have the same molecular formula, the same connectivities among the constituent atoms but different spatial arrangements of atoms
Enantiomers: Pairs of stereoisomers that are non-superimposable mirror images of each other.
b. Diastereomers: Stereoisomers that are not mirror images of each other
i. Geometric Isomers: Cis-trans isomers; E-Z isomers
ii. Configurational Diastereomers

3. Examples of Structural Isomers:
Examples of Geometric Diastereomers:

4. Examples of Enantiomers & Configurational Diastereomers

5. Examples of Enantiomers
Molecules that have one carbon with 4 different substituents have a nonsuperimposable mirror image – enantiomer
Enantiomers do not have a plane of symmetry
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

6. Mirror-image Forms of Lactic Acid
When H and OH substituents match up, COOH and CH3 don’t
when COOH and CH3 coincide, H and OH don’t
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

7. The Reason for Enantiomerism : Chirality
Molecules that are not superimposable with their mirror images are said to be chiral
A plane of symmetry divides an entire molecule into two pieces that are exact mirror images
A molecule with a plane of symmetry is the same as its mirror image and is said to be achiral
The Flask has a plane of symmetry; It is achiral
The Palm has no Plane of symmetry; it is Chiral
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

8. McMurry Organic Chemistry 6th edition Ch 9 (c) 2003
Chirality Centers
A tetrahedral C in a molecule to which four different groups (or atoms) are attached is called a chirality center
There are two nonsuperimposable ways that 4 different groups (or atoms) can be attached to one carbon atom
A chiral molecule has at least one chirality center
When a molecule has more than 1 chirality center, it may be overall achiral or chiral depending on whether it has a plane of symmetry or not.
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

9. Chirality Centers in Chiral Molecules
Groups are considered “different” if there is any structural variation
In cyclic molecules, we compare by following in each direction in a ring
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

10. McMurry Organic Chemistry 6th edition Ch 9 (c) 2003
9.3 Optical Activity
Light restricted to pass through a plane is plane-polarized
Plane-polarized light that passes through solutions of achiral compounds remains in that plane
Solutions of chiral compounds rotate plane-polarized light and the molecules are said to be optically active
Phenomenon discovered by Biot in the early 19th century
Enantiomers rotate plane polarized light by the same magnitude but in opposite directions.
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

11. McMurry Organic Chemistry 6th edition Ch 9 (c) 2003
Optical Activity
Light passes through a plane polarizer
Plane polarized light is rotated in solutions of optically active compounds
Measured with polarimeter
Rotation, in degrees, is []
Clockwise rotation is called dextrorotatory
Anti-clockwise is levorotatory
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

12. Measurement of Optical Rotation
A polarimeter measures the rotation of plane-polarized that has passed through a solution
The source passes through a polarizer and then is detected at a second polarizer
The angle between the entrance and exit planes is the optical rotation.
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

13. McMurry Organic Chemistry 6th edition Ch 9 (c) 2003
Specific Rotation
To have a basis for comparison, define specific rotation, []D for an optically active compound
[]D = observed rotation/(pathlength x concentration) = /(l x C) = degrees/(dm x g/mL)
Specific rotation is that observed for 1 g/mL in solution in cell with a 10 cm path using light from sodium metal vapor (589 nanometers)
See Table 9.1 for examples
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

14. McMurry Organic Chemistry 6th edition Ch 9 (c) 2003
7.00 mg sample dissolved in 1.00ml solvent and solution was placed in a cell with 2.00 cm pathlength, an observed rotation of o was found. Calculate [ ]D for sample.
Answer:
C= g/1.00 mL =
[ ]D = /(l x C) = degrees/(dm x g/mL) = 0.08/(0.200× ) = 57.1 o
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

15. Specific Rotation and Molecules
Characteristic property of a compound that is optically active – the compound must be chiral
The specific rotation of the enantiomer is equal in magnitude but opposite in sign
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

16. Sequence Rules for Specification of Configuration
The configuration at a chirality center specifies the relative positions of the 4 groups attached to that center with respect to each other.
The 4 groups are ranked in priority from 1 to 4 using the Chan-Ingold-Prelog rules
Depending on the relative positions one of two labels, R or S, is applied.
With the lowest priority group (4) pointing away, the relative positions of the three other groups are compared.
If 1  2  3 follows a clockwise path, the configuration is specified R
If 1  2  3 follows an anti-clockwise path, the configuration is specified S
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

17. R-Configuration at Chirality Center
Lowest priority group is pointed away and direction of higher 3 is clockwise, or right turn
Note: If in the drawing the lowest priority group is not pointing away as required and the direction of the higher 3 is clockwise, then the configuration is S not R
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

18. Examples of Applying Sequence Rules
If lowest priority is back, clockwise is R and counterclockwise is S
R = Rectus
S = Sinister
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

19. 9.6 Diastereomers
In a molecule with multiple chiral centers, the mirror image is obtained when the positions of a pair of substituents is swapped FOR EVERY CHIRAL CENTER in the molecule
2R,3S
2S,3R
2R,3R
2S,3S
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
See Figure 9-10

20. McMurry Organic Chemistry 6th edition Ch 9 (c) 2003
9.7 Meso Compounds
Tartaric acid has two chirality centers and two diastereomeric forms
One form is chiral and the other is achiral, but both have two chirality centers
An achiral compound with chirality centers is called a meso compound – it has a plane of symmetry
The two structures on the right in the figure are identical so the compound (2R, 3S) is achiral
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

21. 9.8 Molecules with More Than Two Chirality Centers
Molecules can have very many chirality centers
Each point has two possible permanent arrangements (R or S), generating two possible stereoisomers
So the number of possible stereoisomers with n chirality centers is 2n
Cholesterol has eight chirality centers
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

22. For example, we worked 1,2-dimethylcyclobutane in class.
There are 2 chiral centers.
Therefore the maximum number of stereoisomers (enantiomer & diasteromer) = 22 = 4.
Trans-1,2-dimethylcyclobutane is chiral.
There are 2 enantiomers of the trans-1,2-dimethylcyclobutane: (1R,2R)-1,2-dimethylcyclobutane & (1S,2S)-1,2-dimethylcyclobutane.
Cis-1,2-dimethylcyclobutane is a meso compound & therefore achiral.
The two possible mirror images, namely, (1R,2S)-1,2-dimethylcyclobutane & (1S,2R)-1,2-dimethylcyclobutane are identical.
So if we have a formula with n chiral centers, of the maximum of 2n isomers, some may be identical if they achiral. You can only figure it what are meso or not meso by drawing the structures.

23. 9.9 Physical Properties of Stereoisomers
Enantiomeric molecules differ in the direction in which they rotate plane polarized but their other common physical properties are the same
Diastereomers have a complete set of different common physical properties
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

24. 9.10 Racemic Mixtures and Their Resolution
A 50:50 mixture of two chiral compounds that are mirror images does not rotate light – called a racemic mixture or racemate
The pure compounds need to be separated ot resolved from the mixture
To separate components of a racemate, we make a derivative of each with a chiral substance that is free of its enantiomer (resolving agent)
This gives diastereomers that are separated by their differing solubility
The resolving agent is then removed
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

25. 9.12 Stereochemistry of Reactions: Addition of HBr to Alkenes
Many reactions can produce new chirality centers from compounds without them
What is the stereochemistry of the chiral product?
What relative amounts of stereoisomers form?
Example addition of HBr to 1-butene
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

26. Achiral Intermediate Gives Racemic Product
Addition via carbocation
Top and bottom are equally accessible
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

27. 9.13 Stereochemistry of Reactions: Addition of Br2 to Alkenes
Stereospecific
Forms racemic mixture
Bromonium ion leads to trans addition
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

28. Addition of Bromine to Trans 2-Butene
Gives meso product (both are the same)
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

29. McMurry Organic Chemistry 6th edition Ch 9 (c) 2003
If your starting material is an achiral alkene (no chiral C’s present), then halogenation or hydrohalogenation will result in a racemic mixture of enantiomeric products.
The net rotation due to a racemic mixture = 0
If your starting material is a chiral alkene, for example, with 1 chiral C, then the product will be a mixtures of diastereomers. This is illustrated on the next slide.
The net rotation due to a mixture of diastereomers is not 0.
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

30. 9.14 Stereochemistry of Reactions: Addition of HBr to a Chiral Alkene
Gives diastereomers in unequal amounts.
Facial approaches are different in energy
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

31. McMurry Organic Chemistry 6th edition Ch 9 (c) 2003
9.17 Prochirality
A molecule that is achiral but that can become chiral by a single alteration is a prochiral molecule
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

32. Prochiral distinctions: faces
Planar faces that can become tetrahedral are different from the top or bottom
A center at the planar face at a carbon atom is designated re if the three groups in priority sequence are clockwise, and si if they are counterclockwise
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003

33. Prochiral distinctions, paired atoms or groups
An sp3 carbon with two groups that are the same is a prochirality center
The two identical groups are distinguished by considering either and seeing if it was increased in priority in comparison with the other
If the center becomes R the group is pro-R and pro-S if the center becomes S
McMurry Organic Chemistry 6th edition Ch 9 (c) 2003