Chapter 7: Stereochemistry

1
Stereoisomers: isomers that have the same atoms bonded to one another
(same constitution), but different 3-D orientation of the atoms in space.

Conformational stereoisomers: interconvert by rotation about a bond

staggered and eclipsed conformers
gauche and anti conformers
chair-chair conformers

Configurational stereoisomers: cant be interconverted

cis and trans isomers
E and Z isomers

Two new ones:

enantiomers: stereoisomers that are nonsuperimposable mirror images
diastereomers: stereoisomers that are not mirror images

2
I. Enantiomers
A. Chirality: handedness

H H
Chem 3D
Br F F Br
Cl Cl

nonsuperimposable mirror images

a pair of enantiomers (left- and right-handed isomers)
a chiral molecule (shows handedness)
has a stereogenic center or stereocenter
is dissymmetric

Any tetrahedral carbon with 4 different groups

attached to it is a stereogenic carbon.

3
I. Enantiomers

Question 7-1. Indicate whether the following molecules have one or

more stereogenic carbons (carbons bonded to four different groups)
and label each stereogenic center. Click on the arrow to check your
answers.

OH H Br
F F

Cl
F

Check Answer

4
I. Enantiomers

Answer 7-1. The stereogenic carbons are indicated here.

OH H Br
* F F

* *
Cl
F

1 stereogenic no stereogenic 2 stereogenic no stereogenic

carbon carbon carbons carbon

5
I. Enantiomers
A. Chirality: handedness

H H
Chem 3D
H F F H
Cl Cl

superimposable mirror images (same!)

an achiral molecule
is symmetric (contains a plane of symmetry)

6
I. Enantiomers
A. Chirality: handedness
Question 7-2. Identify the stereogenic carbons in the following compounds,
and draw the two enantiomers. Click on the arrow key to check your answer.

Cl

Br

OH

Check Answer

7
I. Enantiomers
A. Chirality: handedness
Answer 7-2. The stereogenic carbons are indicated with an *.

*
H H Cl
Cl Cl

Br Br H H Br

OH H OH HO H

8
I. Enantiomers
B. Optical activity
The physical properties of enantiomers are identical (m.p., b.p., n, d, , etc.)
except the direction in which they rotate plane polarized light.
Enantiomers are optical isomers.

sample

polarizer

plane- dextrorotatory levorotatory optically

polarized (d) or (+) (l) or () inactive

optically active
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I. Enantiomers
B. Optical activity

Optically inactive: achiral molecule

or racemic mixture
- 50/50 mixture of two enantiomers

Optically pure: 100% of one enantiomer

Optical purity (enantiomeric excess)

= percent of one enantiomer percent of the other

e.g., 80% one enantiomer and 20% of the other

= 60% e.e. or optical purity

10
I. Enantiomers
B. Optical activity

Specific rotation:
temperature
observed rotation ()

[]TD =
cl path length (dm)

sodium D line concentration (g/mL soln)

e.g., (+)-2-butanol [] 27 = + 13.5

D
()-2-butanol 13.5

11
I. Enantiomers
C. Absolute configurations: R and S

Designate the configuration of atoms at a stereocenter.

H H
C OH HO C CH CH
CH3CH2 2 3
CH3 H3C

We can designate which is which by assigning an absolute configuration

to each of these (R or S) by a set of rules, but which is (+) and which is ()?

Answer: () (+) but,

There is no relationship between a molecules absolute configuration

and its optical rotation (its relative configuration).

12
I. Enantiomers
C. Absolute configurations: R and S
1. Assign priorities to the four groups according to the Sequence Rules.
2. Orient the molecule so that the lowest priority group points away
from you.
3. Determine the direction of procession of the other three groups, from
highest to lowest:
clockwise = R (rectus)
counterclockwise = S (sinister)

H CH3
C OH (R)-2-butanol
CH3CH2 Et OH
CH3
Chem 3D
H OH
C CH (S)-2-butanol
CH3CH2 3
Et CH3
OH
13
I. Enantiomers
C. Absolute configurations: R and S

Question 7-3. Name the following compounds, including R or S designation.

CH2Br
C H
CH3CH2
CH3

H CH3

Check Answer

14
I. Enantiomers
C. Absolute configurations: R and S

Answer 7-3. Name the following compounds, including R or S designation.

1
CH2Br (S)-1-bromo-2-methylbutane
2C H4
CH3CH2
CH3
3

3
4
H CH3
2 1
(R)-3-methylcyclohexene

15
I. Enantiomers
D. Fischer projections
A A A
D B = D B = C C
D
C C B

Determining R and S in Fischer projections:

H (R)-2-butanol
CH3 OH -when lowest priority group is on a vertical
CH2CH3 bond (back): read normally
CH3
(S)-2-butanol
H OH
-when lowest priority group is on a horizontal
CH2CH3 bond (forward): read backward
16
I. Enantiomers
D. Fischer projections
Manipulating Fischer projections:

CH3 CH2OH
rotate 180
H OH in plane HO H
(S) CH OH (S)
2 CH3

flip rotate
over
90
H
CH2OH CH3
HOCH2 CH3
H OH or HO H (R) OH
(R) CH (R) CH OH
3 2
17
I. Enantiomers
D. Fischer projections
Question 7-4. Assign R and S configurations. Then determine whether the
structures in each of the following pairs are enantiomers or identical.

CH3 H CH O CH O
H Br Br CH3 H OH HO H
CH2CH3 CH2CH3 CH2OH CH2OH

CO2- CH3 CH3 H

+ + H OH CH3CH2 CH3
H3N H H3N H
CH3 CO2- CH2CH3 OH
Check Answer

18
 I. Enantiomers
D. Fischer projections
Answer 7-4. Assign R and S configurations. Then determine whether the
structures in each of the following pairs are enantiomers or identical.
3 2
CH3 H CH O CH O
1 4 1
4
H Br Br CH3 H OH HO H
2 CH2CH3 CH2CH3 3 CH2OH CH2OH
S S identical R S enantiomers

2 3
CO2 - CH3 CH3 H
1 4 4 1
+ + H OH CH3CH2 CH3
H3N H H3N H
CH3 CO2- CH2CH3 OH
3 2

S R enantiomers S R enantiomers
19
I. Enantiomers
E. Reactions that create a chiral center
Rule: Optically inactive starting material can give only optically
inactive products

Br2
+ Br
h
Br achiral
chiral, but
racemic mixture
Br
Br2 C H
CH3CH2
Br H CH3
CH3CH2 C
CH3 H
CH3CH2
C CH3
Br2
sp2, planar Br
20mixture
50/50
I. Enantiomers
E. Reactions that create a chiral center
H2O
racemic
H2SO4
OH
OH
OH2
C H
+ H CH3CH2
CH3
H+
CH3CH2 C
CH3 H
CH3CH2
C CH3
OH2
sp2, planar OH

mCPBA CH3CH2 O
H + CH3CH2
O H
21
I. Enantiomers
E. Reactions that create a chiral center
Question 7-5. Draw the products of the following reactions, showing
stereochemistry where relevant.

Cl2
h

HBr

1) B2H6
2) H2O2, OH- Check Answer

22
I. Enantiomers
E. Reactions that create a chiral center
Answer 7-5. Draw the products of the following reactions, showing
stereochemistry where relevant.
Cl
Cl2 Cl
h Cl
Cl H H Cl

H Br Br H
Br
HBr

(rearrangement)

1) B2H6
2) H2O2, OH- HO H
H OH

23
II. Compounds Containing Two or More Chiral Centers
A. Diastereomers and enantiomers

Diastereomers: stereoisomers that are not mirror images

e.g. eclipsed and staggered

conformational diastereomers
anti and gauche
cis and trans configurational diastereomers

Diastereomers have different physical properties (i.e., can be separated).

n chiral carbons 2n possible stereoisomers

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II. Compounds Containing Two or More Chiral Centers
A. Diastereomers and enantiomers

e.g. CH3 CH CH CH3 22 = 4 possible stereoisomers

OH Br

CH3 CH3 CH3 CH3

H Br Br H H Br Br H
H OH HO H HO H H OH
CH3 CH3 CH3 CH3

enantiomers enantiomers

diastereomers
25
II. Compounds Containing Two or More Chiral Centers

Question 7-6. Draw all stereoisomers of 2-bromo-3-

chloropentane. Indicate R and S configurations of each
stereogenic center. Give the relationships between each pair of
stereoisomers.

Check Answer

26
II. Compounds Containing Two or More Chiral Centers

Answer 7-6. Be systematic. Draw one stereoisomer. Then draw

its mirror image. Then change one chiral center and draw its
mirror image.

CH3 CH3 CH3 CH3

S R R H S Br
H Br Br H Br H
H R Cl Cl S H H R Cl Cl S H

CH2CH3 CH2CH3 CH2CH3 CH2CH3

I II III IV

Enantiomers: I and II; III and IV

Diastereomers: I and III; I and IV, II and III; II and IV

27
II. Compounds Containing Two or More Chiral Centers
A. Diastereomers and enantiomers

Diastereomers: erythro and threo pairs of enantiomers

A A A A
C B B C C B B C
C' B' B' C' B' C' C' B'
A' A' A' A'

erythro diastereomer threo diastereomer

(name diastereomers on previous slide)

28
II. Compounds Containing Two or More Chiral Centers
A. Diastereomers and enantiomers

3 chiral carbons 23 = 8 possible stereoisomers

R, R, R : S, S, S
R, R, S : S, S, R
diastereomers
R, S, R : S, R, S
S, R, R : R, S, S

enantiomers

29
II. Compounds Containing Two or More Chiral Centers
B. Meso compounds: contain chiral carbons but are achiral

e.g. CH3 CH CH CH3 22 = 4 possible stereoisomers

Br Br

CH3 CH3 CH3 CH3

H Br Br H H Br Br H plane of
Br H H Br H Br Br H symmetry
CH3 CH3 CH3 CH3
threo erythro

enantiomers same! (superimposable)

meso compound

diastereomers
30
II. Compounds Containing Two or More Chiral Centers

Question 7-7. Draw all stereoisomers of 2,3-dibromohexane.

Indicate R and S configurations of each stereogenic center. Give
the relationships between each pair of stereoisomers.

Check Answer

31
II. Compounds Containing Two or More Chiral Centers

Answer 7-7. Since III has a plane of symmetry, so is meso, there

are only three stereoisomers. (The mirror image of III would not
an enantiomer, but would be identical to III.)

CH2CH3 CH2CH3 CH2CH3

R H S Br H S Br
Br H
R S R plane of symmetry;
H Br Br H H Br meso
CH2CH3 CH2CH3 CH2CH3

I II III

Enantiomers: I and II
Diastereomers: I and III; II and III

32
II. Compounds Containing Two or More Chiral Centers
C. Stereoisomers in substituted cyclohexanes

Cl Cl Cl
Cl Cl
achiral
(plane of symmetry)

Cl Cl

Cl Cl
but: chiral, enantiomers
CH3 H3C

33
II. Compounds Containing Two or More Chiral Centers
Question 7-7. Indicate whether each of the following cyclic
structures would be chiral or achiral. If a compound is chiral, give
the R or S configuration. If a compound is achiral, explain why.

Br Br Br
HO OH
Br Br

Br Br
Cl Cl

Check Answer

34
II. Compounds Containing Two or More Chiral Centers
Answer 7-7. Look for stereogenic carbons and planes of symmetry.
Remember that a plane of symmetry can dissect an atom or a bond.

Br Br Br
R HO OH
R Br R S Br
R S
S R
Br Br
Cl Cl

achiral: chiral achiral: no achiral: achiral:

meso stereogenic meso meso
carbon

35
II. Compounds Containing Two or More Chiral Centers
C. Stereoisomers in substituted cyclohexanes
Cl
Cl Cl
Cl Cl
Cl

Cl Cl

Cl Cl

Cl Cl Cl

Cl Cl Cl

Cl

Cl 36
II. Compounds Containing Two or More Chiral Centers
Question 7-8. Determine whether each of the following pairs of structures
represent identical compounds, enantiomers, or diastereomers.
CH3 Cl Cl
HO Br
H OH
H3C CH3 CH3
H Br
H H
CH3 H3C

CO2H CO 2H
CH3
H OH H OH
OH OH
H OH HO H
H3C
CH2OH CH2OH

CH3 CH3
O O
OH OH H CH3 H3C H
H3C H H CH3
Br Br Check Answer

37
II. Compounds Containing Two or More Chiral Centers
Answer 7-8. Determine whether each of the following pairs of structures
represent identical compounds, enantiomers, or diastereomers.
CH3 Cl Cl
HO Br
H OH
H3C CH3 CH3
H Br
H H
CH3 H3C
enantiomers
enantiomers
CO2H CO 2H
CH3
H OH H OH
OH OH
H OH HO H
H3C
CH2OH CH2OH
diastereomers
diastereomers
CH3 CH3
O O
OH OH H CH3 H3C H
H3C H H CH3
Br Br
enantiomers
enantiomers
38
 II. Compounds Containing Two or More Chiral Centers
D. Reactions that produce diastereomers

Br H CH3CH2 Br
Br2 CH3 + H C C
CH3CH2 C C H
CCl4
H Br Br CH3
racemic mixture
diastereomers

Br CH3 CH3CH2 Br
but " C C H H C C
CH3CH2 + CH3
"
H Br Br H
racemic mixture

stereospecific reaction: different stereoisomeric starting materials give

different stereoiosmeric products
39
II. Compounds Containing Two or More Chiral Centers
D. Reactions that produce diastereomers

O O
mCPBA H CH3 H3C H
+
H3C H H CH3
racemic

O
H H
"
H3C CH3
meso

40
II. Compounds Containing Two or More Chiral Centers
D. Reactions that produce diastereomers

H H H
CH3 CH3 CH3
H2
+
Pt
CH2 CH3 H
H CH3
optically active 68% 32%

Generation of a new chiral center in a chiral molecule does not

necessarily produce equal amounts of the two diastereomers.

41
II. Compounds Containing Two or More Chiral Centers
D. Reactions that produce diastereomers
Question 7-10. Draw the products of the following reactions, showing all
stereoisomers. If more than one stereoisomer is formed, give the relationship.
Br2

H2O

Br2

CCl4

H CH3
CH3CO2OH

H CH3 Check Answer

H2, Pd

42
II. Compounds Containing Two or More Chiral Centers
D. Reactions that produce diastereomers
Answer 7-10. The products are shown here. The relationship between the
stereoisomers is given.
OH CH3
Br2
CH3 OH enantiomers
H2O Br H
H Br

Br H
Br2
meso
CCl4
Br H

H CH3 H CH3 H CH3

CH3CO2OH
O O
diastereomers

H CH3 H CH3
H2, Pd
achiral (no chiral center)
43
III. Resolution of Enantiomers
separation of the two enantiomers

Enantiomers: identical physical properties; cant be separated

Diastereomers: different m.p., b.p., solubility, etc.
-can be separated by distillation, recrystallization, chromatography, etc.
Scheme:
A + B A B + A B diastereomers
racemic (R) (R,R) (S,R)
mixture single separate
of R & S enantiomer
(resolving
agent) A B A B
(R,R) (S,R)
remove B
A A
(R) (S)
44
III. Resolution of Enantiomers
O
H2N
OH +
Cl
racemic (S)

O O

O-H3N+ OH
Cl (R,S) H Cl (R)
1) separate
+ 2) HCl O
O

- + OH
O H3N
Cl H (S)
Cl (S,S)
45