Section 3 - Stereochemistry

Section 3 - Problems
Stereochemistry
3.1 For the following structures, determine the configuration at each chiral centre.
a) b) c) d)
3.2 Decide if each of the following pairs represent unrelated compounds, identical compounds,
constitutional isomers (structural isomers), enantiomers, or diastereomers.
H3 C CH3 H3C
CH3 &
a)
H3C & H3C CH3
b) CH3 CH3
CH3 CH3 CH3

& H3C
& &
c) d) e)
H3C Cl H3C Cl
H3C O
&
& H3C
f) CH3 O CH3 g) Cl CH3 H3C Cl
H H
Cl Cl Cl CH3
& &
Br Cl Cl Br
h) H3C CH3 H3C Cl i) F F
H H H H
& &
Br Cl Cl F Br H H F
j) F Br k) F Br
H H
& Cl H Cl F
Cl CH3 H3C Cl &
l) F F m) Br F Br H
Extra Problems and Solutions – Shirley Wacowich-Sgarbi PhD– Langara College - page 44
O O
H3C CH3 H3C CH3
O
& O
n)
3.3 Find the chiral centers, label them R or S and name the compound.
CH3 CH3 CH3
HO
H H3C
HO
H3C H
H CH3
a) HO b) H3C c) H3C
H3C CH3
H3C
H CH3
d)
3.4 For each of the following structures, give an example of: structural isomer, cis-trans isomer
(if applies), an enantiomer (if applies) and a rotamer.
a) b) c)
COOH
Br
d) e) f)
g) h)
i) j)
Br
3.5 The naturally occurring form of the amino acid cysteine has the S configuration at its chirality
center. On treatment with a mild oxidizing agent, two cysteines join to give cystine, a disulfide.
Assuming that the chirality center is not affected by the reaction, is cystine optically active?
NH 2 NH2 NH 2
2 HSCH2CHCO2H HO2CCHCH2S SCH2CHCO2H
Cysteine Cystine
3.6 Ribose, an essential part of ribonucleic acid (RNA), has the following structure:
H H H OH
CHO
HO
Ribose
HO H HO H
a) How many chirality centers does ribose have? Identify them.

b) How many stereoisomers of ribose are there?
c) Draw the structure of the enantiomer of ribose.
d) Draw the structure of a diastereomer of ribose.
3.7 On catalytic hydrogenation over a platinum catalyst, ribose is converted into ribitol. Is ribitol
optically active or inactive? Explain.
H H H OH
CH 2 OH
HO
Ribitol
HO H HO H
3.8 Draw all the possible stereoisomers of 1,2-cyclobutanedicarboxylic acid, and indicate the
interrelationships. Which if any, are optically active? Do the same for 1,3-cyclobutanedicarboxylic
acid.
3.9 Allenes are compounds with adjacent carbon-carbon double bonds. Many allenes are chiral,
even though they don't contain chirality centers. Mycomycin, for example, a naturally occurring
antibiotic isolated from the bacterium Nocardia acidophilus, is chiral and has [D]D = -130. Explain
why mycomycin is chiral. Making a molecular model should be helpful.
HC C C C CH C CH CH CH CH CH CH 2 CO 2H
Mycomycin
3.10 Long before chiral allenes were known, the resolution of 4-methylcyclohexylideneacetic acid
into two enantiomers had been carried out. Why is it chiral? What geometric similarity does it have
to allenes?
CO2 H
H
C
H3C
H 4-Methylcyclohexylideneacetic acid
3.11 Ketones react with acetylide ion to give alcohols. For example, the reaction of sodium
acetylide with 2-butanone yields 3-methyl-1-pentyn-3-ol:
O
H3C OH
1. Na+ - C CH
C C
H 3C CH 2CH3 2. H 3O + C CH 2CH3
HC
2-butanone 3-methyl-1-pentyn-3-ol
a) Is the product chiral? Is it optically active?
b) How many stereoisomers of the product are formed, what are their stereochemical
relationships, and what are their relative amounts?
c) In the laboratory, what separation method can be used to separate these stereoisomers?
3.12 Imagine that another reaction similar to problem 3.7 is carried out between sodium acetylide
and (R)-2-phenylpropanal to yield 4-phenyl-1-pentyn-3-ol:
H CH 3 H CH 3
C O 1. Na+ - C CH C
OH
C C
2. H3 O+
H C
H
CH
(R)-2-phenylpropanal 4-phenyl-1-pentyn-3-ol
a) Is the product chiral? Is it optically active?

b) How many stereoisomers of 4-phenyl-1-pentyn-3-ol are formed, and what are their
stereochemical relationships?
c) In the laboratory, what separation method can be used to separate these stereoisomers?
3.13 How is compound A related to compounds B-E? Choose from enantiomers, diastereomers,
constitutional isomers, or identical molecules.
B
C
NH2
NH2
A
E D
NH2
NH2
NH2
3.14 Artemisinin and mefloquine are widely used antimalarial drugs.
Artemisinin Mefloquine CF3

H
N CF3
O
O
O
H H H
H
O HO N
H H
O
a) Locate the stereogenic centers in both drugs.

b) Label each sterogenic center in mefloquine as R or S.
c) What is the maximum number of stereoisomers possible for artemisinin?
d) How are the N atoms in mefloquine hybridized?
e) Can two molecules of artemisinin intemolecularly hydrogen bond to each other?
f) What product is formed when mefloquine is treated with HCl? (Hint: use pKa table Klein 23.1)
3.15 For each structure,

i) Draw all the stereoisomers.
ii) Label each structure as chiral or achiral.
iii) Give the relationships between the stereoisomers (enantiomers, diastereomers).
3.16
a) Draw all the stereoisomers of 2,3,4-tribromopentane. You should find two meso structures
and one pair of enantiomers.
b) Star (*) the asymmetric carbon atoms, and label each as (R) or (S).
c) In the meso structures, show how C3 is not asymmetric, nor is it a chirality center, yet it is a
stereocenter.
d) In the enantiomers, show how C3 is not a stereocenter in this diastereomer.
3.17 A graduate student was studying enzymatic reductions of cyclohexanones when she
encountered some interesting chemistry. When she used an enzyme and NADPH to reduce the
following ketone, she was surprised to find that the product was optically active. She carefully
repurified the product so that no enzyme, NADPH, or other contaminants were present. Still, the
product was optically active.
COOH COOH
NADPH HO
O enzyme
H
H H
optically active?
a) Does the product have any asymmetric carbon atoms or other stereocenters?
b) Is the product capable of showing optical activity? If it is, explain how.
c) If this reaction could be accomplished using H2 and a nickel catalyst, would the product be
optically active? Explain.
3.18 D-(-)-Erythrose has the formula HOCH2 — CH(OH) — CH(OH) — CHO, and the D in its name
implies that it can be degraded to D-(+)-glyceraldehyde. The (-) in its name implies that D-(-)-
erythrose is optically active (levorotatory). When D-(-)-erythrose is reduced (using H2 and a nickel
catalyst), it gives an optically inactive product of formula HOCH2 — CH(OH) — CH(OH) — CH2OH.
Knowing the absolute configuration of D-(+)-glyceraldehyde, determine the absolute configuration
of D-(-)-erythrose. H OH
D-(+)-glyceraldehyde: HO
CHO
3.19 Label each pair of molecules below as: enantiomers; identical, structural isomers, cis-trans
isomers, configurational isomers or unrelated (not isomers). And determine whether a 50:50
mixture of the two are optically active of not.
a) b)
c) d)
Section 3 – Solutions
Stereochemistry
3.1 a) (2S, 3R)-3-Methyl-pentan-2-ol b) (3S, 4S)-2,4-Dimethyl-hexan-3-ol

H
H
H HO (S) (S)
(S)
(R) H
H OH
c) (2R, 3S)-3-Methyl-pentan-2-ol d) (S)-2-Ethyl-pentanoic acid

H O
H
(R) OH (S)
(S) OH
H H
H
3.2
a) unrelated compounds (not isomers) b) constitutional isomers
c) constitutional isomers d) identical compounds
e) constitutional isomers f) identical compounds
g) constitutional isomers h) diastereomers
i) enantiomers j) identical compounds
k) identical compounds l) enantiomers
m) diastereomers n) constitutional isomers
3.3
a) (R)-1,2-propanediol b) (S)-2,3-dimethyl-2-pentanol
c) (S)-3-methylhexane d) (S)-3,4,4-trimethyl-1-phenylheptane
3.4 Note: There are many correct answers for some of these!
Problem Structural isomer Cis-trans isomer Enantiomer Rotamer
(many answers (or diastereomer) (many answers

possible) possible)
a)
other answer exists
b)
COOH
other answer exists
c)
Not applicable Not applicable Not applicable
d) Diastereomer Cl
other answers exist
e) O
Not applicable
f)
Not applicable
g)
Not applicable
other answers exist
h) Diastereomer
other answers exist
i)
Br
j)
Not applicable
3.5
H H H H
S + S S S
C C C C
H2N CO2H H2N CO2H
CH2SH HSH2C CH2S SCH2
HO2C NH2 HO2C NH2
Cystine has the (S,S) configuration and is optically active since there is no plane of symmetry.
3.6
H H H OH H H HO H
CHO CHO
* * * * * *
HO HO
HO H HO H H OH H OH
ribose enantiomer of ribose
Ribose has 3 chirality centers, which give rise to 2(3) = 8 stereoisomers.
Ribose has 6 diastereomers:

H H H OH H H HO H
CHO CHO
HO * * * HO * * *
H OH HO H HO H H OH
H H HO H H H H OH
CHO CHO
HO * * * HO * * *
HO H HO H H OH H OH
H H H OH
H H HO H
CHO
HO * * * CHO
HO * * *
HO H H OH
H OH HO H
3.7 Ribitol is an optically inactive meso compound. Catalytic hydrogenation converts the aldehyde
functional group into a hydroxyl group and makes the two halves of ribitol mirror images of each
other.
plane of symmetry
H H H OH H H H OH
CHO H2 CH 2 OH
HO Pt catalyst HO
HO H HO H HO H HO H
ribose ribitol
3.8
CO 2H H H
H HO2C H
S S R R S R
HO2C H H HO2C
C B CO2H A CO2H
trans cis
meso
B and C are enantiomers and are optically active. Compound A is their diastereomer and is a meso
compound, which is not optically active.
The two isomeric cyclobutane-1,3-dicarboxylic acids are achiral and are optically inactive.
HO2 C H
H H
H HO 2C
trans CO2H cis CO2H
3.9 Mycomycin contains no chiral carbon atoms, yet it is chiral. To see why, make a model of
mycomycin. For simplicity, call -CH=CHCH=CHCH2CO2H "A" and –C= CH "B". Note that the carbon
atoms of an allene have a linear relationship and that the S bonds formed are perpendicular to each
other. Attach substituents at sp2 carbons.
Notice that the substituents A, Ha, and all carbon atoms lie in a plane that is perpendicular to the
plane that contains B, Hb, and all carbon atoms.
Now, make another model identical to the first, except for an exchange of A and HA. This new allene
is not superimposable on the original allene. The two allenes are enantiomers and are chiral
because they possess no plane of symmetry.
3.10 4-Methylcyclohexylideneacetic acid is chiral for the same reason that mycomycin is chiral: it
possesses no plane of symmetry and is not superimposable on its mirror image. As in the case of
allenes, the two groups at one end of the molecule lie in a plane perpendicular to the plane that
contains the two groups at the end.
CO 2H CO 2H
H 3C H
C C C C
H H 3C
H H
3.11 The reaction proceeds by addition of acetylide anion to the carbonyl group and occurs with
equal probability from either side of the planar ketone carbon.
O OH
S H 3O+ S
C C
H3 C H3 C
CH2 CH 3 CH2 CH 3
C C
O
HC HC
C
H 3C CH 2CH3
- C CH O OH
R H 3O+ R
C C
C C
HC CH2 CH 3 HC CH2 CH 3
H 3C H 3C
a) The product is an optically inactive racemic mixture.

b) The two enantiomers are formed in a 50:50 ratio.
c) Because these are enantiomers and have the same melting points, boiling points, solubilities
and polarities, they must be separated based on how differently they interact with other chiral
molecules. Therefore they can be separated by chiral chromatography.
3.12
H CH 3 H CH3
H CH 3
R C OH R C OH
C O R S
C 1. Na+ - C CH C C
H H
+
2. H3O + C C
H
(3R,4R)-4-phenyl- CH (3S,4R)-4-phenyl- CH
1-pentyn-3-ol 1-pentyn-3-ol
a) Reaction of sodium acetylide with a chiral aldehyde yields chiral products; the product
mixture is optically active.
b) The two products are a mixture of the (3R,4R) and (3S,4R) diastereomers of
4-phenyl-1-pentyn-3-ol. The product ratio cannot be predicted.
c) Because these are diasteomers and have different melting points, boiling points, solubilities
and polarities, they can be separated by using more conventional methods. Depending on their
physical state (solid/liquid), recrystallization, distillation, or column chromatography can be used.
3.13
x A and B are diastereomers

x A and C are identical (both are R) - or can be called conformers
x A and D are enantiomers
x A and E are constitutional isomers
3.14
c) 7 stereogenic centers, 27 = 128 possible stereoisomers

d) N1 = sp2, N2 = sp3
e) No, since there are no O - H bonds or N - H bonds present.
f) N2 is more basic than N1 since the lone pair on N2 is in a sp3 orbital, whereas the lone pair on
N1 is in a sp2 orbital. Therefore the lone pair in the sp3 orbital is less tighly held to the N due to
the s-character of the sp3 orbital, making them more basic (nucleophilic).
3.15 a)
i)
ii) All four structures are chiral.
iii) 1,2 and 3,4 are enantiomer pairs. 1,3 , 1,4 , 2,3 , 2,4 are diastereomer pairs.
b) i)
H 3C H 3C
H H
C C
H 3C
1 CH3
H 3C
2 CH3
H 3C H 3C
H H
C C
3 CH3 4 CH3
H 3C H 3C
ii) All four structures are chiral.
iii) 1,2 and 3,4 are enantiomer pairs. 1,3 , 1,4 , 2,3 , 2,4 are diastereomer pairs.
c) i)
ii) Structures 1-8 are chiral, and due to a plane of symmetry, structures 9 and 10 are achiral
meso structures.
iii) 1,8 , 2,6 , 3,7 , 4,5 are enantiomer pairs. All other relationships are diastereomers.
3.16
a) 3,4 are enantiomers. 1 and 2 are meso structures.
c) The C3 of the meso compounds is not asymmetric because it is not attached to four different
groups. Therefore, C3 is not a chirality center. But, C3 of this meso compound is a stereocenter since
the interchange of two of the groups on C3 gives a stereoisomer.
d) The C3 in the enantiomers is not asymmetric because it is not attached to four different
groups. Therefore, it is not a chiral center. It is also not a stereocenter, because if you interchange
two groups, you get the same compound. Such as:
same compound
Br Br Br Br
Br Br
(2R,4R)-2,3,4-tribromopentane
3.17
COOH COOH
HO HO
* *
H H
H H
1 2
a) There are no asymmetric carbons. i.e. no carbons with four different groups attached to it.
But, the C* is a stereocenter because as shown above, if you interchange two groups on the C*,
it gives a stereoisomer.
b) Both compounds 1 and 2 are chiral and are optically active in pure form. Since the student
obtained optically active product, then she must have a pure sample of either 1 or 2. Therefore
the enzyme she used is stereospecific – it specifically produces one stereoisomer from this
reaction.
c) The Ni catalyst is not stereospecific, therefore if the reduction was done with H2 and a Ni
catalyst, you would get a 50:50 mixture of 1 and 2 because the H2 adds syn on either side of the
C = O. Since a 50:50 racemic mixture of products are created, the product is optically inactive.
COOH
HO
H
COOH H
H2 1
O
Ni
H COOH
HO
H
H
2
3.18 The product of the reduction of compound A is chiral and therefore optically active. The
reduction of compound B forms a product which has a plane of symmetry, and is an achiral,
optically inactive meso compound. So, compound B is D-(-)-erythrose.
H OH H OH
HO CHO HO
H2
OH
Ni
H OH H OH
compound A
H OH H OH
HO CHO HO
H2
Ni OH
HO H HO H
compound B
3.19 Label each pair of molecules below as: enantiomers; identical, structural isomers, cis-
trans isomers, configurational isomers or unrelated (not isomers). And determine
whether a 50:50 mixture of the two are optically active of not.
Pair of molecules Relationship between 50:50 Mixture of the
the two molecules: two compounds are
optically active?
(yes/no)
No, because they are
enantiomers – their
Enantiomers
rotate the same
amount but in opposite
directions therefore
(S) (R)
they cancel out.
Yes, because each are
optically active.
Configurational isomers
No, because this

compound is a meso
Identical
compound, therefore is
optically inactive.
Yes, because this

compound is optically
Identical
active.
(they are conformers)

Section 3 - Stereochemistry

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Section 3 - Stereochemistry

Uploaded by

Copyright:

Available Formats

Section 3 - Problems

CH3 CH3 CH3

2 HSCH2CHCO2H HO2CCHCH2S SCH2CHCO2H

a) How many chirality centers does ribose have? Identify them.

a) Is the product chiral? Is it optically active?

Artemisinin Mefloquine CF3

a) Locate the stereogenic centers in both drugs.

3.15 For each structure,

3.1 a) (2S, 3R)-3-Methyl-pentan-2-ol b) (3S, 4S)-2,4-Dimethyl-hexan-3-ol

c) (2R, 3S)-3-Methyl-pentan-2-ol d) (S)-2-Ethyl-pentanoic acid

Problem Structural isomer Cis-trans isomer Enantiomer Rotamer

(many answers (or diastereomer) (many answers

other answer exists

other answer exists

Not applicable Not applicable Not applicable

other answers exist

other answers exist

Ribose has 3 chirality centers, which give rise to 2(3) = 8 stereoisomers.

Ribose has 6 diastereomers:

trans CO2H cis CO2H

a) The product is an optically inactive racemic mixture.

x A and B are diastereomers

c) 7 stereogenic centers, 27 = 128 possible stereoisomers

ii) All four structures are chiral.

ii) All four structures are chiral.

a) 3,4 are enantiomers. 1 and 2 are meso structures.

No, because this

Yes, because this

You might also like