Unit 3 – Stereochemistry
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Stereoisomers
Chirality
(R) and (S) Nomenclature
Depicting Asymmetric Carbons
Diastereomers
Fischer Projections
Stereochemical Relationships
Optical Activity
Resolution of Enantiomers
Stereochemistry
 Stereochemistry:
 The study of the three-dimensional
structure of molecules
 Structural (constitutional) isomers:
 same molecular formula but different
bonding sequence
 Stereoisomers:
 same molecular formula, same bonding
sequence, different spatial orientation
Stereochemistry
CH3
O
 Stereochemistry plays an important role in
determining the properties and reactions of
H
organic compounds:
H3C
CH3
CH3
O
H3C
CH2
H
CH2
Caraway seed
O
H
H2C
CH3
spearmint
Stereochemistry
 The properties of many drugs depends on their
stereochemistry:
HN
O
O
CH
CH3
NH3NH
O
NHCH3
Cl
HN
Cl
Cl
O
CH3NH
Cl
(S)-ketamine
(R)-ketamine
anesthetic
hallucinogen
Stereochemistry
 Enzymes are
capable of
distinguishing
between
stereoisomers:
Types of Stereoisomers
 Two types of stereoisomers:
 enantiomers
 two compounds that are nonsuperimposable
mirror images of each other
 diastereomers
 Two stereoisomers that are not mirror
images of each other
 Geometric isomers (cis-trans isomers) are
one type of diastereomer.
Chiral
 Enantiomers are chiral:
 Chiral:
 Not superimposable on its mirror image
 Many natural and man-made objects are chiral:
 hands
 scissors
 screws (left-handed vs. right-handed threads)
Right hand threads
slope up to the right.
Chiral
 Some molecules are chiral:
Asymmetric
(chiral) carbon
Asymmetric Carbons
 The most common feature that leads to
chirality in organic compounds is the presence
of an asymmetric (or chiral) carbon atom.
 A carbon atom that is bonded to four
different groups
 In general:
 no asymmetric C
 1 asymmetric C
 > 2 asymmetric C
usually achiral
always chiral
may or may not be
chiral
Asymmetric Carbons
Example: Identify all asymmetric carbons
present in the following compounds.
H
Br
H
OH H
H
C
C
C
C
H
H
H
H
H
H
H3C
CH3
CH2CH3
H
H
Br
Br
Br
H CH
3
Achiral
 Many molecules and objects are achiral:
 identical to its mirror image
 not chiral
H
H
Cl Cl
H
H
Cl Cl
Internal Plane of Symmetry
 Cis-1,2-dichlorocyclopentane contains two
asymmetric carbons but is achiral.
 contains an internal mirror plane of
symmetry
s
H
H
Cl
Cl
 Any molecule that has an internal mirror plane
of symmetry is achiral even if it contains
asymmetric carbon atoms.
Internal Plane of Symmetry
 Cis-1,2-dichlorocyclopentane is a meso
compound:
 an achiral compound that contains chiral
centers
 often contains an internal mirror plane of
symmetry
Internal Plane of Symmetry
Example: Which of the following compounds contain
an internal mirror plane of symmetry?
HO2C
HO
H
C
HO2C
HO
H
C
C
CO2H
OH
H
C
H Br
CH2CH3
C
H3CH2C
CO2H
H
OH
F
HO
C
H
Br
O
C OHF
C H
H
CH3
H
H3C
H
C
F
Cl
H
Chiral vs. Achiral
 To determine if a compound is chiral:
 0 asymmetric carbons:
Usually achiral
 1 asymmetric carbon:
Always chiral
 2 asymmetric carbons:
Chiral or achiral
 Does the compound have an internal plane
of symmetry?
– Yes:
achiral
– No:
– If mirror image is nonsuperimposable, then it’s chiral.
– If mirror image is superimposable,
then it’s achiral.
Conformationally Mobile Systems
 Alkanes and cycloalkanes are conformationally
mobile.
 rapidly converting from one conformation to
another
 In order to determine whether a cycloalkane is
chiral, draw its most symmetrical conformation
(a flat ring).
Chiral vs. Achiral
Br
Br
H
CHthe
3
Example: Identify
following molecules as
chiral or achiral.
CH3 C CH2CH3
Cl
CH3CHCH2CH2CH3
CH3
l
H
H
Br
Br
H
Cl
CH3
CH3CH2
CH3CCH2CH3
Cl
Br
H
Br
H
trans-1,3-dibromocyclohexane
CH2CHethylcyclohexane
3
H
Br
H
C
C
Br
CH2CH3
(R) And (S) Nomenclature
 Stereoisomers are different compounds and
often have different properties.
 Each stereoisomer must have a unique name.
 The Cahn-Ingold-Prelog convention is used to
identify the configuration of each asymmetric
carbon atom present in a stereoisomer.
 (R) and (S) configuration
(R) and (S) Nomenclature
 The two enantiomers of alanine are:
H3C
CO2H
CO2H
C
C
H
NH2
Natural alanine
(S)-alanine
H
H2N
CH3
Unnatural alanine
(R)-alanine
(R) and (S) Nomenclature
 Assign a numerical priority to each group
bonded to the asymmetric carbon:
 group 1 = highest priority
 group 4 = lowest priority
 Rules for assigning priorities:
 Compare the first atom in each group (i.e.
the atom directly bonded to the asymmetric
carbon)
 Atoms with higher atomic numbers have
higher priority
(R) and (S) Nomenclature
Cl 1
3
C 2
H3 C
OCH2CH3
H
4
3
CH3
C H4
NH2
1 F
2
Example priorities:
I > Br > Cl > S > F > O > N >
1H
13C
>
12C
> 3H > 2H >
(R) and (S) Nomenclature
 In case of ties, use the next atoms along the
chain as tiebreakers.
2 CH CH Br
2
2
C
3 CH CH
2
3
H4
CH(CH3)2
1
CH(CH3)2 > CH2CH2Br > CH3CH2
Y
C Y
(R) and (S)
Nomenclature
C Y
Y
C
C
C
Y
 Treat double and
triple bonds as if both atoms
C Y
Y
or triplicated:
O in the bondC were
C
C Yduplicated
O
C
C
H
H
Y
OH
C Y
CH2OH
C
Y
C
Y
Y
C
O 2 H
Y C
1
C C OH
4 H CH2OH
3
C
Y
Y
C
C
C
Y
Y
C
C O
Y
C Y2
O C H
C
C 4 HY
C
Y C
1
OH
CH2OH
Y3
Y
Y
C
C
Y
C
Y
C
C
(R) and (S) Nomenclature
 Using a 3-D drawing or model, put the 4th
priority group in back.
 Look at the molecule along the bond between
the asymmetric carbon and the 4th priority
group.
 Draw an arrow from the 1st priority group to
the 2nd group to the 3rd group.
 Clockwise arrow
 Counterclockwise arrow
(R) configuration
(S) configuration
(R) and (S) Nomenclature
CH3)2
Example: Identify the asymmetric carbon(s) in
each of the following compounds and determine
whether it has the (R) or (S)Oconfiguration.
CH3
CH3
C
CH2C
CH3
CH2CH3
OHH
OH
H3
Br
C
CH3
H
H
C
CH3 Br
O
CO2H
H
H
CH(CH3)2
Br
CH3
COH
CH2C
H OH
(R) and (S) Nomenclature
Example: Name the following compounds.
CH2CH3
Br
H
C
CH3
Br
CH3
H
CH3
(R) and (S) Nomenclature
 When naming compounds containing multiple
chiral atoms, you must give the configuration
around each chiral atom:
 position number and configuration of each
chiral atom in numerical order, separated by
commas, all in ( ) at the start of the
compound name
H Br
H3C
H
Cl
CH3
(2S, 3S)-2-bromo-3-chlorobutane
Depicting Structures with Asymmetric
Carbons
Example: Draw a 3-dimensional formula for (R)2-chloropentane.
Step 1: Identify the asymmetric carbon.
Cl
CH3 C* CH2CH2CH3
H
Step 2: Assign priorities to each group attached to
the asymmetric carbon.
1
C
Cl
2
3 CH C CH CH CH
2
3
H 4
2
3
Depicting Structures
with Asymmetric
Cl
Carbons
CH3 C
CH2CH2CH3
Step 3: Draw a “skeleton” with the asymmetric carbon
in the center and H
the lowest priority group attached to
the “dashed” wedge (i.e. pointing away from you).
Cl
CH3 C
C
CH
H 2CH2CH3
H
Step 4: Place the highest priority group at the top.
Cl
H
C
Depicting Structures with Asymmetric
Cl
Carbons
CH3
CH5:
CForCH
Step
(R)2CH
configuration,
place the 2nd and
2
3
3rd priority groups around the asymmetric
H
carbon in a clockwise direction.
Cl
H
C
CH3 CH2CH2CH3
Step 6: Double-check your structure to make
sure that it has the right groups and the right
configuration.
Depicting Structures with Asymmetric
Carbons
Example: The R-enantiomer of ibuprofen is not
biologically active but is rapidly converted to the
active (S) enantiomer by the body. Draw the
structure of the R-enantiomer.
HO2CCH
CH3
CH2CH(CH3)2
Depicting Structures with Asymmetric
Carbons
Example: Captopril, used to treat high blood
pressure, has two asymmetric carbons, both with
the S configuration. Draw its structure.
O
N
CO2H
C
CHCH2SH
CH3