Unit 3 – Stereochemistry
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Transcript Unit 3 – Stereochemistry
Unit 3 – Stereochemistry
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
3 CH C
3
H 4
2
CH2CH2CH3
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