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STEREOCHEMISTRY
Dr. Sheppard
CHEM 2411
Spring 2015
Klein (2nd ed.) sections 5.1-5.9, 8.4
Stereochemistry
• Branch of chemistry concerned with the spatial
arrangement of atoms in molecules
• Stereoisomers:
• Same molecular formula
• Same connectivity
• Different 3D orientation (cannot be converted via bond rotation)
• Previously:
• Cis and trans
• Now:
• Stereochemistry at tetrahedral centers
• Enantiomers, diastereomers
• E and Z
Chirality
• “handedness”
• Has a mirror image that is
nonsuperimposable
• Example: hand
• Example: sunglasses
Chiral or not?
Chiral or not?
Chirality
• A molecular example:
• Try this with your model kit
Achiral molecules
• Are superimposable on their mirror images
• Contain a plane of symmetry
• Cuts through the middle of the molecule so that one half reflects
the other half
achiral
chiral
Enantiomers
• Chiral molecules form enantiomers
• Nonsuperimposable mirror images
• Result from tetrahedral C (sp3) with 4 different substituents
• This C is called a chirality center (or stereocenter, or
asymmetric center) and are often marked with *
• Examples of stereocenters:
Enantiomers
• Example:
• (+) and (-)-lactic acid are a pair of enantiomers
Identify the chirality centers
Molecule
Stereocenter?
Plane of
Symmetry?
Chrial?
Molecule
Stereocenter?
Plane of
Symmetry?
• Not all molecules with stereocenters are chiral!
Chrial?
Enantiomer Similarities and Differences
• Same molecular formula, connectivity
• Different 3D arrangement
• Same physical properties (mp, bp,
solubility)
• Same spectroscopic properties (IR,
NMR, etc.)
• Same reactivity, in general
• Products will have different
stereochemistry
• Only one will react with an enzyme (like a
hand fitting in a glove)
• Different designations (R vs. S)
• Different optical activity
Optical Activity
• Rotation of plane-
polarized light
• Seen in chiral molecules
• a = observed rotation; measured by the polarimeter
• One enantiomer rotates light to the left a degrees
• Levorotatory (-)
• The other rotates light to the right a degrees
• Dextrorotatory (+)
Optical Rotation
• Depends on polarimeter pathlength (l) and sample
concentration (c)
• Specific rotation [a]D is observed under standard conditions
• l = 589.6 nm
• l = 1 dm (10 cm)
• c = 1 g/cm3
• (-)-Lactic acid has a [a]D of -3.82
• (+)-Lactic acid has a [a]D of +3.82
• What is [a]D of a 50:50 mixture of (-) and (+)-lactic acid?
R and S designations
• Used to describe 3D configuration about a chirality center
• Not related to direction of optical rotation (+) and (-)
• To designate R and S need to assign priorities to each
group bonded to the stereocenter
• Cahn-Ingold-Prelog system
Priority Rules
1. Higher atomic number (of atom bonded to C*) = higher
priority
-Br > -Cl > -OH > -NH2 > -CH3 > -H
2. If 2 of the same atom are bonded to C*, look at atomic
number of the next set of atoms
• Continue process until first point of difference
• Some more examples:
Priority Rules
3. Atoms in double bonds count twice; atoms in triple
bonds count three times
Which substituent has the higher priority?
a)
-Br
-Cl
b)
-CH2CH3
-CH(CH3)2
c)
-CH=CH2
-CH2CH3
d)
-CHO
-CO2H
e)
-CH2OH
-CH2CH2OH
To designate R or S:
1. Locate chirality center
2. Assign priority to the 4 groups (1 = highest; 4 = lowest)
3. Orient molecule so substituent 4 is point away from you
(with model or on paper)
4. Read the other groups 1→2→3 (draw arrow on paper)
5. Groups read clockwise = R; counterclockwise = S
Example: 2-bromobutane
Example: 2-bromobutane
Rank the following groups in order of
priority from highest (1) to lowest (4):
-NHC(O)CH3
-OCH3
-OH
-F
Draw R and S stereoisomers for
2-hydroxypropanal:
R and S stereoisomers for
3-methylhexane:
• Hints:
• Switch any two groups to draw the enantiomer
• When substituent 4 is forward, 1→2→3 clockwise is S
Classify these as chiral or achiral:
How many chirality centers?
Rotating a Tetrahedral Carbon
• To rotate a carbon and not accidentally change the R/S
designation, keep one substituent in the same place, and
rotate the other three.
• Make sure all three groups are rotating in the same direction
• Do not switch two groups; this changes the R/S designation
Classify these molecules as R or S:
Determine whether the two structures in
each pair represent constitutional isomers,
enantiomers, or identical compounds.
a)
b)
Fischer Projections
• Another way of drawing tetrahedral carbons
• Horizontal lines = out of page
• Vertical lines = into page
• Frequently used for chirality centers, especially if a
molecule has more than one chiral center
What is the relationship between
these two molecules?
Molecules With Multiple Stereocenters
• Maximum # stereoisomers = 2n where n = # stereocenters
# Stereocenters
# Stereoisomers
Stereoisomers
1
2
R
S
4
(R,R)
(S,S)
(R,S)
(S,R)
2
Example: 2,3-Pentanediol
• Draw Fischer projections for the 4 stereoisomers
• Carbon chain vertical, C1 at top
Relationships
• A and B are enantiomers
• C and D are enantiomers
• A and C, A and D, B and C, B and D are diastereomers
Diastereomers
• Stereoisomers that are not mirror images of each other
• Different physical properties
• With tetrahedral carbons, require at least 2 stereocenters
• Cis-trans stereoisomers are also diastereomers
Meso Compounds
• Maximum # stereoisomers = 2n where n = # stereocenters
• The # stereoisomers will be less than 2n when there is a
meso compound
• Meso compound
• An achiral compound which contains chirality centers
• Not optically active
• The chirality centers typically are identical (have the same 4
substituents) and reflect each other in a plane of symmetry
• Example:
Another Example: 2,3-Butanediol
• A = (2R,3R)-2,3-butanediol
• B = (2S,3S)-2,3-butanediol
• C = D = meso-2,3-butanediol
• C and D are superimposable mirror images (the same molecule)
• Relationship between enantiomers and meso?
• Diastereomers
Racemic Mixtures
• aka Racemate, + pair, or d,l pair
• 50% mixture of two enantiomers
• Not optically active
• Separation of enantiomers is difficult
• Separation methods:
• React with chiral compound to convert to a pair of diastereomeric
salts, which can be separated by distillation, crystallization, etc.
• Separate on chiral column
• Separate with enzyme
Applications of Stereochemistry
1. Stereochemistry of reactions
• If a product has a stereocenter, is the stereochemistry all
R, all S, or a mixture?
• To understand details, need to look at mechanism (next)
Applications of Stereochemistry
2. Reactions with enzymes
• Receptors/enzymes react with only one enantiomer (like a
handshake)
• Limonene
• R = orange odor
• S = pine odor
• Ibuprofen
• R = inactive
• S = active
• D-Decalactone
• R = porcupine emits to alert predators
• S = coconut
Thalidomide
• How many chirality centers?
• How many stereoisomers?
• How was the drug administered?
• What effect did this have on
patients who used thalidomide?
Francisco Goya
Alkene Stereochemistry
• Previously, cis-trans stereoisomers
• Now, E,Z-designation of alkenes
• Use E,Z instead of cis-trans when
• More than two substituents on C=C
• Heteroatoms on C=C
• To assign E or Z:
• Rank the two groups on each carbon of the C=C according to the
Cahn-Ingold-Prelog priority rules
• If the higher priority groups are on the same side of the C=C, the
alkene has Z geometry
• If the higher priority groups are on opposite sides of the C=C, the
alkene has E geometry
E and Z Configurations
Classify these alkenes as E or Z:
a)
b)
Name these alkenes:
a)
b)
Isomerism Worksheet
Next…
• Organic reactions