STEREOCHEMISTRY Dr. Sheppard CHEM 2411 Spring 2015 Klein (2 nd ed.) sections 5.1-5.9, 8.4.
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Transcript of STEREOCHEMISTRY Dr. Sheppard CHEM 2411 Spring 2015 Klein (2 nd 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?
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:
W
C
ZY
X
W
C
ZY
X* *
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
C H
H
H
C CH3
H
H
C OH
H
H
highest
• Continue process until first point of difference
• Some more examples:
CH2
higher
CH2 CH2 CH2 CH3 CH2 CH2 CH2 CH2 NH2
Priority Rules
3. Atoms in double bonds count twice; atoms in triple bonds count three times
CH CH2C C H
C
O
OH C N
bonded to H, C, C bonded to C, C, C
bonded to O, O, O bonded to N, N, N
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
C
CH3 CH2CH3
C
CH3CH3CH2
BrBrH H
* *
1 1
23
4 4
2 3
(R)-2-bromobutane (S)-2-bromobutane
Rank the following groups in order of priority from highest (1) to lowest (4):
-NHC(O)CH3
-OCH3
-OH
-F
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
CH3 H H CH3
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
C
CH3
H
BrCl
rotateC
CH3
Br
ClH
Determine whether the two structures in each pair represent constitutional isomers, enantiomers, or identical compounds.
a)
b)
CH3
C
Br
ClH
C ClH
Br
CH3
CH2CH3
C
H
BrCH3
CH3
C
CH2CH3
HBr
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
C ZX
W
Y
ZX
W
Y
is the same as
Molecules With Multiple Stereocenters• Maximum # stereoisomers = 2n where n = # stereocenters
# Stereocenters # Stereoisomers Stereoisomers
1 2RS
2 4
(R,R)(S,S)(R,S)(S,R)
Example: 2,3-Pentanediol
• Draw Fischer projections for the 4 stereoisomers• Carbon chain vertical, C1 at top
CH3 CH CH CH2CH3
OHOH
* *
CH3
HO H
CH2CH3
H OH
CH3
H OH
CH2CH3
HO H
CH3
HO H
CH2CH3
HO H
CH3
H OH
CH2CH3
H OH
C2
C3
A B C D
2R,3R 2S,3S 2R,3S 2S,3R
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
CH3
HO H
CH2CH3
H OH
CH3
H OH
CH2CH3
HO H
CH3
HO H
CH2CH3
HO H
CH3
H OH
CH2CH3
H OH
C2
C3
A B C D
2R,3R 2S,3S 2R,3S 2S,3R
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 diastereomersCH3
H H
CH3 CH3
H CH3
H
CH3
HO H
CH2CH3
H OH
CH3
HO H
CH2CH3
HO H
A C
2R, 3R 2R, 3S
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
CH3
HO H
CH3
H OH
CH3
H OH
CH3
HO H
CH3
HO H
CH3
HO H
CH3
H OH
CH3
H OH
A B C D
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)
H H
prochiralcenter
pro-R
pro-S
Br2
h
Br H H Br
+
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
O
OH
OO
Thalidomide
• How many chirality centers?• How many stereoisomers?• How was the drug administered?• What effect did this have on
patients who used thalidomide?
N
N
O
O O
O
H
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