Stereochemistry I Chemistry 355
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Stereochemistry I
Chemistry 355
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Stereochemistry• Refers to the spatial arrangement of
atoms.• Stereochemistry is described in several
terms.
– Relative configuration• Relative to a standard compound
• Relative to another function in the molecule
– Absolute configuration• Refers to absolute arrangement in space for
enantiomers
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Relative Stereochemistry• Cis
– Rings
– Alkenes
• Z (zussamen – together)
• Trans
– Rings
– Alkenes
• E (entgegen – opposite)
NH2
NH2
NH2
NH2
H R
HR
H H
RR
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Relative Stereochemistry• Syn
– Same side – Erythro (sugars)
– Absolute assignments
preferred
• Anti
– Opposite side – Threo (sugars)
R
R NH2
NH2
R
R
NH2H
HH2N
≡
R
R
NH2H
HH2N
≡
R
R NH2
NH2
R
R
HH2N
HH2N
≡
R
R
HH2N
HH2N
≡
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Absolute Stereochemistry atTetrahedral Atoms
• Chirality
– Non-superimposeable – Mirror images
– Requires 4 different
groups – May or may not be
stable (Amines)
– Called enantiomers
– Configuration R or S
– Build these models
(R)
OH
(S)
OH
mirror
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Absolute Configuration• Cahn-Ingold-Prelog
– Prioritize substituents
• Highest atomic #• When two of same, go one
atom further
• Place lowest prioritysubstituent to rear
– Multiple bonds are treated astwo substituents
• C=O is treated as O-C-O
– Sense of direction
• Down priority list 1-3• R – rectus – Right (clockwise)
• S – sinistere – Left (CCW)
C C
C
OH
mirror
H
1
23
4H
R
C C
C
OH
H
1
23
4H
S
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Diastereomers
• Diastereomers have multiple stereocenters
• Differ by one or more, but not all configurationalcenters
(R)
(R)
NH2
OH
(S)
(R)
NH2
OH
(S)
(S)
NH2
OH
(R)
(S)
NH2
OH
mirror
E
n a n t i o m e r s
E n a n t i om e r s
Diastereomers
Diastereomers
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meso -Compounds• A meso -compound (syn. mesosteroisomer,
mesomer) is a diastereomer which is the same as
it’s mirror image and therefore not chiral (achiral).
(R)
(R)
NH2
NH2
(S)
(R)
NH2
NH2
(S)
(S)
NH2
NH2
(R)
(S)
NH2
NH2
mirror
E n a n t i o m e r s
Diastereomers
Diastereomers
S a m e m ol e c ul e
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meso -Compounds• Most meso -Compounds have internal mirror planes*
• One half of the molecule is the reflection of the other.
• The stereocenters effectively oppose one another
• Chiral molecules contain no mirror planes
Mirror plane2 stereocentersmeso
achiral
Mirror planeNo stereocentersNot meso
achiral
NH2
NH2
mirror H
Cl
CH3
Cl
mirrorR
S
*Note: For true meso -compounds, these planes exist in representation only. In reality, they are often conformers thatinterconvert rapidly on a laboratory timescale. There are examples that do not and are chiral (atropisomers). The precisedefinition of a mesomer is an achiral member of a set of diastereomers that includes at least one chiral member.
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Absolute Configuration• Use models
– Physical models
• Hand model (free and always withyou)
• Styrofoam balls and toothpicks(cheap)
• Model Kit ($10-$50 but worth
every penny) – available for usein class. May be checked out.
– Virtual model• Chem3D
• Hyperchem
• RasMol• Online versions available
• Freeware
• Best in conjunction with a physicalmodel
C C
C
OH
mirror
H
1
23
4H
R
C C
C
OH
H
1
23
4H
S
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Optical Rotation• Chiral compounds have a property called helicity
• When light interacts with the molecule it is rotated
slightly with respect to the incident light.• This is observed by irradiating with light that has
been plane polarized using filters
SampleH
CH3
Cl
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Polarimetry• 2 polarizing filters
• 1 rotatable
• Measure angle ofrotation on scale
• Sample rotation
α Tλ
• Specific rotationα
[α] Tλ
Tλ
c l
=
concentration in g/mLlength in decimeters
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Specific Rotation• Defined temperature
• Defined wavelength
– Sodium D line
– 589 nm
– Often denoted as subscript D
• Rotation at 25oC at 589 nmwith a concentration of 2grams per 100 mL in ethanol
[α]25D
25.3 (c = 2, EtOH)
α
[α] Tλ
Tλ
c l=
c is concentration in g/mLdensity for neat liquids
(NOTE: reported as g/100mL)
l is cell length in decimeters
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Wavelength Dependence
• Optical rotation is dependent on wavelength
• Depends on absorbance (ε)
• Light interacts with various features
• Greater ε leads to greater rotation
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Stereochemical effects• Stereochemistry is involved many chemical reactions
– As a consequence (creation of a new stereocenter)
– As an influence (diastereoselection)
• It is intimately linked to the mechanism of reactions
• Stereocenters may be created, destroyed or altered
CH3
OH
CH3
HH HO
+
Reduction
CH3
OHH
OxidationCH3
O
CH3
O
SubstitutionCH3
HX
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Substitution
CH3
H-OH
SN2 CH3
HBr OH
CH3
OH
CH3
HH HO
+
SN1
CH3
OH
H
Br
CH3
H+
-
-H+
H2O inversion
racemization
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Elimination
CH3
Br
H3C
Ph
H
H
Ph
Ph
CH3
Ph
H
Ph
CH3
H
Ph
H3C
Ph
H
H
Ph
Br
Ph
CH3
Ph
H
tBuO-
E2H2SO4
E1
+
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EliminationO
O
O
O
O
TsO
H
H
O
O
O
O
O
H
O
O
O
O
O
H
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EliminationO
O
O
O
O
TsO
H
H
O
O
O
O
O
H
O
O
O
O
O
H
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Reduction
Ph CH3
OH
Ph CH3
HH HO
+
BH3
CH3
O
CH3
OHH
BR2
CH3
H
B
H
R R
O
CH3
CH3
Ph
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Nucleophilic attack
O
OH
CH3
O
OH
CH3
H-
CH3Li
O
CH3
OH
CH3Li