Post on 27-Mar-2015
StereochemistryStereochemistry
Paderborn, May 2005Paderborn, May 2005
Founding Fathers ofFounding Fathers of Stereochemistry Stereochemistry
BiotBiot: The solutions of : The solutions of many naturally occurring many naturally occurring compounds rotate the compounds rotate the plane of plane of polarizationpolarization of of polarized light (1815-1817)polarized light (1815-1817)
PasteurPasteur recognized in recognized in 1850 that this 1850 that this optical optical activityactivity was caused by an was caused by an asymmetric arrangement asymmetric arrangement of atoms in a moleculeof atoms in a molecule
van’t Hoffvan’t Hoff and and Le BelLe Bel described in 1874 how the described in 1874 how the atoms of a molecule are atoms of a molecule are actually arranged in actually arranged in spacespace
BiotBiot
PasteurPasteur
Van’t HoffVan’t Hoff
Subdisciplines of StereochemistrySubdisciplines of Stereochemistry
Static stereochemistryStatic stereochemistry• Studies the three-dimensional Studies the three-dimensional
arrangement of the atoms of a molecule in arrangement of the atoms of a molecule in the ground statethe ground state
Dynamic stereochemistryDynamic stereochemistry• Description of the steric relationships in Description of the steric relationships in
molecules as they change from one state molecules as they change from one state to another, for example during a chemical to another, for example during a chemical reactionreaction
PreviewPreview
IntroductionIntroduction Conformational analysisConformational analysis
• CyclohexaneCyclohexane• Bicyclic compounds, steroidsBicyclic compounds, steroids• Heterocyclic compoundsHeterocyclic compounds
Optical activityOptical activity and stereoisomerism and stereoisomerism• Symmetry and chiralitSymmetry and chiralityy• Molecular asymmetryMolecular asymmetry• ProchiralityProchirality
Chiroptical properties of chiral moleculesChiroptical properties of chiral molecules• Optical rotatory dispersionOptical rotatory dispersion
IntroductionIntroduction
Structure: Structure: Includes bothIncludes both constitution and configuration.constitution and configuration. Constitution:Constitution: Describes the kinds and order of the Describes the kinds and order of the
bonds and atoms or atom groups in a compound.bonds and atoms or atom groups in a compound. Configuration:Configuration: Describes the different spatial Describes the different spatial
arrangements of atoms or atom groups of a compound arrangements of atoms or atom groups of a compound with a given constitution.with a given constitution.• StereoisomerismStereoisomerism
Enantiomers: Enantiomers: Image and mirror image are not identicalImage and mirror image are not identical Diastereomers: Diastereomers: Stereoisomers that are not mirror imagesStereoisomers that are not mirror images
Conformation:Conformation: Describes the different spatial Describes the different spatial arrangements of atoms or groups in a molecule that arrangements of atoms or groups in a molecule that arise due to rotation (torsion) around single bondsarise due to rotation (torsion) around single bonds..
ExamplesExamples
Structure and Constitution:Structure and Constitution:
Configuration:Configuration:
H
CH3
H3C
H
CH3
H
H3C
H
and
have the same constitution, but differ in the spatial arrangement of their substituents -> Stereoisomers
HCH3C
OH
CO2HLactic acid has two stereoisomers:
CO2H
COHH3C
H
CO2H
CHO CH3
H
Muscle lactic acid:(+) rotation
Fermentation lactic acid:(-) rotation
Physical and chemical properties are identical,only optical rotation differs
ExamplesExamples Configuration:Configuration:
• StereoisomerismStereoisomerism Enantiomers: Enantiomers: Image and mirror image are not identicalImage and mirror image are not identical Diastereomers: Diastereomers: Stereoisomers that are not mirror imagesStereoisomers that are not mirror images
CO2H
H OH
H OH
CO2H
CO2H
HO H
HO H
CO2H
CO2H
H OH
HO H
CO2H
CO2H
HO H
H OH
CO2H
Mirror plane Mirror plane
(+)-Tartaric acid (-)-Tartaric acid meso-Tartaric acid
mp. 174oC mp. 151oC
Enantiomers Identical!
Diastereomers
Conformation: EthaneConformation: Ethane
H
HH
H
HH
H
HH
HH
H
Eclipsed Staggered
H
H H
H H
H
H
H H
H
H H
60o
Conformation: EthaneConformation: Ethane
H
HH
H
HH
H
HH
H
HH
H
HH
H
HH
H
HH
H
HH
H
HH
HH
H
H
HH
HH
H
H
HH
HH
H
Conformational AnalysisConformational Analysis
CyclohexaneCyclohexane Bicyclic systems and steroidsBicyclic systems and steroids Heterocyclic systemsHeterocyclic systems
Optical activityOptical activity and Stereoisomerism and Stereoisomerism
Symmetry und chiralitySymmetry und chirality• Symmetry axis CSymmetry axis Cnn
• Symmetry plane Symmetry plane σσ• Symmetry centre Symmetry centre ii• Rotation/reflection axis SRotation/reflection axis Snn
Molecular asymmetryMolecular asymmetry• Chiral axisChiral axis• Chiral planeChiral plane• Chiral cChiral centreentre
ProchiralityProchirality
Symmetry and ChiralitSymmetry and Chiralityy
nn–Fold axis of symmetry C–Fold axis of symmetry Cnn
Plane of symmetry Plane of symmetry σσ
Cl
FIBr
H
ClClCl
H
O
H
H
HH
H
Cl
H
Symmetry and ChiralitSymmetry and Chiralityy
Centre of symmetryCentre of symmetry ii
nn-Fold-Fold rotation-reflection axis rotation-reflection axis SSnn
HO
CO2H
H OH
HO2HC
i
OH
CO2HH OH
HHO2C
OH
HO2C H
OH
H CO2H
OH
CO2HH OH
HHO2C
Symmetry and ChiralitSymmetry and Chiralityy
Molecules with no reflection symmetry are Molecules with no reflection symmetry are chiralchiral A molecule with only aA molecule with only a C Cnn axis is chiral axis is chiral
Molecular AsymmetryMolecular Asymmetry
Chiral axisChiral axis Chiral planeChiral plane Chiral centreChiral centre
Chiral AxisChiral Axis
C
C
C
ba
a b
Ca b
n(H2C)
C
(CH2)n
C
a b
Allene Alkylidenecycloalkane
Chiral PlaneChiral Plane
O O
Br
H2C CH2
(CH2)n
1.1. Lead atom: atom with highest priority directly Lead atom: atom with highest priority directly linked to the planelinked to the plane
2.2. Determine the atom sequence in the planeDetermine the atom sequence in the plane
3.3. Determine chirality, starting from the lead atomDetermine chirality, starting from the lead atom
11
22
33 RR
aa bbcc
Chiral CentreChiral Centre
CH3
CNHBr
CH3
Br
H
CN
ProchiralitProchiralityy
EnantiotoposEnantiotopos EnantiofacesEnantiofaces DiastereotoposDiastereotopos DiastereofacesDiastereofaces
HeterotopyHeterotopy
HomotopicHomotopic HeterotopicHeterotopic
• ConstitutopicConstitutopic• StereoheterotopicStereoheterotopic
EnantiotopicEnantiotopic DiastereotopicDiastereotopic
Substitution TestSubstitution Test
Identical moleculesIdentical molecules• Homotopic (equivalent)Homotopic (equivalent)
IsomersIsomers• HeterotopicHeterotopic
Constitutional isomersConstitutional isomers• ConstitutopicConstitutopic
StereoisomersStereoisomers• StereoheterotopicStereoheterotopic
EnantiomersEnantiomers• EnantiotopicEnantiotopic
DiastereomersDiastereomers• DiastereotopicDiastereotopic
Optical ActivitOptical Activity and Stereoisomerismy and Stereoisomerism
Chiroptical Properties of Chiral Chiroptical Properties of Chiral MoleculesMolecules
A linearly polarized wave may be described as A linearly polarized wave may be described as the result of a left polarized wave superimposed the result of a left polarized wave superimposed on a right polarized waveon a right polarized wave
Left and right polarized waves are absorbed Left and right polarized waves are absorbed differently by an optically active compounddifferently by an optically active compound
When the two components are recombined after When the two components are recombined after passing through an optically active medium, the passing through an optically active medium, the result is an elliptically polarized wave with result is an elliptically polarized wave with ellipticity θ:ellipticity θ:
Optical ActivityOptical Activity
Optically active compounds are Optically active compounds are circularly circularly birefringentbirefringent – the refractive indices of the – the refractive indices of the left and right polarized waves differ:left and right polarized waves differ:• v = c/n , therefore, if vv = c/n , therefore, if vL L ‡ v‡ vR R , then n, then nL L ‡ n‡ nR R
• There is a phase difference, resulting in There is a phase difference, resulting in optical rotation:optical rotation:
= = .d(n.d(nL L - n- nRR)/)/ = 180d(n = 180d(nL L - n- nRR)/)/
• The optical rotation is dependent on the The optical rotation is dependent on the wavelength wavelength – Optical rotatory dispersion– Optical rotatory dispersion
Anomalous curve
Chiroptical Properties of Chiral Chiroptical Properties of Chiral MoleculesMolecules
Optical rotatory dispersionOptical rotatory dispersion• Plain curvesPlain curves• Anomalous curvesAnomalous curves
Chiroptical Properties of Chiral Chiroptical Properties of Chiral MoleculesMolecules
Optical rotatory dispersionOptical rotatory dispersion• Achiral chromophoresAchiral chromophores• Chiral chromophoresChiral chromophores
Achiral ChromophoresAchiral Chromophores
NO2
HCH2
O
NO2
H
CH3
H
CH2
O
CH3
H
Achiral disturbanceAchiral disturbance
Chiral disturbanceChiral disturbance
Chiral ChromophoresChiral Chromophores
H
H
H
H O
+
Chiroptical Properties of Chiral Chiroptical Properties of Chiral MoleculesMolecules
Optical rotatory dispersionOptical rotatory dispersion• ConstitutionConstitution• ConfigurationConfiguration• ConformationConformation
Plain CurvesPlain Curves
With small amounts of substance, one can With small amounts of substance, one can measure at shorter wavelengthsmeasure at shorter wavelengths
To determine whether a substance is To determine whether a substance is really optically active and not racemicreally optically active and not racemic
ExampleExample
OHMeO
N
N
MeO
NH
NH
O O
O
CO2H
Both not active at 589 nm
Inactive Active, [M] = -165o at 365 nm
Racemic Not racemic
ORD of Steroids: ConstitutionORD of Steroids: Constitution
Me
Me
H
H
O
AB
C
Chiroptical Properties of Chiral Chiroptical Properties of Chiral MoleculesMolecules
Optical rotatory dispersionOptical rotatory dispersion• ConstitutionConstitution• Configuration and conformationConfiguration and conformation
Cis/transCis/trans-Isomerism in Steroids: -Isomerism in Steroids: ConfigurationConfiguration
Me
MeOH
H
H
O
Me
MeOH
H
H
O
Me
MeOH
H
H
O
UnsaturatedUnsaturated Ketones and Diketones Ketones and Diketones
The Octant Rule forThe Octant Rule for Ketones Ketones
COCO11 22
33
4455
66
Octant RuleOctant Rule
Chiroptical Properties of Chiral Chiroptical Properties of Chiral MoleculesMolecules
• Octant rule:Octant rule: ConfigurationConfiguration ConformationConformation
• Absolute configurationAbsolute configuration
SummarySummary
IntroductionIntroduction Conformational analysisConformational analysis
• CyclohexaneCyclohexane• Bicyclic compounds, steroidsBicyclic compounds, steroids• Heterocyclic compoundsHeterocyclic compounds
Optical activity aOptical activity and stereoisomerismnd stereoisomerism• Symmetry and chiralitSymmetry and chiralityy• Molecular asymmetryMolecular asymmetry• ProchiralityProchirality
Chiroptical properties of chiral moleculesChiroptical properties of chiral molecules• Optical rotatory dispersionOptical rotatory dispersion
Questions/Remarks ?Questions/Remarks ?