Stereochemistry Paderborn, May 2005. Founding Fathers of Stereochemistry Biot: The solutions of many naturally occurring compounds rotate the plane of.

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


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


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


Optical rotatory dispersionOptical rotatory dispersion• Plain curvesPlain curves• Anomalous curvesAnomalous curves


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

+


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


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


• 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 ?

Stereochemistry Paderborn, May 2005. Founding Fathers of Stereochemistry Biot: The solutions of many naturally occurring compounds rotate the plane of.

Documents

chiral slide

chiral axis slide

images slide

reflection symmetry

ethane slide

c n axis

mirror image

chemical reaction slide