Stereochemistry

Paderborn, May 2005

Founding Fathers of Stereochemistry

Biot

Biot: The solutions of many naturally occurring compounds rotate the plane of polarization of polarized light (18151817) Pasteur recognized in 1850 that this optical activity was caused by an asymmetric arrangement of atoms in a molecule vant Hoff and Le Bel described in 1874 how the atoms of a molecule are actually arranged in space

Pasteur

Vant Hoff

Subdisciplines of Stereochemistry

Static stereochemistry
Studies the three-dimensional arrangement of the atoms of a molecule in the ground state

Dynamic stereochemistry
Description of the steric relationships in molecules as they change from one state to another, for example during a chemical reaction

Preview

Introduction Conformational analysis

Cyclohexane Bicyclic compounds, steroids Heterocyclic compounds

Optical activity and stereoisomerism

Symmetry and chirality Molecular asymmetry Prochirality

Chiroptical properties of chiral molecules

Optical rotatory dispersion

Introduction

Structure: Includes both constitution and configuration. Constitution: Describes the kinds and order of the bonds and atoms or atom groups in a compound. Configuration: Describes the different spatial arrangements of atoms or atom groups of a compound with a given constitution.
Stereoisomerism

Enantiomers: Image and mirror image are not identical Diastereomers: Stereoisomers that are not mirror images

Conformation: Describes the different spatial arrangements of atoms or groups in a molecule that arise due to rotation (torsion) around single bonds.

Examples

Structure and Constitution:

H
CH 3 and H3C H H3C CH 3 H H have the same constitution, but differ in the spatial arrangement of their substituents -> Stereoisomers

Configuration:
Lactic acid H3C H C OH CO2H H H3C C OH HO CO2H C H CH3 CO2H has two stereoisomers:

Muscle lactic acid: (+) rotation

Fermentation lactic acid: (-) rotation

Physical and chemical properties are identical, only optical rotation differs

Examples

Configuration:
Stereoisomerism

Enantiomers: Image and mirror image are not identical Diastereomers: Stereoisomers that are not mirror images
OH CO2H CO2H CO2H H HO H HO CO2H CO2H H CO2H CO2H H OH

H CO2H

OH

HO

OH

HO

Mirror plane (+)-Tartaric acid mp. 174 C

o

Mirror plane (-)-Tartaric acid meso-Tartaric acid mp. 151oC

Enantiomers

Identical!

Diastereomers

Conformation: Ethane
60 H
H H
o

H
H

HH

H H

H
H

Eclipsed H H H H H H H

Staggered

H H H H

Conformation: Ethane
H
H

HH HH

H H

H H

HH

H H

HH

H H

H
H H H

H
H H

H
H

H
H

H
H

H
H

Conformational Analysis

Cyclohexane Bicyclic systems and steroids Heterocyclic systems

Optical activity and Stereoisomerism

Symmetry und chirality

Symmetry axis Cn Symmetry plane Symmetry centre i Rotation/reflection axis Sn

Molecular asymmetry
Chiral axis Chiral plane Chiral centre

Prochirality

Symmetry and Chirality

nFold axis of symmetry Cn

Cl Br I Cl Cl H

Cl

Plane of symmetry
H H H O H H H Cl H

Symmetry and Chirality

Centre of symmetry i
HO i H

O2 H C

C O2 H

OH

n-Fold rotation-reflection axis Sn

OH HO 2C H

H
HO 2C

CO2H
H H OH

OH
OH

OH
CO2H

HO 2C

CO2H

OH

Symmetry and Chirality

Molecules with no reflection symmetry are chiral A molecule with only a Cn axis is chiral

Molecular Asymmetry

Chiral axis Chiral plane Chiral centre

Chiral Axis
a C
n(H2C)

a C

b (CH2)n C C

C C a Allene b a

Alkylidenecycloalkane

Chiral Plane
(CH2)n

H2C

CH2

b c
Br

3 R
1.

2.
3.

Lead atom: atom with highest priority directly linked to the plane Determine the atom sequence in the plane Determine chirality, starting from the lead atom

Chiral Centre
CH3
CH3 Br H

CN

Br H

CN

Prochirality

Enantiotopos Enantiofaces Diastereotopos Diastereofaces

Heterotopy

Homotopic Heterotopic
Constitutopic Stereoheterotopic

Enantiotopic Diastereotopic

Substitution Test

Identical molecules
Homotopic (equivalent)

Isomers
Heterotopic

Constitutional isomers
Constitutopic

Stereoisomers
Stereoheterotopic

Enantiomers
Enantiotopic

Diastereomers
Diastereotopic

Optical Activity and Stereoisomerism

Chiroptical Properties of Chiral Molecules

A linearly polarized wave may be described as the result of a left polarized wave superimposed on a right polarized wave Left and right polarized waves are absorbed differently by an optically active compound When the two components are recombined after passing through an optically active medium, the result is an elliptically polarized wave with ellipticity :

Optical Activity

Optically active compounds are circularly birefringent the refractive indices of the left and right polarized waves differ:
v = c/n , therefore, if vL vR , then nL nR There is a phase difference, resulting in optical rotation: = .d(nL - nR)/ = 180d(nL - nR)/ The optical rotation is dependent on the wavelength Optical rotatory dispersion

Anomalous curve

Chiroptical Properties of Chiral Molecules

Optical rotatory dispersion

Plain curves Anomalous curves

Chiroptical Properties of Chiral Molecules

Optical rotatory dispersion

Achiral chromophores Chiral chromophores

Achiral Chromophores

NO 2 H O CH2

Achiral disturbance

CH3 H NO H CH3
2

Chiral disturbance

O H CH2

Chiral Chromophores
H H

Chiroptical Properties of Chiral Molecules

Optical rotatory dispersion

Constitution Configuration Conformation

Plain Curves

With small amounts of substance, one can measure at shorter wavelengths To determine whether a substance is really optically active and not racemic

Example

N N

NH

CO2H

O MeO OH MeO

N H

Both not active at 589 nm

Inactive Active, [M] = -165o at 365 nm

Racemic

Not racemic

ORD of Steroids: Constitution

Me O

A
B C

Me

Chiroptical Properties of Chiral Molecules

Optical rotatory dispersion

Constitution Configuration and conformation

Cis/trans-Isomerism in Steroids: Configuration

Me OH

Me
O

Me

OH
H

Me

H O H
Me Me OH

H O H

Unsaturated Ketones and Diketones

The Octant Rule for Ketones

5 4 6 3

C 1

Octant Rule

Chiroptical Properties of Chiral Molecules

Octant rule:

Configuration Conformation

Absolute configuration

Summary

Introduction Conformational analysis

Cyclohexane Bicyclic compounds, steroids Heterocyclic compounds

Optical activity and stereoisomerism

Symmetry and chirality Molecular asymmetry Prochirality

Chiroptical properties of chiral molecules

Optical rotatory dispersion

Questions/Remarks ?