The word chiral derives from the Greek word ceir (cheir), meaning hand. Our hands are chiral - the...

The word chiral derives from the Greek word ceir (cheir), meaning hand.

Our hands are chiral - the right hand is a mirror image of the left -

as are most of life's molecules such as (R)-alanine and (S)-alanine,

which are mirror images of each other.

OPTICAL ISOMERISM DEALS WITH CHIRALITY

NOT ALL OBJECTS EXHIBIT CHIRALITY, BUT MOST OBJECTS** HAVE MIRROR IMAGES.

EXCEPTIONS ARE: VAMPIRES,THE DEVIL, FALLEN MEN

OPTICAL ISOMERISM

FAUST GOUNOD

HOFFMAN (TALES OF HOFFMAN) HAD HIS REFLECTION STOLEN BY ANTONIO WHO GAVE IT TO DAPERTULU (ASORCEROR).

Alone in his study, the aged Dr. Faust despairs that his lifelong search for a solution to the riddle of life has been in vain. Twice he raises a goblet of

poison to his lips but falters when the songs of young men and women outside his window re-awaken the unfulfilled passions and desires of his youth. Cursing life and human passion, the envious philosopher calls on Satan for help. The Devil appears, and Faust tells him of his longing for

youth and pleasure; Méphistophélès replies that these desires can be realized if he will forfeit his soul. Faust hesitates until the Devil conjures up a vision of a lovely maiden, Marguerite. A magic potion transforms

Faust into a handsome youth, and he leaves with Méphistophélès in search of Marguerite (Duet: "A moi les plaisirs").

SO HOW ONE DISTINGUISHED MOLECULES THAT EXHIBIT CHIRALITY AND MOLECULES THAT LACK CHIRALITY (CALLED ACHIRAL MOLECULES)?

MIRROR IMAGES OF CHIRAL MOLECULES ARE NON-SUPERPOSABLE (THAT IS THEY ARE DIFFERENT)

MIRROR IMAGES OF A CHIRAL MOLECULES ARE SUPERPOSABLE (THAT IS THEY ARE THE SAME)

CHIRAL OBJECTS: FEET, SCREWS, GOLF CLUBS, STUDENTS ARM CHAIRS, ENGLISH AND AMERICAN CARS

ACHIRAL OBJECTS: SPOONS, KNIVES, FORKS

Alice’s father was Dean of Christ Church, Oxford

Mathematic Don at Christ Church, Oxford University

Amateur Photographer

Real name was Charles Dodgson

Alice and Lewis Carroll

WHAT DO CHIRAL MOLECULES LACK THAT ACHIRAL HAVE?

CHIRAL MOLECULES LACK SYMMETRY

A CHIRAL MOLECULES POSSESS SYMMETRY

A symmetry element is a plane, a line or a point in or through an object, about which a rotation or reflection leaves the object in an orientation indistinguishable from the original.

CONSIDER 1,2-DIMETHYLCYCLOPENTANE

Me Me Me Me

SAME, thus achiral

each has a plane of symmetry

Me

Me

Me

Me

different mirror images

ASYMMETRIC CARBON ATOM (CHIRALITY CENTER) OR (STEREOCENTER)

MOLECULE THAT HAS ONE OF THE ABOVE WILL BE CHIRAL

THAT IS, LACKS SYMMETRY

REQUIREMENT: 4 DIFFERENT GROUPS

A

D BC

A

CB D

BD

A

C

DB

A

C

NOTE: EXCHANGE ANY TWO GROUPS TO GO FROM ENANTIOMERTO THE OTHER ENANIOMER!!

EXAMPLES

H3C H

OMe

OH

O

H NH2 CHO

CH2OH

H OH

Cl OMeO

Me

O

Me

(R), (S) Nomenclature

• Different molecules (enantiomers) must have different names.

C

CO OH

H3CNH2

H

natural alanine=>

•Usually only one enantiomer will be biologically active.

•Configuration around the chiral carbon is specified with (R) and (S).

Cahn-Ingold-Prelog Rules Overview

Assign priorities to each group

View molecule with the lowestpriority away from the viewer

Arrow is drawn from the atom with 1st priority through the atom with 2nd priority to the atom with 3rd priority.

If arrow points clockwise - R(rectus)

If arrow points counter- clockwise - S (sinister)

Assigning priorities-CASE 1

• Assign a priority number to each atom attached to the chiral carbon.

•Atom with highest atomic number assigned the highest priorities #1.

In case of isotopes, high(er)est priority given tothe isotope with high(er)est mass number.

CASE 1 - four different atoms attached to chiral atom

3-D Examples Assigning PrioritiesCl

F BrH 1

2

3

4

Cl

FBr H

1

2

34

PERSPECTIVE

BrF

Cl

H

FBr

Cl

H

WEDGE1

2

3

4

1

2

3

4

F Br

H

Cl

F Br

H

Cl

FISHER

PRIORITY ASSIGNMENT EXAMPLES CASE 2 - In case of ties among 1st atom, go to 2nd

atoms, then to 3rd etc until the tie is broken.Consider straight chain groups

Me < Et<n-propyl etcConsider effect of branching

Et< isopropyl < tert-butyl

Consider effect of hetero atom

Tert-butyl < CH2OMe

Groups possessing multiple bonds

C=C C-C

C C Carbon doubly bondedto carbon is likened unto a carbon bonded to two carbons

Assign Priorities

C

CO OH

H3CNH2

H

natural alanine

1

2

3 4

Cl

HCl

H

*

12

34

12

3

4

=>

CC

O

H

CH CH2

CH2OHCH(CH3)2

*C

C

C

CH2OHCH(CH3)2

HO

O

C

CH CH2

C

*expands to

Assign (R) or (S)• Working in 3D, rotate molecule so that lowest

priority group is in back.• Draw an arrow from highest to lowest priority

group.• Clockwise = (R), Counterclockwise = (S)

=>

Examples

Fischer Projections• Flat drawing that represents a 3D molecule

• A chiral carbon is at the intersection of horizontal and vertical lines.

• Horizontal lines are forward, out-of-plane.

• Vertical lines are behind the plane.

Fischer Rules

• Carbon chain is on the vertical line.

• Highest oxidized carbon at top.

• Rotation of 180 in plane doesn’t change molecule.

• Do not rotate 90!• Do not turn over out of plane! =>

Fischer Mirror Images

• Easy to draw, easy to find enantiomers, easy to find internal mirror planes.

• Examples:CH3

H Cl

Cl H

CH3

CH3

Cl H

H Cl

CH3

CH3

H Cl

H Cl

CH3=>

Fischer (R) and (S)• Lowest priority (usually H) comes forward, so assignment

rules are backwards!

• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).

• Example:

CH3

H Cl

Cl H

CH3

(S)

(S) =>

Properties of Enantiomers• Same boiling point, melting point, density• Same refractive index• Different direction of rotation in polarimeter• Different interaction with other chiral molecules

– Enzymes– Taste buds, scent

=>

Optical Activity• Rotation of plane-polarized light• Enantiomers rotate light in opposite directions, but

same number of degrees.

=>

Polarimetry• Use monochromatic light, usually sodium D

• Movable polarizing filter to measure angle

• Clockwise = dextrorotatory = d or (+)

• Counterclockwise = levorotatory = l or (-)

• Not related to (R) and (S)

=>

Biological Discrimination

=>

Racemic Mixtures

• Equal quantities of d- and l- enantiomers.

• Notation: (d,l) or ()

• No optical activity.

• The mixture may have different b.p. and m.p. from the enantiomers!

=>

Racemic Products

If optically inactive reagents combine to form a chiral molecule, a racemic mixture of enantiomers is formed.

=>

Chirality of Conformers

• If equilibrium exists between two chiral conformers, molecule is not chiral.

• Judge chirality by looking at the most symmetrical conformer.

• Cyclohexane can be considered to be planar, on average.

=>

Mobile Conformers

H

BrH

Br

H

BrH

Br

Nonsuperimposable mirror images,but equal energy and interconvertible.

BrBr

H H

Use planarapproximation.

=>

Nonmobile ConformersIf the conformer is sterically hindered, it may

exist as enantiomers.

=>

Allenes• Chiral compounds with no chiral carbon

• Contains sp hybridized carbon with adjacent double bonds: -C=C=C-

• End carbons must have different groups.

Allene is achiral.=>

Fischer Projections• Flat drawing that represents a 3D molecule

• A chiral carbon is at the intersection of horizontal and vertical lines.

• Horizontal lines are forward, out-of-plane.

• Vertical lines are behind the plane.

Fischer Rules

• Carbon chain is on the vertical line.

• Highest oxidized carbon at top.

• Rotation of 180 in plane doesn’t change molecule.

• Do not rotate 90!• Do not turn over out of plane! =>

Fischer Mirror Images

• Easy to draw, easy to find enantiomers, easy to find internal mirror planes.

• Examples:CH3

H Cl

Cl H

CH3

CH3

Cl H

H Cl

CH3

CH3

H Cl

H Cl

CH3=>

Fischer (R) and (S)• Lowest priority (usually H) comes forward, so assignment

rules are backwards!

• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).

• Example:

CH3

H Cl

Cl H

CH3

(S)

(S) =>

Diastereomers

• Stereoisomers that are not mirror images.

• Geometric isomers (cis-trans)

• Molecules with 2 or more chiral carbons. =>

Alkenes

Cis-trans isomers are not mirror images, so these are diastereomers.

C CH H

CH3H3C

cis-2-butene trans-2-butene

C CH

H3C

CH3

H =>

Ring Compounds

• Cis-trans isomers possible.

• May also have enantiomers.

• Example: trans-1,3-dimethylcylohexane

CH3

H

H

CH3

CH3

H

H

CH3

=>

Two or More Chiral Carbons• Enantiomer? Diastereomer? Meso? Assign (R) or (S) to

each chiral carbon.

• Enantiomers have opposite configurations at each corresponding chiral carbon.

• Diastereomers have some matching, some opposite configurations.

• Meso compounds have internal mirror plane.

• Maximum number is 2n, where n = the number of chiral carbons. =>

ExamplesCOOH

H OH

HO H

COOH

(2R,3R)-tartaric acid

COOH

COOH

HO H

H OH

(2S,3S)-tartaric acid

=> (2R,3S)-tartaric acid

COOH

COOH

H OH

H OH

Fischer-Rosanoff Convention• Before 1951, only relative configurations could be known.

• Sugars and amino acids with same relative configuration as (+)-glyceraldehyde were assigned D and same as (-)-glyceraldehyde were assigned L.

• With X-ray crystallography, now know absolute configurations: D is (R) and L is (S).

• No relationship to dextro- or levorotatory. =>

D and L Assignments

CHO

H OH

CH2OH

D-(+)-glyceraldehyde

*CHO

H OH

HO H

H OH

H OH

CH2OHD-(+)-glucose

*

COOH

H2N H

CH2CH2COOH

L-(+)-glutamic acid

*=>

Properties of Diastereomers

• Diastereomers have different physical properties: m.p., b.p.

• They can be separated easily.• Enantiomers differ only in reaction with

other chiral molecules and the direction in which polarized light is rotated.

• Enantiomers are difficult to separate. =>

Resolution of Enantiomers

React a racemic mixture with a chiral compound to form diastereomers, which can be separated.

=>

ChromatographicResolution of Enantiomers

=>

End of Chapter 5