molecules with more than one chiral carbon

Molecules with more than OneMolecules with more than One

Chiral CarbonChiral Carbon

2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid

What are all the possible What are all the possible RR and and SS combinations of the two chiral carbons in this combinations of the two chiral carbons in this molecule?molecule?

OO

CHCH33CHCHCOHCHCHCOH

HOHO OHOH

2233

Carbon-2Carbon-2 RR RR SS SSCarbon-3Carbon-3 RR SS RR SS


4 Combinations = 4 Stereoisomers4 Combinations = 4 Stereoisomers

OO


HOHO OHOH

2233



4 Combinations = 4 Stereoisomers4 Combinations = 4 Stereoisomers

What is the relationship between these stereoisomers?What is the relationship between these stereoisomers?

OO


HOHO OHOH

2233



OO


HOHO OHOH

2233


enantiomers:enantiomers: 22RR,3,3RR and 2 and 2SS,3,3SS22RR,3,3SS and 2 and 2SS,3,3RR

They have the same physical properties.They have the same physical properties.

HOHO

COCO22HH

CHCH33

HH

OHOHHHRR

RR

COCO22HH

CHCH33

HH

HHHOHO

OHOH

SS

SS

enantiomersenantiomersenantiomersenantiomers

COCO22HH

HH

CHCH33

HOHO

HHHOHO

RR

SS

COCO22HH

CHCH33

HH OHOH

OHOHHHRR

SS


[[] = -9.5°] = -9.5° [[] = +9.5°] = +9.5°

[[] = -17.8°] = -17.8°[[] = +17.8°] = +17.8°


OO


HOHO OHOH

2233


but not all relationships are enantiomericbut not all relationships are enantiomeric

stereoisomers that are not enantiomers are stereoisomers that are not enantiomers are diastereomersdiastereomers

IsomersIsomers

stereoisomersstereoisomersconstitutionalconstitutionalisomersisomers

diastereomersdiastereomersenantiomersenantiomers

HOHO

COCO22HH

CHCH33

HH

OHOHHHRR

RR

COCO22HH

CHCH33

HH

HHHOHO

OHOH

SS

SS


COCO22HH

HH

CHCH33

HOHO

HHHOHO

RR

SS

diastereomersdiastereomersdiastereomersdiastereomers

COCO22HH

CHCH33

HH OHOH

OHOHHHRR

SS


[[] = -9.5°] = -9.5° [[] = +9.5°] = +9.5°

[[] = -17.8°] = -17.8°[[] = +17.8°] = +17.8°

COCO22HH

CHCH33

Fischer ProjectionsFischer Projections

recall for Fischer recall for Fischer projection: horizontal projection: horizontal bonds point toward bonds point toward you; vertical bonds you; vertical bonds point away point away

staggered staggered conformation does conformation does not have correct not have correct orientation of bonds orientation of bonds for Fischer projectionfor Fischer projection

Fischer projections Fischer projections

transform transform molecule to molecule to eclipsed eclipsed conformation conformation in order to in order to construct construct Fischer Fischer projectionprojection

Fischer projections Fischer projections

COCO22HH

CHCH33

OHOH

OHOH

HH

HH

Erythro and ThreoErythro and Threo

stereochemical prefixes used to specify stereochemical prefixes used to specify relative configuration relative configuration in molecules with two in molecules with two chiral carbonschiral carbons

easiest to apply using Fischer projectionseasiest to apply using Fischer projections

orientation: vertical carbon chainorientation: vertical carbon chain

when carbon chain is vertical, same (or when carbon chain is vertical, same (or analogous) substituents on analogous) substituents on same sidesame side of of Fischer projectionFischer projection

COCO22HH

CHCH33

OHOH

OHOH

HH

HH

––9.5°9.5° +9.5°+9.5°

COCO22HH

CHCH33

HH

HH

HOHO

HOHO

ErythroErythro

when carbon chain is vertical, same (or when carbon chain is vertical, same (or analogous) substituents on analogous) substituents on opposite sidesopposite sides of of Fischer projectionFischer projection

+17.8°+17.8° ––17.8°17.8°

OHOH

COCO22HH

CHCH33

HH

HH

HOHO

COCO22HH

CHCH33

OHOHHH

HHHOHO

ThreoThreo

Perspective formula

Fischer projection

Achiral MoleculesAchiral Moleculeswithwith

Two Chiral CentersTwo Chiral Centers

It is possible for a molecule to It is possible for a molecule to have chiral carbons yet be have chiral carbons yet be achiral.achiral.

Symmetry Tests Symmetry Tests

for Chiralityfor Chirality

Any molecule with a plane of symmetryAny molecule with a plane of symmetryor a center of symmetry must be or a center of symmetry must be achiralachiral..

A plane of symmetry bisects a molecule into two A plane of symmetry bisects a molecule into two mirror image halves. Chlorodifluoromethane mirror image halves. Chlorodifluoromethane

has a plane of symmetry.has a plane of symmetry.

Plane of symmetryPlane of symmetry

A plane of symmetry bisects a molecule into two A plane of symmetry bisects a molecule into two mirror image halves.mirror image halves.

1-Bromo-1-chloro-2-fluoroethene has a plane1-Bromo-1-chloro-2-fluoroethene has a planeof symmetry.of symmetry.

Plane of symmetryPlane of symmetry

A point in the center of theA point in the center of the

molecule is a center of molecule is a center of

symmetry if a line drawn symmetry if a line drawn

from it to some element, from it to some element,

when extended an equal when extended an equal

distance in the opposite distance in the opposite

direction, encounters an direction, encounters an

identical element. identical element.

Center of symmetryCenter of symmetry

A point in the center of theA point in the center of the

molecule is a center of molecule is a center of

symmetry if a line drawn symmetry if a line drawn

from it to any element, from it to any element,

when extended an equal when extended an equal

distance in the opposite distance in the opposite

direction, encounters an direction, encounters an

identical element. identical element.

Center of symmetryCenter of symmetry

2,3-Butanediol2,3-Butanediol

Consider a molecule with two equivalently Consider a molecule with two equivalently substituted chiral carbons such as 2,3-substituted chiral carbons such as 2,3-butanediol.butanediol.

CHCH33CHCHCHCHCHCH33

HOHO OHOH

3322

Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediol

22RR,3,3RR 22SS,3,3SS 22RR,3,3SS

chiralchiral chiralchiral achiralachiral


22RR,3,3RR 22SS,3,3SS 22RR,3,3SS

chiralchiral chiralchiral achiralachiral

CHCH33

CHCH33

OHOHHH

HHHOHOHH OHOH

CHCH33

CHCH33

HHHOHO HH

CHCH33

CHCH33

OHOH

OHOHHH


22RR,3,3RR 22SS,3,3SS

chiralchiral chiralchiral

these two arethese two areenantiomersenantiomers


22RR,3,3RR 22SS,3,3SS

chiralchiral chiralchiral

CHCH33

CHCH33

OHOHHH

HHHOHOHH OHOH

CHCH33

CHCH33

HHHOHOthese two arethese two areenantiomersenantiomers


22RR,3,3SS

achiralachiral

the third structure is the third structure is superposable on itssuperposable on itsmirror imagemirror image


22RR,3,3SS

achiralachiral

therefore, this structure therefore, this structure and its mirror imageand its mirror imageare the same are the same

it is called a meso formit is called a meso form

a meso form is an a meso form is an achiral molecule that achiral molecule that has chiral carbonshas chiral carbons


22RR,3,3SS

achiralachiral

HH

CHCH33

CHCH33

OHOH

OHOHHHHHHOHO

CHCH33

CHCH33

HHHOHO

therefore, this structure therefore, this structure and its mirror image and its mirror image are the same are the same

it is called a meso formit is called a meso form

a meso form is an a meso form is an achiral molecule that achiral molecule that has chiral carbonshas chiral carbons


22RR,3,3SS

achiralachiral

meso forms have a plane of meso forms have a plane of symmetry and/or a center of symmetry and/or a center of symmetrysymmetry

plane of symmetry is most plane of symmetry is most common casecommon case

top half of molecule is mirror top half of molecule is mirror image of bottom halfimage of bottom half


22RR,3,3SS

achiralachiral

HH

CHCH33

CHCH33

OHOH

OHOHHHHHHOHO

CHCH33

CHCH33

HHHOHO

A line drawnA line drawnthe center ofthe center ofthe Fischer the Fischer projection of aprojection of ameso formmeso formbisects it intobisects it intotwo mirror-two mirror-image halves.image halves.

SS RR RRRR

chiralchiralmesomeso

There are three stereoisomers of 1,2-dichloro-There are three stereoisomers of 1,2-dichloro-

cyclopropane; the achiral (meso) cis isomer cyclopropane; the achiral (meso) cis isomer

and two enantiomers of the trans isomer.and two enantiomers of the trans isomer.

Cyclic compoundsCyclic compounds

Chirality:di-substituted cyclopentanes

andcylcohexanes

1,2-Disubstituted Cyclopentanes

CH3CH3CH3

CH3

meso

R-

S-

R-

R-

No plane of symmetry

1,3-Disubstituted Cylcopentanes

CH3 CH3CH3

CH3

meso

R- S- R- R-

No plane of symmetry

As long as any one conformer of a compound has a plane of symmetry, the compound will be achiral

plane ofsymmetry

plane ofsymmetry

Cyclohexane StereochemistryCis isomers

CH3CH3

CH3

CH3CH3

CH3

1,2-disubstituted-cis-cyclohexaneStereochemistry

CH3

CH3

CH3

CH3

CH3

CH3

Mirror

Same

(Rotate to See)

Cyclohexane StereochemistryTrans isomers

CH3

CH3CH3

CH3 CH3

CH3

No Plane of Symmetry No plane of symmetry

Plane of Symmetry

CH3CH3

Point

..

MoleculesMolecules

withwith

Multiple chiral carbonsMultiple chiral carbons

maximummaximum number of stereoisomers = 2 number of stereoisomers = 2nn

where where nn = number of structural units = number of structural units capable of stereochemical variationcapable of stereochemical variation

structural units include chiral carbons and structural units include chiral carbons and cis and/or trans double bondscis and/or trans double bonds

number is reduced to less than 2number is reduced to less than 2nn if meso if meso forms are possibleforms are possible

How many stereoisomers?How many stereoisomers?

ExampleExample

4 chiral carbons4 chiral carbons

16 stereoisomers16 stereoisomers

OO

HOCHHOCH22CCH—H—CCH—H—CCH—H—CCHCHHCH

OHOH OHOH OHOH OHOH

Hexaldose sugarHexaldose sugar

HOHO OHOH

HH

HH

HOHO

HH33CC

HH

HHCHCH22CHCH22COCO22HH

CHCH33

HH

CHCH33

11 chiral carbons11 chiral carbons

221111 = 2048 stereoisomers = 2048 stereoisomers

one is "natural" cholic acidone is "natural" cholic acid

a second is the enantiomer of a second is the enantiomer of natural cholic acidnatural cholic acid

2046 are diastereomers of 2046 are diastereomers of cholic acidcholic acid

Cholic acidCholic acid

maximummaximum number of stereoisomers = 2 number of stereoisomers = 2nn

where where nn = number of structural units = number of structural units capable of stereochemical variationcapable of stereochemical variation

structural units include chiral carbons and structural units include chiral carbons and cis and/or trans double bondscis and/or trans double bonds

number is reduced to less than 2number is reduced to less than 2nn if meso if meso forms are possibleforms are possible

How many stereoisomers?How many stereoisomers?

3-Penten-2-ol3-Penten-2-ol

HOHO HH

EE RR

HH OHOH

EE SS

HHHOHO

ZZ RR

HH OHOH

SS

How many stereoisomers?How many stereoisomers? ZZ

Ch05-diastereomer

• 28-02-2009

app.eng.ubu.ac.th/~edocs/f20090829Sompop32.pdf

molecules with more than one chiral carbon

Documents

symmetry tests

center of symmetrya

fischer projectionsrecall

fischer projection9

mirror image halves

vertical bonds

s combinations

chiral carbons easiest