23526994 lecture 13 stereo chemistry

8/9/2019 23526994 Lecture 13 Stereo Chemistry

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General

Organic ChemistryTwo credits

Second Semester 2009

King Saud bin Abdulaziz University for Health Science

Reference Book: Organic Chemistry: A Brief Course,

by Robert C. Atkins and Francis A. Carey

Third Edition

Instructor: Rabih O. Al-Kaysi, PhD.


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Chapter 7Chapter 7

StereochemistryStereochemistry

Lecture 13


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Fischer ProjectionsFischer Projections

Purpose ofFischer projections is to showPurpose ofFischer projections is to show

configuration at chirality center withoutconfiguration at chirality center without

necessity of drawing wedges and dashes ornecessity of drawing wedges and dashes or

using models.using models.


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Rules for Fischer projectionsRules for Fischer projections

Arrange the molecule so that horizontalArrange the molecule so that horizontalbonds at chirality centerpoint toward youbonds at chirality centerpoint toward youand vertical bonds point away from you.and vertical bonds point away from you.

Br Cl

F

H


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Projection of molecule on pageis across. WhenProjection of molecule on pageis across. Whenrepresented this way it is understood thatrepresented this way it is understood thathorizontal bonds project outward, vertical bondshorizontal bonds project outward, vertical bonds

are back.are back.

Br Cl

F

H


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Projection of molecule on pageis across. WhenProjection of molecule on pageis across. Whenrepresented this way it is understood thatrepresented this way it is understood thathorizontal bonds project outward, vertical bondshorizontal bonds project outward, vertical bonds

are back.are back.

BrBr ClCl

FF

HH


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Physical Properties ofPhysical Properties ofEnantiomersEnantiomers


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Same:Same:

melting point, boiling point,density, spectroscopy,etc..melting point, boiling point,density, spectroscopy,etc..

Different:Different:

properties that depend on shape of moleculeproperties that depend on shape of molecule

(biological(biological--physiological properties) can bephysiological properties) can be

differentdifferent

Physical properties of enantiomersPhysical properties of enantiomers


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OO OO

CHCH33 CHCH33

HH33CC HH33CCCHCH22 CHCH22

OdorOdor

(())--CarvoneCarvone

spearmint oilspearmint oil

(+)(+)--CarvoneCarvone

caraway seed oilcaraway seed oil

S- configuration R- configuration


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IbuprofenIbuprofen is chiral, but normally soldasis chiral, but normally soldas

aracemic mixture. Thearacemic mixture. TheSSenantiomerenantiomer

is the oneresponsible forits analgesicis the oneresponsible forits analgesic

andantiinflammatory properties.andantiinflammatory properties.

ChiraldrugsChiraldrugs

CHCH22CH(CHCH(CH33))22

HHHH33CC

CC

OO

CC

HOHO


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Reactions That CreateAReactions That CreateAChiral CenterChiral Center


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Many reactions convert achiralMany reactions convert achiral

reactants to chiral products.reactants to chiral products.

It is important to recognize, however, that ifall of theIt is important to recognize, however, that ifall of thecomponents of the starting state (reactants,catalysts,components of the starting state (reactants,catalysts,solvents,etc.) areachiral,any chiral product will besolvents,etc.) areachiral,any chiral product will be

formedas aracemic mixture.formedas aracemic mixture.

This generalizationcan be more simply statedasThis generalizationcan be more simply statedas"Optically inactive starting materials can't give"Optically inactive starting materials can't giveoptically active products."optically active products." (Remember: In orderfora(Remember: In orderforasubstance to be optically active,it must bechiral and onesubstance to be optically active,it must bechiral and oneenantiomermust be present ingreateramounts than theenantiomermust be present ingreateramounts than theother.other.


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ExampleExample

CHCH33CHCH CHCH22

CHCH33COOHCOOH

OO

HH33CC

OO

CHCH22CC

HH

Chiral, but racemicChiral, but racemicAchiralAchiral


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50%50%

50%50%

epoxidation from this directionepoxidation from this direction

givesgives RR epoxideepoxide

epoxidation from this directionepoxidation from this direction

givesgives SS epoxideepoxide

RR

SS


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ExampleExample

CHCH33CHCH CHCH22

Chiral, but racemicChiral, but racemic

BrBr22, H, H22OO

CHCH33CHCHCHCH22BrBr

OHOH

AchiralAchiral


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ExampleExample

CHCH33CHCH CHCHCHCH33

Chiral, but racemicChiral, but racemic

HBrHBr

CHCH33CHCHCHCH22CHCH33

BrBr

AchiralAchiral


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Chiral MoleculesChiral Molecules

withwithTwo Chirality CentersTwo Chirality Centers

How many stereoisomers whenHow many stereoisomers whena particularmoleculecontainsa particularmoleculecontainstwo chiral centers?two chiral centers?


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2,32,3--Dihydroxybutanoic acidDihydroxybutanoic acid

What areall the possibleWhat areall the possibleRR andandSScombinations ofcombinations of

the two chirality centers in this molecule?the two chirality centers in this molecule?

OO

CHCH33CHCHCOHCHCHCOH

HOHO OHOH

2233


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What areall the possibleWhat areall the possibleRR andandSScombinations ofcombinations of

the two chirality centers in this molecule?the two chirality centers in this molecule?

OO


HOHO OHOH

2233

CarbonCarbon--22 RR RR SS SS

CarbonCarbon--33 RR SS RR SS


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4 Combinations = 4Stereoisomers4 Combinations = 4Stereoisomers

OO


HOHO OHOH

2233




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4 Combinations = 4Stereoisomers4 Combinations = 4Stereoisomers

What is therelationship between these stereoisomers?What is therelationship between these stereoisomers?

OO


HOHO OHOH

2233




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OO


HOHO OHOH

2233



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

22RR,3,3SS and 2and 2SS,3,3RR


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OO


HOHO OHOH

2233



but not all relationships are enantiomericbut not all relationships are enantiomeric

stereoisomers that arenot enantiomers are:stereoisomers that arenot enantiomers are:

diastereomers.diastereomers.similarbut not identical chemical and physical propertiessimilarbut not identical chemical and physical properties


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COCO22HH

CHCH33

FischerProjectionsFischerProjections

recall forFischerrecall forFischer

projection: horizontalprojection: horizontal

bonds point towardbonds point toward

you; vertical bondsyou; vertical bondspoint awaypoint away

staggeredconformationstaggeredconformation

does not havecorrectdoes not havecorrectorientation of bonds fororientation of bonds for

FischerprojectionFischerprojection


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Fischer projectionsFischer projections

transformtransform

molecule tomolecule to

eclipsedeclipsedconformationconformation

in ordertoin orderto

constructconstruct

FischerFischerprojectionprojection


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Fischer projectionsFischer projections

COCO22HH

CHCH33

OHOH

OHOH

HH

HH


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Erythro andThreoErythro andThreo

stereochemical prefixes used to specifystereochemical prefixes used to specify relativerelative

configurationconfigurationin molecules with two chiralityin molecules with two chirality

centerscenters

easiest to apply using Fischerprojectionseasiest to apply using Fischerprojections

orientation: vertical carbonchainorientation: vertical carbonchain


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whencarbonchainis vertical, same (orwhencarbonchainis vertical, same (or

analogous) substituents onanalogous) substituents on same sidesame side ofof


COCO22HH

CHCH33

OHOH

OHOH

HH

HH

9.59.5 +9.5+9.5

COCO22HH

CHCH33

HH

HH

HOHO

HOHO

ErythroErythro


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whencarbonchainis vertical, same (orwhencarbonchainis vertical, same (or

analogous) substituents onanalogous) substituents on opposite sidesopposite sides ofof


+17.8+17.8 17.817.8

OHOH

COCO22HH

CHCH33

HH

HH

HOHO

COCO22HH

CHCH33

OHOHHH

HHHOHO

ThreoThreo


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Achiral MoleculesAchiral Molecules

withwithTwo Chirality CentersTwo Chirality Centers

It is possible fora molecule to haveIt is possible fora molecule to havechirality centers yet beachiral.chirality centers yet beachiral.


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2,32,3--ButanediolButanediol

Considera molecule with two equivalently substitutedConsidera molecule with two equivalently substituted

chirality centers such as 2,3 butanediol.chirality centers such as 2,3 butanediol.

CHCH33CHCHCHCHCHCH

33

HOHO OHOH

3322


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Three stereoisomers of2,3Three stereoisomers of2,3--butanediolbutanediol

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

chiralchiral chiralchiral achiralachiral


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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


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

chiralchiral chiralchiral

these two arethese two are

enantiomersenantiomers


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

chiralchiral chiralchiral

CHCH33

CHCH33

OHOHHH

HHHOHOHH OHOH

CHCH33

CHCH33

HHHOHOthese two arethese two are

enantiomersenantiomers


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22RR,3,3SS

achiralachiral

the third structure isthe third structure issuperposable on itssuperposable on its

mirror imagemirror image


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22RR,3,3SS

achiralachiral

therefore, this structuretherefore, this structure

andits mirrorimageandits mirrorimage

are the sameare the same

it is calleda meso formit is calleda meso form

a meso form is anachirala meso form is anachiral

molecule that has chiralitymolecule that has chirality

centerscenters


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22RR,3,3SS

achiralachiral

HH

CHCH33

CHCH33

OHOH

OHOHHHHHHOHO

CHCH33

CHCH33

HHHOHO

therefore, this structuretherefore, this structure

andits mirrorimageandits mirrorimage

are the sameare the same

it is calleda meso formit is calleda meso form

a meso form is anachirala meso form is anachiral

molecule that has chiralitymolecule that has chirality

centerscenters


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22RR,3,3SS

achiralachiral

meso forms havea plane ofmeso forms havea plane of

symmetry and/oracenterofsymmetry and/oracenterof

symmetrysymmetry

plane of symmetry is mostplane of symmetry is most

commoncasecommoncase

top half of moleculeis mirrortop half of moleculeis mirror

image of bottom halfimage of bottom half


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22RR,3,3SS

achiralachiral

HH

CHCH33

CHCH33

OHOH

OHOHHHHHHOHO

CHCH33

CHCH33

HHHOHO

A line drawnA line drawn

the center ofthe center of

the Fischerthe Fischerprojection of aprojection of a

meso formmeso form

bisects it intobisects it into

two mirrortwo mirror--image halves.image halves.


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HOHO OHOH

HH

HH

HOHO

HH33CC

HH

HH

CHCH22CHCH22COCO22HHCH

CH33

HH

CHCH33

11 chirality centers11 chirality centers

221111 = 2048 stereoisomers= 2048 stereoisomers

oneis "natural" cholicacidoneis "natural" cholicacid

a secondis theenantiomerofa secondis theenantiomerof

natural cholicacidnatural cholicacid

2046arediastereomers ofcholic2046arediastereomers ofcholic

acidacid

Cholic acidCholic acid


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maximummaximum numberof stereoisomers = 2numberof stereoisomers = 2nn

wherewherenn = numberof structural units capable of= numberof structural units capable of

stereochemical variationstereochemical variation

structural units includechirality centers andcisstructural units includechirality centers andcis

and/ortrans double bondsand/ortrans double bonds

numberis reduced to less than 2numberis reduced to less than 2nn if meso formsif meso forms

are possibleare possible

How many stereoisomers?How many stereoisomers?


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33--PentenPenten--22--olol

HOHO HH

EE RR

HH OHOH

EE SS

HHHOHO

ZZ RR

HH OHOH

SS

How many stereoisomers?How many stereoisomers?

ZZ


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A single starting material cangive two ormoreA single starting material cangive two ormore

stereoisomeric products, but gives one of themstereoisomeric products, but gives one of them

ingreateramounts thanany otheringreateramounts thanany other

++

CHCH33

HH

CHCH33

HH

68%68% 32%32%

Stereoselective reactionStereoselective reaction

CHCH33

CHCH22

HH

CHCH33

HH

CHCH33

HH

HH22

PtPt


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Chirality CentersChirality CentersOther Than CarbonOther Than Carbon


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SiliconSilicon

Silicon, likecarbon, forms fourbonds inits stableSilicon, likecarbon, forms fourbonds inits stablecompounds and many chiral siliconcompoundscompounds and many chiral siliconcompounds

have beenresolvedhave beenresolved

SiSi SiSidd dd

aa

bb

cc

aa

bb

cc


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Nitrogen in aminesNitrogen in amines

Pyramidal geometry at nitrogencan producePyramidal geometry at nitrogencan produceachiral structure, but enantiomersachiral structure, but enantiomersequilibrate too rapidly to beresolvedequilibrate too rapidly to beresolved

NN NN:: ::

aa

bb

cc

aa

bb

cc

very fastvery fast


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Phosphorus in phosphinesPhosphorus in phosphines

Pyramidal geometry at phosphorus can produceaPyramidal geometry at phosphorus can producea

chiral structure; pyramidal inversion slowerthanchiral structure; pyramidal inversion slowerthan

foramines andcompounds of the type shown haveforamines andcompounds of the type shown have

beenresolvedbeenresolved

PP PP:: ::

aa

bb

cc

aa

bb

cc

slowslow

23526994 lecture 13 stereo chemistry

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