Lecture 13 - Stereochemistry

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. CareyThird Edition

Instructor: Rabih O. Al-Kaysi, PhD.

Chapter 7Chapter 7

Stereochemistry Stereochemistry

Lecture 13

7-3Dr. Wolf's CHM 201 & 202

Fischer ProjectionsFischer Projections

• Purpose of Fischer projections is to show Purpose of Fischer projections is to show configuration at chirality center without configuration at chirality center without necessity of drawing wedges and dashes or necessity of drawing wedges and dashes or using models. using models.

7-4Dr. Wolf's CHM 201 & 202

Rules for Fischer projectionsRules for Fischer projectionsRules for Fischer projectionsRules for Fischer projections

Arrange the molecule so that horizontal Arrange the molecule so that horizontal bonds at chirality center point toward you bonds at chirality center point toward you and vertical bonds point away from you.and vertical bonds point away from you.

Br Cl

F

H

7-5Dr. Wolf's CHM 201 & 202


Projection of molecule on page is a cross. When Projection of molecule on page is a cross. When represented this way it is understood that represented this way it is understood that horizontal bonds project outward, vertical bonds horizontal bonds project outward, vertical bonds are back.are back.

Br Cl

F

H

7-6Dr. Wolf's CHM 201 & 202


Projection of molecule on page is a cross. When Projection of molecule on page is a cross. When represented this way it is understood that represented this way it is understood that horizontal bonds project outward, vertical bonds horizontal bonds project outward, vertical bonds are back.are back.

BrBr ClCl

FF

HH

7-7Dr. Wolf's CHM 201 & 202

Physical Properties of Physical Properties of EnantiomersEnantiomers

7-8Dr. Wolf's CHM 201 & 202

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

Different: Different: properties that depend on shape of molecule properties that depend on shape of molecule

(biological-physiological properties) can be(biological-physiological properties) can bedifferent different

Physical properties of enantiomersPhysical properties of enantiomersPhysical properties of enantiomersPhysical properties of enantiomers

7-9Dr. Wolf's CHM 201 & 202

OO OO

CHCH33 CHCH33

HH33CC HH33CCCHCH22 CHCH22

OdorOdorOdorOdor (–)-Carvone(–)-Carvonespearmint oilspearmint oil

(+)-Carvone(+)-Carvonecaraway seed oilcaraway seed oil

S- configuration R- configuration

7-10Dr. Wolf's CHM 201 & 202

IbuprofenIbuprofen is chiral, but normally sold as is chiral, but normally sold asa racemic mixture. The a racemic mixture. The SS enantiomer enantiomer is the one responsible for its analgesic is the one responsible for its analgesic and antiinflammatory properties. and antiinflammatory properties.

Chiral drugsChiral drugsChiral drugsChiral drugs

CHCH22CH(CHCH(CH33))22

HHHH33CC

CC

OO

CC

HOHO

7-11Dr. Wolf's CHM 201 & 202

Reactions That Create A Reactions That Create A

Chiral CenterChiral Center

Many reactions convert achiral Many reactions convert achiral reactants to chiral products.reactants to chiral products.

Many reactions convert achiral Many reactions convert achiral reactants to chiral products.reactants to chiral products.

It is important to recognize, however, that if all of the It is important to recognize, however, that if all of the components of the starting state (reactants, catalysts, components of the starting state (reactants, catalysts, solvents, etc.) are achiral, any chiral product will be solvents, etc.) are achiral, any chiral product will be formed as a racemic mixture.formed as a racemic mixture.

This generalization can be more simply stated as This generalization can be more simply stated as "Optically inactive starting materials can't give "Optically inactive starting materials can't give optically active products."optically active products." (Remember: In order for a (Remember: In order for a substance to be optically active, it must be chiral and one substance to be optically active, it must be chiral and one enantiomer must be present in greater amounts than the enantiomer must be present in greater amounts than the other.other.

ExampleExampleExampleExample

CHCH33CHCH CHCH22

CHCH33COOHCOOH

OO

HH33CC

OO

CHCH22CC

HH

Chiral, but racemicChiral, but racemicAchiralAchiral

50%50%

50%50%

epoxidation from this direction epoxidation from this direction

gives gives RR epoxide epoxide

epoxidation from this direction epoxidation from this direction

gives gives SS epoxide epoxide

RR

SS


CHCH33CHCH CHCH22

Chiral, but racemicChiral, but racemic

BrBr22, H, H22OO

CHCH33CHCHCHCH22BrBr

OHOH

AchiralAchiral


CHCH33CHCH CHCHCHCH33

Chiral, but racemicChiral, but racemic

HBrHBrCHCH33CHCHCHCH22CHCH33

BrBr

AchiralAchiral

7-17Dr. Wolf's CHM 201 & 202

Chiral MoleculesChiral Moleculeswithwith

Two Chirality CentersTwo Chirality Centers

How many stereoisomers when How many stereoisomers when a particular molecule contains a particular molecule contains two chiral centers?two chiral centers?

2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid2,3-Dihydroxybutanoic acid

What are all the possible What are all the possible RR and and SS combinations of combinations of the two chirality centers in this molecule?the two chirality centers in this molecule?

OO

CHCH33CHCHCOHCHCHCOH

HOHO OHOH

2233


What are all the possible What are all the possible RR and and SS combinations of combinations of the two chirality centers in this molecule?the two chirality centers in this molecule?

OO


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


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: diastereomers…….diastereomers…….

similar but not identical chemical and physical propertiessimilar but not identical chemical and physical properties

COCO22HH

CHCH33

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

Fischer projections Fischer projections 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 Fischer projections Fischer projections

COCO22HH

CHCH33

OHOH

OHOH

HH

HH

Erythro and ThreoErythro and ThreoErythro and ThreoErythro and Threo

stereochemical prefixes used to specify stereochemical prefixes used to specify relative relative configuration configuration in molecules with two chirality in molecules with two chirality centerscenters

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

ErythroErythroErythroErythro

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

ThreoThreoThreoThreo

7-30Dr. Wolf's CHM 201 & 202

Achiral MoleculesAchiral Moleculeswithwith

Two Chirality CentersTwo Chirality Centers

It is possible for a molecule to have It is possible for a molecule to have chirality centers yet be achiral.chirality centers yet be achiral.

2,3-Butanediol2,3-Butanediol2,3-Butanediol2,3-Butanediol

Consider a molecule with two equivalently substituted Consider a molecule with two equivalently substituted chirality centers such as 2,3 butanediol.chirality centers such as 2,3 butanediol.

CHCH33CHCHCHCHCHCH33

HOHO OHOH

3322

Three stereoisomers of 2,3-butanediolThree stereoisomers of 2,3-butanediolThree 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 achiral a meso form is an achiral molecule that has molecule that has chirality centerschirality centers


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 achiral a meso form is an achiral molecule that has molecule that has chirality centerschirality centers


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.

HOHO OHOH

HH

HH

HOHO

HH33CC

HH

HHCHCH22CHCH22COCO22HH

CHCH33

HH

CHCH33

11 chirality centers11 chirality centers

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 cholic 2046 are diastereomers of cholic acidacid

Cholic acid Cholic acid Cholic acid Cholic acid

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

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

structural units include chirality centers and cis structural units include chirality centers and cis and/or trans double bondsand/or trans double bonds

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

How many stereoisomers?How many stereoisomers?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?How many stereoisomers?How many stereoisomers? ZZ

A single starting material can give two or moreA single starting material can give two or morestereoisomeric products, but gives one of themstereoisomeric products, but gives one of themin greater amounts than any otherin greater amounts than any other

++

CHCH33

HH

CHCH33

HH

68%68% 32%32%

Stereoselective reactionStereoselective reactionStereoselective reactionStereoselective reaction

CHCH33

CHCH22

HH CHCH33

HH

CHCH33

HH

HH22

PtPt

Chirality CentersChirality CentersOther Than CarbonOther Than Carbon

SiliconSiliconSiliconSilicon

Silicon, like carbon, forms four bonds in its stable Silicon, like carbon, forms four bonds in its stable compounds and many chiral silicon compounds compounds and many chiral silicon compounds have been resolvedhave been resolved

SiSi SiSidd dd

aabb

cc

aabb

cc

Nitrogen in aminesNitrogen in aminesNitrogen in aminesNitrogen in amines

Pyramidal geometry at nitrogen can Pyramidal geometry at nitrogen can produce a chiral structure, but enantiomers produce a chiral structure, but enantiomers equilibrate too rapidly to be resolvedequilibrate too rapidly to be resolved

NN NN:: ::

aabb

cc

aabb

cc

very fastvery fast

Phosphorus in phosphinesPhosphorus in phosphinesPhosphorus in phosphinesPhosphorus in phosphines

Pyramidal geometry at phosphorus can produce a Pyramidal geometry at phosphorus can produce a chiral structure; pyramidal inversion slower than chiral structure; pyramidal inversion slower than for amines and compounds of the type shown have for amines and compounds of the type shown have been resolvedbeen resolved

PP PP:: ::

aabb

cc

aabb

cc

slowslow

Lecture 13 - Stereochemistry

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