dr. wolf's chm 201 & 202 7-1 chapter 7 stereochemistry

Dr. Wolf's CHM 201 & 202 7-1

Chapter 7Stereochemistry

Dr. Wolf's CHM 201 & 202 7-2

Molecular Chirality: Molecular Chirality: EnantiomersEnantiomers

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

A molecule is A molecule is chiralchiral if its two mirror image if its two mirror image forms forms are notare not superposable upon one another. superposable upon one another. ASYMMETRIC!ASYMMETRIC!

A molecule is A molecule is achiralachiral if its two mirror image if its two mirror image forms forms areare superposable. SYMMETRIC! superposable. SYMMETRIC!

ChiralityChiralityChiralityChirality

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

BrBrClCl

HH

FF

Bromochlorofluoromethane is chiralBromochlorofluoromethane is chiralBromochlorofluoromethane is chiralBromochlorofluoromethane is chiral

It cannot be It cannot be superposed point superposed point for point on its for point on its mirror image.mirror image.

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

BrBrClCl

HH

FF


HH

ClClBrBr

FFTo show To show nonsuperposability, rotate nonsuperposability, rotate this model 180° around a this model 180° around a vertical axis.vertical axis.

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

BrBrClCl

HH

FF


HH

ClClBrBr

FF

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

Another lookAnother lookAnother lookAnother look

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

are enantiomers with respect to each otherare enantiomers with respect to each other

andand

nonsuperposable mirror images are nonsuperposable mirror images are called enantiomerscalled enantiomers

EnantiomersEnantiomersEnantiomersEnantiomers

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

IsomersIsomersIsomersIsomers

stereoisomersstereoisomersconstitutionalconstitutionalisomersisomers

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



diastereomersdiastereomersenantiomersenantiomers

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

ChlorodifluoromethaneChlorodifluoromethane

is is achiralachiral



Dr. Wolf's CHM 201 & 202 7-12





The two The two structures are structures are mirror images, mirror images, but are not but are not enantiomers, enantiomers, because they because they can be can be superposed on superposed on each other.each other.

Dr. Wolf's CHM 201 & 202 7-13

The Chirality CenterThe Chirality Center

Dr. Wolf's CHM 201 & 202 7-14

a carbon atom with foura carbon atom with fourdifferent groups attached to itdifferent groups attached to it

also called:also called:chiral centerchiral centerasymmetric centerasymmetric centerstereocenterstereocenterstereogenic centerstereogenic center

The Chirality CenterThe Chirality Center

ww

xx yy

zz

CC

Dr. Wolf's CHM 201 & 202 7-15

A molecule with a single chirality center A molecule with a single chirality center is chiral.is chiral.

BromoBromochlorochlorofluorofluoromethanemethane is an example. is an example.

Chirality and chirality centersChirality and chirality centers

ClCl FF

BrBr

HH

CC

Dr. Wolf's CHM 201 & 202 7-16

A molecule with a single chirality center A molecule with a single chirality center is chiral.is chiral.

2-Butanol is another example.2-Butanol is another example.

Chirality and chirality centersChirality and chirality centers

CHCH33

OHOH

HH

CC CHCH22CHCH33

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

Examples of molecules with 1 chirality centerExamples of molecules with 1 chirality center

CHCH33

CC

CHCH22CHCH33

CHCH22CHCH22CHCH22CHCH33CHCH33CHCH22CHCH22

a chiral alkanea chiral alkane

Dr. Wolf's CHM 201 & 202 7-18


Linalool, a naturally occurring chiral alcoholLinalool, a naturally occurring chiral alcohol

OHOH

Dr. Wolf's CHM 201 & 202 7-19


1,2-Epoxypropane: a chirality center1,2-Epoxypropane: a chirality centercan be part of a ringcan be part of a ring

OO

HH22CC CHCHCHCH33

attached to the chirality center are:attached to the chirality center are:

——HH

——CHCH33

——OCHOCH22

——CHCH22OO

Dr. Wolf's CHM 201 & 202 7-20


Limonene: a chirality Limonene: a chirality center can be part of a center can be part of a ringring

CHCH33

HH CC

CHCH33

CHCH22

attached to theattached to thechirality center are:chirality center are:

——HH

——CHCH22CHCH22

——CHCH22CH=CCH=C

——C=CC=C

Dr. Wolf's CHM 201 & 202 7-21


Chiral as a result of isotopic substitutionChiral as a result of isotopic substitution

CHCH33CCDD

TT

HH

Dr. Wolf's CHM 201 & 202 7-22

A molecule with a single chirality centerA molecule with a single chirality centermust be chiral.must be chiral.

But, a molecule with two or more But, a molecule with two or more chirality centers may be chiralchirality centers may be chiral

or it may not (Sections 7.10-7.13). or it may not (Sections 7.10-7.13).

Dr. Wolf's CHM 201 & 202 7-23

Symmetry in Achiral Symmetry in Achiral StructuresStructures

Dr. Wolf's CHM 201 & 202 7-24

Symmetry tests for Symmetry tests for achiralachiral structures structuresSymmetry tests for Symmetry tests for achiralachiral structures structures

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..

Dr. Wolf's CHM 201 & 202 7-25

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

Dr. Wolf's CHM 201 & 202 7-26

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

Dr. Wolf's CHM 201 & 202 7-27

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

Dr. Wolf's CHM 201 & 202 7-28

Properties of Chiral Molecules:Properties of Chiral Molecules:

Optical ActivityOptical Activity

Dr. Wolf's CHM 201 & 202 7-29

A substance is optically active if it rotates A substance is optically active if it rotates the plane of polarized light.the plane of polarized light.

In order for a substance to exhibit opticalIn order for a substance to exhibit opticalactivity, it must be chiral and one enantiomer activity, it must be chiral and one enantiomer must be present in excess of the other.must be present in excess of the other.

Optical ActivityOptical ActivityOptical ActivityOptical Activity

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

LightLightLightLight

has wave propertieshas wave properties

periodic increase and decrease in amplitude of periodic increase and decrease in amplitude of wavewave

Dr. Wolf's CHM 201 & 202 7-31

LightLightLightLight

optical activity is usually measured using light optical activity is usually measured using light having a wavelength of 589 nmhaving a wavelength of 589 nmthis is the wavelength of the yellow light from a this is the wavelength of the yellow light from a sodium lamp and is called the D line of sodiumsodium lamp and is called the D line of sodium

Dr. Wolf's CHM 201 & 202 7-32

Polarized lightPolarized light

ordinary ordinary (nonpolarized) (nonpolarized) light consists of light consists of many beams many beams vibrating in vibrating in different planesdifferent planes

plane-polarized plane-polarized light consists of light consists of only those beams only those beams that vibrate in the that vibrate in the same planesame plane

Dr. Wolf's CHM 201 & 202 7-33

Nicol prismNicol prism

Polarization of lightPolarization of light

Dr. Wolf's CHM 201 & 202 7-34

Rotation of plane-polarized lightRotation of plane-polarized light

Dr. Wolf's CHM 201 & 202 7-35

observed rotation (observed rotation () depends on the number ) depends on the number of molecules encountered and is proportional to:of molecules encountered and is proportional to:

path length (path length (ll), ), andand concentration ( concentration (cc))

therefore, define specific rotation [therefore, define specific rotation [] as:] as:

Specific rotationSpecific rotation

100 100

clcl

concentration = g/100 mLconcentration = g/100 mLlength in decimeterslength in decimeters

[[] =] =

Dr. Wolf's CHM 201 & 202 7-36

a mixture containing equal quantities a mixture containing equal quantities of enantiomers is called a of enantiomers is called a racemic mixtureracemic mixture

a racemic mixture is a racemic mixture is optically inactiveoptically inactive(( = 0) = 0)

a sample that is optically inactive can bea sample that is optically inactive can beeither an achiral substance or a racemiceither an achiral substance or a racemicmixturemixture

Racemic mixtureRacemic mixture

Dr. Wolf's CHM 201 & 202 7-37

an an optically pure optically pure substance consists exclusively substance consists exclusively of a single enantiomerof a single enantiomer

enantiomeric excess enantiomeric excess = = % one enantiomer – % other enantiomer% one enantiomer – % other enantiomer

% optical purity % optical purity = = enantiomeric excess enantiomeric excess

e.g. 75% (-) – 25% (+) = 50% opt. pure (-)e.g. 75% (-) – 25% (+) = 50% opt. pure (-)

Optical purityOptical purityOptical purityOptical purity

Dr. Wolf's CHM 201 & 202 7-38

Absoluteand

Relative Configuration

Dr. Wolf's CHM 201 & 202 7-39

Relative configurationRelative configuration compares the compares the arrangement of atoms in space of one compound arrangement of atoms in space of one compound with those of another.with those of another.

until the 1950s, all configurations were relativeuntil the 1950s, all configurations were relative

Absolute configurationAbsolute configuration is the precise is the precise arrangement of atoms in space.arrangement of atoms in space.

we can now determine the absolute we can now determine the absolute configuration of almost any compoundconfiguration of almost any compound

ConfigurationConfigurationConfigurationConfiguration

Dr. Wolf's CHM 201 & 202 7-40

No bonds are made or broken at the stereogenic centerNo bonds are made or broken at the stereogenic center

in this experiment. Therefore, when (+)-3-buten-2-ol in this experiment. Therefore, when (+)-3-buten-2-ol

and (+)-2-butanol have the same sign of rotation, the and (+)-2-butanol have the same sign of rotation, the

arrangement of atoms in space is analogous. The twoarrangement of atoms in space is analogous. The two

have the same relative configuration.have the same relative configuration.

CHCH33CHCHCHCH22CHCH33

OHOH

HH22,, PdPd

[[] + 33.2°] + 33.2° [[] + 13.5°] + 13.5°

Relative configurationRelative configurationRelative configurationRelative configuration

CHCH33CHCHCHCH

OHOH

CHCH22

Dr. Wolf's CHM 201 & 202 7-41

HHHOHO

HH OHOH HH22, Pd, Pd

HHHOHOHH22, Pd, Pd

HH OHOH

Two possibilitiesTwo possibilitiesTwo possibilitiesTwo possibilities

But in the absence of additional information, we can't tell But in the absence of additional information, we can't tell which structure corresponds towhich structure corresponds to(+)-3-buten-2-ol, and which one to (–)-3-buten-2-ol.(+)-3-buten-2-ol, and which one to (–)-3-buten-2-ol.

Dr. Wolf's CHM 201 & 202 7-42

HHHOHO


HHHOHOHH22, Pd, Pd

HH OHOH

Two possibilitiesTwo possibilitiesTwo possibilitiesTwo possibilities

Nor can we tell which structure corresponds toNor can we tell which structure corresponds to(+)-2-butanol, and which one to (–)-2-butanol.(+)-2-butanol, and which one to (–)-2-butanol.

Dr. Wolf's CHM 201 & 202 7-43

HHHOHO


HHHOHOHH22, Pd, Pd

HH OHOH

Absolute configurationsAbsolute configurationsAbsolute configurationsAbsolute configurations

[[] +13.5°] +13.5°[[] +33.2°] +33.2°

[[] –33.2°] –33.2° [[] –13.5°] –13.5°

Dr. Wolf's CHM 201 & 202 7-44

Not all compounds that have the same relativeNot all compounds that have the same relative

configuration have the same sign of rotation. No bondsconfiguration have the same sign of rotation. No bonds

are made or broken at the stereogenic center in theare made or broken at the stereogenic center in the

reaction shown, so the relative positions of the atoms reaction shown, so the relative positions of the atoms

are the same. Yet the sign of rotation changes.are the same. Yet the sign of rotation changes.

CHCH33CHCH22CHCHCHCH22BrBr

CHCH33

HBrHBr

[[] -5.8°] -5.8° [[] + 4.0°] + 4.0°

Relative configurationRelative configurationRelative configurationRelative configuration

CHCH33CHCH22CHCHCHCH22OHOH

CHCH33

Dr. Wolf's CHM 201 & 202 7-45

The Cahn-Ingold-Prelog The Cahn-Ingold-Prelog

R-SR-S

Notational SystemNotational System

Dr. Wolf's CHM 201 & 202 7-46

1. 1. need rules for need rules for rankingranking substituents at substituents at stereogenic center in order of decreasing stereogenic center in order of decreasing precedenceprecedence

2. 2. need convention for need convention for orientingorienting molecule so molecule so that order of appearance of substituents that order of appearance of substituents can be compared with rank can be compared with rank

The system that is used was devised by The system that is used was devised by R. S. Cahn, Sir Christopher Ingold, and R. S. Cahn, Sir Christopher Ingold, and V. Prelog.V. Prelog.

Two requirements for a systemTwo requirements for a systemfor specifying absolute configurationfor specifying absolute configuration

Two requirements for a systemTwo requirements for a systemfor specifying absolute configurationfor specifying absolute configuration

Dr. Wolf's CHM 201 & 202 7-47

1. Rank the substituents at the stereogenic 1. Rank the substituents at the stereogenic center according to same rules used in center according to same rules used in EE--ZZ notation. notation.

2. Orient the molecule so that lowest-ranked 2. Orient the molecule so that lowest-ranked substituent points away from you. substituent points away from you.

The Cahn-Ingold-Prelog RulesThe Cahn-Ingold-Prelog Rules(Table 7.1)(Table 7.1)


Dr. Wolf's CHM 201 & 202 7-48

43

2

1

ExampleExampleExampleExample

4 3

2

1

Order of decreasing rank:Order of decreasing rank:44 > > 33 > 2 > > 2 > 11

Dr. Wolf's CHM 201 & 202 7-49

• 1. Rank the substituents at the stereogenic 1. Rank the substituents at the stereogenic center according to same rules used in center according to same rules used in EE--ZZ notation. notation.

• 2. Orient the molecule so that lowest-ranked 2. Orient the molecule so that lowest-ranked substituent points away from you.substituent points away from you.

• 3. If the order of decreasing precedence traces 3. If the order of decreasing precedence traces a clockwise path, the absolute configuration a clockwise path, the absolute configuration is is RR. If the path is anticlockwise, the . If the path is anticlockwise, the configuration is configuration is SS..



Dr. Wolf's CHM 201 & 202 7-50

43

2

1


4 3

2

1

Order of decreasing rank:Order of decreasing rank:44 33 2 2

clockwiseclockwiseRR

anticlockwiseanticlockwiseSS

Dr. Wolf's CHM 201 & 202 7-51

((SS)-2-Butanol)-2-Butanol

CC OHOH

HH33CC

HHCHCH33CHCH22

Enantiomers of 2-butanolEnantiomers of 2-butanolEnantiomers of 2-butanolEnantiomers of 2-butanol CCHOHO

CHCH33

HHCHCH22CHCH33

((RR)-2-Butanol)-2-Butanol

Dr. Wolf's CHM 201 & 202 7-52

Very important!Very important!Very important!Very important!

Two different compounds with the Two different compounds with the same sign of rotation need not have same sign of rotation need not have the same configuration.the same configuration.

Dr. Wolf's CHM 201 & 202 7-53

HHHH33CC

HH

HH

Chirality center in a ringChirality center in a ringChirality center in a ringChirality center in a ring

RR

——CHCH22C=C > —CHC=C > —CH22CHCH2 2 > > —CH—CH33 > —H > —H

Dr. Wolf's CHM 201 & 202 7-54

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.

Dr. Wolf's CHM 201 & 202 7-55

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

Dr. Wolf's CHM 201 & 202 7-56


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

Dr. Wolf's CHM 201 & 202 7-57


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

Dr. Wolf's CHM 201 & 202 7-58

Physical Properties of Physical Properties of EnantiomersEnantiomers

Dr. Wolf's CHM 201 & 202 7-59

Same:Same: melting point, boiling point, density, etcmelting point, boiling point, density, 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

Dr. Wolf's CHM 201 & 202 7-60

OO OO

CHCH33 CHCH33

HH33CC HH33CCCHCH22 CHCH22

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

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

Dr. Wolf's CHM 201 & 202 7-61

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

Dr. Wolf's CHM 201 & 202 7-62

Reactions That Create A Reactions That Create A

Chiral CenterChiral Center

Dr. Wolf's CHM 201 & 202 7-63

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.

Dr. Wolf's CHM 201 & 202 7-64


CHCH33CHCH CHCH22

CHCH33COOHCOOH

OO

HH33CC

OO

CHCH22CC

HH

Chiral, but racemicChiral, but racemicAchiralAchiral

Dr. Wolf's CHM 201 & 202 7-65

epoxidation from this direction epoxidation from this direction

gives gives RR epoxide epoxide

RR

Dr. Wolf's CHM 201 & 202 7-66




gives gives SS epoxide epoxide

RR

SS

Dr. Wolf's CHM 201 & 202 7-67

50%50%

50%50%




gives gives SS epoxide epoxide

RR

SS

Dr. Wolf's CHM 201 & 202 7-68


CHCH33CHCH CHCH22

Chiral, but racemicChiral, but racemic

BrBr22, H, H22OO

CHCH33CHCHCHCH22BrBr

OHOH

AchiralAchiral

Dr. Wolf's CHM 201 & 202 7-69


CHCH33CHCH CHCHCHCH33


HBrHBrCHCH33CHCHCHCH22CHCH33

BrBr

AchiralAchiral

Dr. Wolf's CHM 201 & 202 7-70

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

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

However, if the reactant is racemic, the product will be However, if the reactant is racemic, the product will be racemic also.racemic also.

Remember: Remember: "Optically inactive starting materials can't "Optically inactive starting materials can't give optically active products."give optically active products."

Dr. Wolf's CHM 201 & 202 7-71



HBrHBrCHCH33CHCHCHCH22CHCH33

OHOH

CHCH33CHCHCHCH22CHCH33

BrBr


Dr. Wolf's CHM 201 & 202 7-72

Many biochemical reactions convertMany biochemical reactions convertan achiral reactant to a singlean achiral reactant to a singleenantiomer of a chiral productenantiomer of a chiral product

Many biochemical reactions convertMany biochemical reactions convertan achiral reactant to a singlean achiral reactant to a singleenantiomer of a chiral productenantiomer of a chiral product

Reactions in living systems are catalyzed by enzymes, Reactions in living systems are catalyzed by enzymes, which are enantiomerically homogeneous.which are enantiomerically homogeneous.

The enzyme (catalyst) is part of the reacting system, so The enzyme (catalyst) is part of the reacting system, so such reactions don't violate the generalization that such reactions don't violate the generalization that "Optically inactive starting materials can't give "Optically inactive starting materials can't give optically active products."optically active products."

Dr. Wolf's CHM 201 & 202 7-73


fumarasefumarase

HH22OO

CC CC

HOHO22CC HH

COCO22HHHH

CC OHOH

HHHOHO22CC

HOHO22CCHCCH22

Fumaric acidFumaric acid ((SS)-(–)-Malic acid)-(–)-Malic acid

AchiralAchiral Single enantiomerSingle enantiomer

Dr. Wolf's CHM 201 & 202 7-74

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?

Dr. Wolf's CHM 201 & 202 7-75

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

Dr. Wolf's CHM 201 & 202 7-76


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

Dr. Wolf's CHM 201 & 202 7-77


4 Combinations = 4 Stereoisomers4 Combinations = 4 Stereoisomers

OO


HOHO OHOH

2233


Dr. Wolf's CHM 201 & 202 7-78


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


Dr. Wolf's CHM 201 & 202 7-79


OO


HOHO OHOH

2233


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

Dr. Wolf's CHM 201 & 202 7-80

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°

Dr. Wolf's CHM 201 & 202 7-81


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

Dr. Wolf's CHM 201 & 202 7-82



diastereomersdiastereomersenantiomersenantiomers

Dr. Wolf's CHM 201 & 202 7-83

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°

Dr. Wolf's CHM 201 & 202 7-84

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

Dr. Wolf's CHM 201 & 202 7-85

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

Dr. Wolf's CHM 201 & 202 7-86

Fischer projections Fischer projections Fischer projections Fischer projections

COCO22HH

CHCH33

OHOH

OHOH

HH

HH

Dr. Wolf's CHM 201 & 202 7-87

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

Dr. Wolf's CHM 201 & 202 7-88

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

Dr. Wolf's CHM 201 & 202 7-89

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

Dr. Wolf's CHM 201 & 202 7-90

SS SSRR RR

Two chirality centers in a ringTwo chirality centers in a ringTwo chirality centers in a ringTwo chirality centers in a ring

nonsuperposable mirror images; enantiomersnonsuperposable mirror images; enantiomers

transtrans-1-Bromo-2-chlorocyclopropane-1-Bromo-2-chlorocyclopropane

Dr. Wolf's CHM 201 & 202 7-91

SS RRSS RR


nonsuperposable mirror images; enantiomersnonsuperposable mirror images; enantiomers

ciscis-1-Bromo-2-chlorocyclopropane-1-Bromo-2-chlorocyclopropane

Dr. Wolf's CHM 201 & 202 7-92

SS RRSS RR


stereoisomers that are not enantiomers; diastereomersstereoisomers that are not enantiomers; diastereomers

ciscis-1-Bromo-2-chloro--1-Bromo-2-chloro-cyclopropanecyclopropane

transtrans-1-Bromo-2-chloro--1-Bromo-2-chloro-cyclopropanecyclopropane

Dr. Wolf's CHM 201 & 202 7-93

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.

Dr. Wolf's CHM 201 & 202 7-94

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

Dr. Wolf's CHM 201 & 202 7-95

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

Dr. Wolf's CHM 201 & 202 7-96


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

Dr. Wolf's CHM 201 & 202 7-97


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

chiralchiral chiralchiral

these two arethese two areenantiomersenantiomers

Dr. Wolf's CHM 201 & 202 7-98


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

chiralchiral chiralchiral

CHCH33

CHCH33

OHOHHH

HHHOHOHH OHOH

CHCH33

CHCH33

HHHOHOthese two arethese two areenantiomersenantiomers

Dr. Wolf's CHM 201 & 202 7-99


22RR,3,3SS

achiralachiral

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

Dr. Wolf's CHM 201 & 202 7-100


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

Dr. Wolf's CHM 201 & 202 7-101


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

Dr. Wolf's CHM 201 & 202 7-102


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

Dr. Wolf's CHM 201 & 202 7-103


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.

Dr. Wolf's CHM 201 & 202 7-104

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 and cyclopropane; the achiral (meso) cis isomer and two enantiomers of the trans isomer.two enantiomers of the trans isomer.

Cyclic compoundsCyclic compoundsCyclic compoundsCyclic compounds

Dr. Wolf's CHM 201 & 202 7-105

MoleculesMolecules

withwith

Multiple Chirality CentersMultiple Chirality Centers

Dr. Wolf's CHM 201 & 202 7-106

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?

Dr. Wolf's CHM 201 & 202 7-107


4 chirality centers4 chirality centers

16 stereoisomers16 stereoisomers

OO

HOCHHOCH22CCH—H—CCH—H—CCH—H—CCHCHHCH

OHOH OHOH OHOH OHOH

Dr. Wolf's CHM 201 & 202 7-108

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

Dr. Wolf's CHM 201 & 202 7-109

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?

Dr. Wolf's CHM 201 & 202 7-110

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

Dr. Wolf's CHM 201 & 202 7-111

Chemical Reactions That Chemical Reactions That

Produce Diastereomers Produce Diastereomers

Dr. Wolf's CHM 201 & 202 7-112

In order to know understand stereochemistry of In order to know understand stereochemistry of product, you need to know two things:product, you need to know two things:

(1) stereochemistry of alkene (cis or trans; Z or E)(1) stereochemistry of alkene (cis or trans; Z or E) (2) stereochemistry of mechanism (syn or anti)(2) stereochemistry of mechanism (syn or anti)

Stereochemistry of Addition to AlkenesStereochemistry of Addition to AlkenesStereochemistry of Addition to AlkenesStereochemistry of Addition to Alkenes

CC CC ++ E—YE—Y CC CCEE YY

Dr. Wolf's CHM 201 & 202 7-113

BrBr22

RR

SS RR

SS

mesomeso

anti addition to anti addition to transtrans-2-butene gives meso -2-butene gives meso diastereomerdiastereomer

Bromine Addition to trans-2-ButeneBromine Addition to trans-2-ButeneBromine Addition to trans-2-ButeneBromine Addition to trans-2-Butene

Dr. Wolf's CHM 201 & 202 7-114

BrBr22

RR

RR SS

SS

50%50% 50%50%

Bromine Addition to cis-2-ButeneBromine Addition to cis-2-ButeneBromine Addition to cis-2-ButeneBromine Addition to cis-2-Butene

anti addition to anti addition to ciscis-2-butene gives racemic mixture -2-butene gives racemic mixture of chiral diastereomerof chiral diastereomer

++

Dr. Wolf's CHM 201 & 202 7-115

RCORCO33HH

RR

RR SS

SS

syn addition to syn addition to transtrans-2-butene gives racemic -2-butene gives racemic mixture of chiral diastereomermixture of chiral diastereomer

Epoxidation of trans-2-ButeneEpoxidation of trans-2-ButeneEpoxidation of trans-2-ButeneEpoxidation of trans-2-Butene

50%50% 50%50%

++

Dr. Wolf's CHM 201 & 202 7-116

RR

SS RR

SS

Epoxidation of cis-2-ButeneEpoxidation of cis-2-ButeneEpoxidation of cis-2-ButeneEpoxidation of cis-2-Butene

syn addition to syn addition to ciscis-2-butene gives meso -2-butene gives meso diastereomerdiastereomer

RCORCO33HH

mesomeso

Dr. Wolf's CHM 201 & 202 7-117

Of two stereoisomers of a particular starting Of two stereoisomers of a particular starting material, each one gives differentmaterial, each one gives differentstereoisomeric forms of the productstereoisomeric forms of the product

Related to mechanism: terms such asRelated to mechanism: terms such assyn addition and anti addition refer tosyn addition and anti addition refer tostereospecificitystereospecificity

Stereospecific reactionStereospecific reactionStereospecific reactionStereospecific reaction

Dr. Wolf's CHM 201 & 202 7-118

..

transtrans-2-butene-2-butene

ciscis-2-butene-2-butene

transtrans-2-butene-2-butene

ciscis-2-butene-2-butene brominationbromination antianti 22RR,3,3RR + 2 + 2SS,3,3SS

brominationbromination

epoxidationepoxidation

epoxidationepoxidation

antianti

synsyn

synsyn

mesomeso

mesomeso

22RR,3,3RR + 2 + 2SS,3,3SS

Stereospecific reactionsStereospecific reactionsStereospecific reactionsStereospecific reactions

Dr. Wolf's CHM 201 & 202 7-119

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

Dr. Wolf's CHM 201 & 202 7-120

Resolution of EnantiomersResolution of Enantiomers

Separation of a racemic mixture into its two Separation of a racemic mixture into its two enantiomeric formsenantiomeric forms

Dr. Wolf's CHM 201 & 202 7-121

enantiomersenantiomers

C(+)C(+)C(+)C(+) C(-)C(-)C(-)C(-)

StrategyStrategyStrategyStrategy

Dr. Wolf's CHM 201 & 202 7-122


C(+)C(+)C(+)C(+) C(-)C(-)C(-)C(-)

2P(+)2P(+)

C(+)C(+)P(+)C(+)C(+)P(+) C(-)C(-)P(+)C(-)C(-)P(+)

diastereomersdiastereomers


Dr. Wolf's CHM 201 & 202 7-123


C(+)C(+)C(+)C(+) C(-)C(-)C(-)C(-)

2P(+)2P(+)

C(+)C(+)P(+)C(+)C(+)P(+) C(-)C(-)P(+)C(-)C(-)P(+)


C(+)C(+)P(+)C(+)C(+)P(+)

C(-)C(-)P(+)C(-)C(-)P(+)


Dr. Wolf's CHM 201 & 202 7-124


C(+)C(+)C(+)C(+) C(-)C(-)C(-)C(-)

2P(+)2P(+)

C(+)C(+)P(+)C(+)C(+)P(+) C(-)C(-)P(+)C(-)C(-)P(+)


C(+)C(+)P(+)C(+)C(+)P(+)

C(-)C(-)P(+)C(-)C(-)P(+)

P(+)P(+)

P(+)P(+)

C(+)C(+)C(+)C(+)

C(-)C(-)C(-)C(-)


Dr. Wolf's CHM 201 & 202 7-125

Stereoregular PolymersStereoregular Polymers

atacticatactic

isotacticisotactic

syndiotacticsyndiotactic

Dr. Wolf's CHM 201 & 202 7-126

Atactic PolypropyleneAtactic PolypropyleneAtactic PolypropyleneAtactic Polypropylene

random stereochemistry of methyl groups random stereochemistry of methyl groups attached to main chain (stereorandom)attached to main chain (stereorandom)

properties not very useful for fibers etc.properties not very useful for fibers etc.

formed by free-radical polymerizationformed by free-radical polymerization

Dr. Wolf's CHM 201 & 202 7-127

Isotactic PolypropyleneIsotactic PolypropyleneIsotactic PolypropyleneIsotactic Polypropylene

stereoregular polymer; all methyl groups onstereoregular polymer; all methyl groups onsame side of main chainsame side of main chainuseful propertiesuseful propertiesprepared by coordination polymerization prepared by coordination polymerization under Ziegler-Natta conditionsunder Ziegler-Natta conditions

Dr. Wolf's CHM 201 & 202 7-128

Syndiotactic PolypropyleneSyndiotactic PolypropyleneSyndiotactic PolypropyleneSyndiotactic Polypropylene

stereoregular polymer; methyl groups alternate stereoregular polymer; methyl groups alternate side-to-side on main chainside-to-side on main chain

useful propertiesuseful properties

prepared by coordination polymerization under prepared by coordination polymerization under Ziegler-Natta conditionsZiegler-Natta conditions

Dr. Wolf's CHM 201 & 202 7-129

Chirality CentersChirality CentersOther Than CarbonOther Than Carbon

Dr. Wolf's CHM 201 & 202 7-130

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

Dr. Wolf's CHM 201 & 202 7-131

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

Dr. Wolf's CHM 201 & 202 7-132

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

Dr. Wolf's CHM 201 & 202 7-133

Sulfur in sulfoxidesSulfur in sulfoxidesSulfur in sulfoxidesSulfur in sulfoxides

Pyramidal geometry at sulfur can produce a chiral Pyramidal geometry at sulfur can produce a chiral structure; pyramidal inversion is slow and structure; pyramidal inversion is slow and compounds of the type shown have been resolvedcompounds of the type shown have been resolved

SS SS:: ::

aabb

O_O_

aabb

O_O_

slowslow

++ ++

Dr. Wolf's CHM 201 & 202 7-134

End of Chapter 7

dr. wolf's chm 201 & 202 7-1 chapter 7 stereochemistry

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