hougland che275 chapter7 slides

Organic Chemistry

CHE 275

Chapter 7Stereochemistry

• A molecule is chiral if its two mirror image

forms are not superimposable upon one another.

• A molecule is achiral if its two mirror image

forms are superimposable.

Chirality

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

Bromochlorofluoromethaneis Chiral

Br

ClH

FTo show nonsuperimposability, rotate this model 180°around a vertical axis.


Br

ClH

F

Br

ClH

F


Br

ClH

F

Br

Cl

H F

AnotherLook

are enantiomers with respect to each other

and

nonsuperimposable mirror images are called enantiomers

EnantiomersIsomers

stereoisomersconstitutionalisomers

diastereomersenantiomers

Chlorodifluoromethaneis Achiral

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

Chlorodifluoromethaneis Achiral

a carbon atom with fourdifferent groups attached to it

also called:chiral centerasymmetric centerstereocenterstereogenic center

w

x y

z

C

The Chirality Center

A molecule with a single chirality center is chiral.

Bromochlorofluoromethane is an example.

Cl F

Br

H

C

Chirality and Chirality Centers

A molecule with a single chirality center is chiral.

2-Butanol is another example.

CH3

OH

H

C CH2CH3

Chirality and Chirality Centers

CH3

C

CH2CH3

CH2CH2CH2CH3CH3CH2CH2

a chiral alkane

One Chirality Center

Interactive Question

Which one of the following is achiral?

A) 2-chloropentane

B) 3-chloropentane

C) 1,2-dichloropentane

D) 1,3-dichloropentane

Linalool, a naturally occurring chiral alcohol

OH


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

O

H2C CHCH3

attached to the chirality center are:

—H

—CH3

—OCH2

—CH2O


Limonene: a chirality center can be part of a ring

CH3

H C

CH3

CH2

attached to thechirality center are:

—H

—CH2CH2

—CH2CH=

—C=


Chiral as a result of isotopic substitution

CH3CD

T

H

One Chirality CenterA molecule with a single

chirality center must be chiral.

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

or it may not (Sections 7.10-7.14).

Symmetry tests for achiral structures

Any molecule with a plane of symmetryor a center of symmetry must be achiral.

A plane of symmetry bisects a molecule into two

mirror image halves. Chlorodifluoromethane

has a plane of symmetry.

A Plane of Symmetry

Plane of Symmetry

• The plane has the same thing on both sides for the flask

• There is no mirror plane for a hand

• We can apply this same analysis to molecules

A plane of symmetry bisects a molecule into two

mirror image halves.

1-Bromo-1-chloro-2-fluoroethene has a plane

of symmetry.

A Plane of Symmetry

A point in the center of themolecule is a center of symmetry if a line drawn from it to any element, when extended an equal distance in the opposite direction, encounters an identical element.

A Center of Symmetry Interactive Question

Which one of the following compounds is chiral?

A) 1-methylcyclohexanol

B) cis-2-methylcyclohexanol

C) trans-4-methylcyclohexanol

D) cyclohexanol

A substance is optically active if it rotates

the plane of polarized light.

In order for a substance to exhibit optical

activity, it must be chiral and one enantiomer

must be present in excess of the other.

Optical Activity

• has wave properties

• periodic increase and decrease in amplitude of wave

Light

• optical activity is usually measured using light having a wavelength of 589 nm

• this is the wavelength of the yellow light from a sodium lamp and is called the D line of sodium

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

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

Polarized Light

Polarization of Light

Nicol prism

Rotation of Plane-Polarized Light

observed rotation () depends on the number

of molecules encountered and is proportional to:

path length (l), and concentration (c)

therefore, define specific rotation [] as:

100

cl

concentration = g/100 mLlength in decimeters

[] =

Specific Rotation

a mixture containing equal quantities

of enantiomers is called a racemic mixture

a racemic mixture is optically inactive

( = 0)

a sample that is optically inactive can be

either an achiral substance or a racemic

mixture

Racemic Mixtures

an optically pure substance consists exclusively

of a single enantiomer

enantiomeric excess =

% one enantiomer – % other enantiomer

% optical purity = enantiomeric excess

Optical Purity

Which of the molecules below is optically active?

A) 1 only

B) 1 and 3

C) 1 and 2

D) 1, 2 and 3


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

Absolute configuration is the precise arrangement of atoms in space.

Configuration

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

until the 1950s, all configurations were relative

Absolute configuration is the precise arrangement of atoms in space.

we can now determine the absolute configuration of almost any compound

Configuration

No bonds are made or broken at the chirality center

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

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

arrangement of atoms in space is analogous. The two

have the same relative configuration.

CH3CHCH2CH3

OH

Pd

[] + 33.2° [] + 13.5°

CH3CHCH

OH

CH2

Relative Configuration

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

Two Possibilities

OHH

HHO

Pd, H2 OHH

Pd, H2 HHO

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

Two Possibilities

OHH

HHO

Pd, H2 OHH

Pd, H2 HHO

Absolute Configurations

OHH

HHO

Pd, H2 OHH

Pd, H2 HHO

[] = +13.5°

[] = -13.5° [] = -33.2°

[] = +33.2°

Not all compounds that have the same relative

configuration have the same sign of rotation. No bonds

are made or broken at the chirality center in the

reaction shown, so the relative positions of the atoms

are the same. Yet the sign of rotation changes.

CH3CH2CHCH2Br

CH3

HBr

[] -5.8° [] + 4.0°

CH3CH2CHCH2OH

CH3

Relative Configuration

1. need rules for ranking substituents at chirality center in order of decreasing precedence

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

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

Two requirements for a systemfor specifying absolute configuration

1. Rank the substituents at the chirality

center according to same rules used in

E-Z notation.

2. Orient the molecule so that lowest-ranked

substituent points away from you.

Cahn-Ingold-Prelog Rules(Table 7.1)

Order of decreasing rank:4 > 3 > 2 > 1

Example

1. Rank the substituents at the chirality center according to same rules used in E-Z notation.

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

3. If the order of decreasing precedence traces a clockwise path, the absolute configuration is R. If the path is counterclockwise, the configuration is S.

The CIP Rules

Order of decreasing rank:4 3 2

clockwiseR

counterclockwiseS

Example


Which one of the following groups has the highest ranking when precedence is assigned according to the Cahn-Ingold-Prelog rules?

A) -CH=CH2

B) -CH=O

C) -CH2CH2Br

D) -CH2F

R-Configuration at ChiralCenter

• Lowest priority group is pointed away and

direction of higher 3 is clockwise, or right turn

S-Configuration at ChiralCenter

• Lowest priority group is pointed away and

direction of higher 3 is counterclockwise, or left turn

C OH

H3C

HCH3CH2

CHO

CH3

HCH2CH3

(S)-2-Butanol (R)-2-Butanol

Enantiomers of 2-Butanol


Determine the absolute configuration of the molecule shown.

A) (S)

B) (R)

C) not optically active

Very important! Two different compounds with the same sign of rotation need not

have the same configuration.

Verify this statement by doing Problem 7.9 on page 289. All four compounds have positive rotations. What are their configurations according to the Cahn-Ingold-Prelog rules?

HH3C

H

H

R

—CH2C=C > —CH2CH2 > —CH3 > —H

Chirality Center in a RingInteractive Question

What is the absolute configuration of the molecule shown?

A) (R)

B) (S)

C) not optically active

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

Fischer Projections

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

Rules for Fischer Projections

Br Cl

F

H

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

Br Cl

F

H


Br Cl

F

H


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

Same:melting point, boiling point, density, etc

Different: properties that depend on shape of molecule (biological-physiological properties) can bedifferent

Physical Properties of Enantiomers

Why is Chirality Important?

• Chirality is important because of the structure of all of the proteins in your body• Consider the above structure of myoglobin, a muscle protein found in sea mammals

Proteins Are Made Up of Amino Acids

Amino Acids Are Chiral

• All proteins are made up of the same 20 amino acids

• 19 of the 20 amino acids are chiral

• This means that all biological interactions are by definition

chiral

• Enantiomers of the same molecule may have completely

different biological properties

H2N CO2H

CH3H

Alanine

H2N CO2H

H

Phenylalanine

H2N CO2H

H

Serine

HO

H2N CO2H

H

Tryptophan

HN

Chirality in Nature

• Stereoisomers are readily distinguished by chiral proteins(receptors) in nature

• Properties of drugs depend on stereochemistry

• Think of biological recognition as equivalent to 3-point

interaction

Many Drugs Are Chiral

• When drugs are made and sold only one enantiomer ismarketed

• This is because the other enantiomer sometimes hastoxic properties

• An exception is Ibuprofen, which is sold as a racemate• Only one enantiomer is active, but it racemizes in the body anyway

N

S CH3

CH3

CO2H

HHN

O

H

OO

Penicillin V

CH3

CO2HH

(S) - Ibuprofin(S)- Ibuprofen

O O

CH3 CH3

H3C H3CCH2 CH2

(–)-Carvonespearmint oil

(+)-Carvonecaraway seed oil

Odor The Chirality Axis

A diverse group of molecules are chiral but do not contain a chirality center. Some of these contain a chirality axis-an axis about which groups are arranged so that the spatial arrangement is not superimposable on its mirror image.

Examples include substituted biphenyls and allenes:

A

BY

X

In the appropriately substituted biphenyls, rotation around the bond joining the rings is slowed and the enantiomers can be isolated:

A

BY

X

Conformational isomers that are stable, isolable compounds are called atropisomers.

P(C6H5)2

P(C6H5)2

Substituted 1,1’-binaphthyl derivatives exhibit atropisomerism due to hindered rotation about the single bond that connects the two naphthalene rings.

Example: (S)-(-)-BINAP

(discussed further next semester)

If all of the components of the starting state (reactants, catalysts, solvents, etc.) are achiral, any chiral product will be formed as a racemic mixture.

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

Remember: In order for a substance to be optically active, it must be chiral and one enantiomer must be present in greater amounts than the other.

Chiral Reaction Products

CH3CH CH2

CH3COOH

O

H3C

O

CH2C

H

Chiral, but racemicAchiral

Example

50%

50%

Epoxidation from this direction gives S epoxide

Epoxidation from this direction gives R epoxide

R

S

CH3CH CH2

Chiral, but racemic

Br2, H2O

CH3CHCH2Br

OH

Achiral

Example

CH3CH2CH CH3

HBrCH3CHCH2CH3

Br

Example

Chiral, but racemicAchiral

Mirror Image Transition States• Transition states are mirror images and product is racemic

Many Reactions Convert Chiral Reactants to Chiral Products

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

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

Chiral, but racemic

HBrCH3CHCH2CH3

OH

CH3CHCH2CH3

Br

Chiral, but racemic

Example

Reactions in living systems are catalyzed by enzymes, which are enantiomericallyhomogeneous.

The enzyme (catalyst) is part of the reacting system

Such reactions don't violate the generalization that

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

Biochemical Reactions

fumarase

H2O

C C

HO2C H

CO2HH

C OH

HHO2C

HO2CCH2

Fumaric acid (S)-(–)-Malic acid

Achiral Single enantiomer

Example

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

Molecules with Two Chirality Centers

What are all the possible R and S combinations of the two chirality centers in this molecule?

O

CH3CHCHCOH

HO OH

23

Carbon-2 R R S SCarbon-3 R S R S

2,3-Hydroxybutanoic Acid

4 Combinations = 4 Stereoisomers

O

CH3CHCHCOH

HO OH

23



4 Combinations = 4 Stereoisomers

What is the relationship between these stereoisomers?

O

CH3CHCHCOH

HO OH

23



O

CH3CHCHCOH

HO OH

23


enantiomers: 2R,3R and 2S,3S2R,3S and 2S,3R

2,3-Hydroxybutanoic AcidHO

CO2H

CH3

H

OHHR

R

CO2H

CH3

H

HHO

OH

S

S

CO2H

H

CH3

HO

HHO

R

S

CO2H

CH3

H OH

OHHR

S

enantiomers

enantiomers

[] = -9.5° [] = +9.5°

[] = -17.8°[] = +17.8°

O

CH3CHCHCOH

HO OH

23


But not all relationships are enantiomeric

Stereoisomers that are not enantiomers are diastereomers

2,3-Dihydroxybutanoic Acid Isomers

stereoisomersconstitutionalisomers

diastereomersenantiomers

HO

CO2H

CH3

H

OHHR

R

CO2H

CH3

H

HHO

OH

S

S

CO2H

H

CH3

HO

HHO

R

S

CO2H

CH3

H OH

OHHR

S

[] = -9.5° [] = +9.5°

[] = -17.8°[] = +17.8°

enantiomers

enantiomers

diastereomers

CO2H

CH3

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

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

Fischer Projections

transform molecule to eclipsed conformation in order to construct Fischer projection

Fischer Projections

CO2H

CH3

OH

OH

H

H

Fischer Projections

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

easiest to apply using Fischer projections

orientation: vertical carbon chain

Erythro and Threowhen carbon chain is vertical, same (or analogous) substituents on same side of Fischer projection

CO2H

CH3

OH

OH

H

H

–9.5° +9.5°

CO2H

CH3

H

H

HO

HO

Erythro

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

+17.8° –17.8°

OH

CO2H

CH3

H

H

HO

CO2H

CH3

OHH

HHO

Threo

nonsuperimposable mirror images; enantiomers

trans-1-Bromo-1-chlorocyclopropane

Two Chirality Centers in a Ring

SSRR

nonsuperimposable mirror images; enantiomers

cis-1-Bromo-1-chlorocyclopropane


S R S R

stereoisomers that are not enantiomers; diastereomers

cis-1-Bromo-1-chloro-cyclopropane

trans-1-Bromo-1-chloro-cyclopropane


RSSS

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

Achiral Molecules withTwo Chirality Centers

CH3CHCHCH3

HO OH

32

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

2R,3R 2S,3S

chiral chiral

2R,3S

achiral

3 Stereoisomers of 2,3-Butanediol

2R,3R 2S,3S 2R,3S

chiral chiral achiral

CH3

CH3

OHH

HHOH OH

CH3

CH3

HHO H

CH3

CH3

OH

OHH


2R,3R 2S,3S

chiral chiral

these two areenantiomers


2R,3R 2S,3S

chiral chiral

CH3

CH3

OHH

HHOH OH

CH3

CH3

HHO


these two areenantiomers

2R,3S

the third structure is superimposable on itsmirror image


achiral

2R,3S

achiral

therefore, this structure and its mirror imageare the same

it is called a meso form

a meso form is an achiral molecule that has chirality centers


2R,3S

achiral

H

CH3

CH3

OH

OHHHHO

CH3

CH3

HHO


therefore, this structure and its mirror imageare the same

it is called a meso form

a meso form is an achiral molecule that has chirality centers

2R,3S

achiral

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

plane of symmetry is most common case

top half of molecule is mirror image of bottom half


2R,3S

achiral

H

CH3

CH3

OH

OHHHHO

CH3

CH3

HHO

A line drawnthe center ofthe Fischer projection of ameso formbisects it intotwo mirror-image halves.


Interactive QuestionDetermine the relationship between the

compounds shown below.

A) identicalB) enantiomersC) diastereomersD) meso

chiralmeso

There are three stereoisomers of 1,2-dichloro-cyclopropane; the achiral (meso) cis isomer and two enantiomers of the trans isomer.

Cyclic Compounds

RS R R

Maximum number of stereoisomers = 2n

where n = number of structural units capable of stereochemical variation

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

number is reduced to less than 2n if mesoforms are possible

Multiple Chirality Centers

4 chirality centers

16 stereoisomers

O

HOCH2CH—CH—CH—CHCH

OH OH OH OH

Example


How many chirality centers are in the molecule shown at the right?

A) 1

B) 2

C) 3

D) 4HO OH

H

H

HO

H3C

H

HCH2CH2CO2H

CH3

H

CH3

11 chirality centers

211 = 2048 stereoisomers

one is "natural" cholic acid

a second is the enantiomer of natural cholic acid

2046 are diastereomers of cholic acid

Cholic Acid (Figure 7.11)

Maximum number of stereoisomers = 2n

where n = number of structural units capable of stereochemical variation

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

number is reduced to less than 2n if mesoforms are possible

Multiple Chirality Centers

3-Penten-2-ol

HO H

E R

H OH

E S

HHO

Z R

H OH

SZ

How Many Stereoisomers?


(+)-Glucose has the Fischer projection shown. How many compounds are diastereomersof (+)-glucose?

A) 8

B) 14

C) 15

D) 16

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

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

C C + E—Y C CE Y

Reactions That ProduceDiastereomers

R

S

Anti addition to trans-2-butene gives meso diastereomer.

Bromine Addition to trans-2-Butene

Br2

meso

anti addition to trans-2-butene gives meso diastereomer

Bromine Addition to trans-2-Butene

R

S R

S

R

S

Anti addition to cis-2-butene gives racemic mixture of chiral diastereomers.

Bromine Addition to cis-2-Butene

Br2

50% 50%anti addition to cis-2-butene gives racemic mixture of chiral diastereomers

+

Bromine Addition to cis-2-Butene

R

R S

S

RCO3H

syn addition to trans-2-butene gives a racemic mixture of chiral diastereomers

50% 50%

Epoxidation of trans-2-Butene

R

R

+

S

S

syn addition to cis-2-butene gives the mesodiastereomer

RCO3H

meso

Epoxidation of cis-2-Butene

R

S R

S

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

related to mechanism: terms such assyn addition and anti addition refer tostereospecificity

Stereospecific Reaction .

trans-2-butene

cis-2-butene

trans-2-butene

cis-2-butene bromination anti 2R,3R + 2S,3S

bromination

epoxidation

epoxidation

anti

syn

syn

meso

meso

2R,3R + 2S,3S

Stereospecific reaction

a single starting material can give two or more

stereoisomeric products, but gives one of them

in greater amounts than any other

+

CH3

H

CH3

H

68% 32%

CH3

CH2

H

CH3

H

CH3

H

H2

Pt

Stereoselective ReactionInteractive Question

Which compound gives only a single stereoisomer of 1,3-dimethylcyclopentane on catalytic hydrogenation?

A) B)

C) D) both A and B

separation of a racemic mixture into its two enantiomeric forms

Resolution of Enantiomers enantiomers

C(+) C(-)

2P(+)

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

diastereomers

C(+)P(+)

C(-)P(+)

P(+)

P(+)

C(+)

C(-)

Strategy

Resolution of Enantiomers

• Amine salts are often used for resolution of carboxylic acids

Resolution of Enantiomers

• Use of a chiral amine leads to diastereotopic salts• Diastereomers have different physical properties and can thenbe separated

atactic

isotactic

syndiotactic

Stereoregular Polymers

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

• properties not very useful for fibers etc.

• formed by free-radical polymerization

Atactic Polypropylene

• stereoregular polymer; all methyl groups onsame side of main chain

• useful properties

• prepared by coordination polymerization under Ziegler-Natta conditions

Isotactic Polypropylene

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

• useful properties

• prepared by coordination polymerization under Ziegler-Natta conditions

Syndiotactic Polypropylene

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

Si Sid d

ab

c

ab

c

Chirality Centers on Other Atoms: Silicon

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

N N: :

ab

c

ab

c

very fast

Nitrogen Chirality Centers

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

P P: :

ab

c

ab

c

slow

Phosphorus

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

S S: :

ab

O_

ab

O_

slow

+ +

Sulfur in Sulfoxides

Summary: Chapter 7Summary: Chapter 7

7.1 Molecular Chirality: Enantiomers

7.2 The Chirality Center

7.3 Symmetry in Achiral Structures

7.4 Optical Activity

7.5 Absolute and Relative Configuration

7.6 Cahn-Ingold-Prelog Notation

7.7 Fischer Projections

7.8 Properties of Enantiomers

7.9 The Chirality Axis

Summary: Chapter 7Summary: Chapter 7

7.10 Reactions that Create a Chirality Center

7.11 Chiral Molecules with 2 Chirality Centers

7.12 Achiral Molecules with 2 Chirality Centers

7.13 Molecules with Multiple Chirality Centers

7.14 Diastereomers

7.15 Resolution of Enantiomers

7.16 Stereoregular Polymers

7.17 Chirality Centers other than Carbon

hougland che275 chapter7 slides

Documents

single chirality center

mirror plane

chirality centersa molecule

chirality centerchiral

chirality centercan

moleculesa plane of

symmetry tests

planeof symmetry