Ch5 Stereochemistry Winter 2015 2

8/9/2019 Ch5 Stereochemistry Winter 2015 2

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CHEM 138 HProf. M. Winnik

[email protected] LM520

• Stereochemistry (Chapter 5)• Organic reactivity (Chapter 6)• Alkenes: Structure & Reactivity (Chapter 7)• Alkenes: more reactions (Chapter 8)

McMurry 8 th Ed

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Chapter 5 Stereochemistry

with thanks to Mark Nitz and Kris Quinlan

McMurry 8 th Ed

Recognizing the stereochemistry of double bonds and E,Z notationwill be on TT1.

Recognizing the stereochemistry of chiral centres and R,S notationwill be on TT1.

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CHM 138 HStereochemistry

Chapter 5, excluding 5.10

Chapter 25, 25.2 only

McMurry, 8th edition

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Isomers Different compounds with the same molecular formula

Constitutional isomers:

isomers with differentatomic connectivities

Stereoisomers: isomerswith the same atomicconnectivity but withdifferent geometries

O

OH

H

Br

H

Br

H

Br

Br

H

In Ch. 5, we examine stereoisomers that are not superimposibleon their mirror image. 4


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mirror

The mirror image:

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Chirality = "handedness"

your handsare chiral!

objects that do not have amirror plane are CHIRAL

objects that contain amirror plane are ACHIRAL

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Some molecules are achiral, some are chiral:

An achiral molecule:

mirror plane

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an achiralmolecule

an achiralmolecule

a chiralmolecule

a chiralmolecule

Some molecules are achiral, some are chiral:

constitutional isomers

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Properties of chiral objects

A chiral object and its mirror imagecannot be superimposed

chiral: cannot be superimposed

achiral: can be superimposed

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Chiral molecules and their non-superimposablemirror images are called “enantiomers”

chiral

enantiomers

The source of chirality is the carbon atom with 4 different substituents:

chirality centre

called a "chirality centre" or "stereocentre"

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molecules with chiral centres cannot be superimposedon one another

alanine: an amino acid


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Biology is full of chiral molecules

alanine:

sucrose (table sugar):

chiral

chiral

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Which of the following drugs is/are chiral?

Where are the centres of chirality?

Aspirin Tylenol Advil

(acetaminophen) (ibuprofen)

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if you have 2 identical substituents on an atom it can’tbe a chirality centre

chirality centre


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melting point:

So how can enantiomers be differentiated from each other?

2. optical activity

1. interactions with other chiral molecules/environments

– 112 oC 91 oC 1.255 g/mL

S R

e.g. 2-bromobutane

density:boiling point:

Enantiomers have identical physical properties

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1. interactions with other chiral molecules/environments

E.g. many biological receptor sites are chiral – will only“accept” one particular enantiomer of a substance

- biological molecules often have differenttastes, smells, toxicities

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2. optical activity

chiral molecules areoptically active –

they rotate plane-polarized light

plane-polarizedlight is chiral

one enantiomer rotates light tothe right = (+) or d-enantiomer

other enantiomer rotates light tothe left = ( ) or l-enantiomer

(S )-(+)-lactic acid ( R )-( – )-lactic acid

observeranalyzerpolarizer sample tubelight

source

unpolarizedlight

polarizedlight

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Specific rotation , [ ]D

, of a chiral compound is a measure of its

optical activity:

[ ]D =C L

Any two enantiomers have equal and opposite [ ] D values:

[ ]D ((R )-( –)-lactic acid) = – 3.82 o [ ]D ((S )-(+ )-lactic acid) = +3.82 o

Characteristic property of a chiral compound:

optically active compounds must be chiral

L = path length (dm) C = concentration (g/mL)

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probably won’t be tested in depth but know that it isa property of enantiomers


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alanine

Indicating chirality

- how to indicate the different configuration of substituentsaround each chirality centre?

1. Identify the chirality centre you wish to assign

e.g. 2-bromobutane

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2. Determine the priorities ofattached groups

1

2

3

4

3. Rotate molecule to put thelowest priority group at the back

2

1

3

H at the back behind C

the Cahn-Ingold-Prelog rules

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LEFT HAND TURN(ANTI-CLOCKWISE)

2-bromobutane 1

2 3

Its enantiomer:

(S )-

1

2 3 RIGHT HAND TURN(CLOCKWISE)

2-bromobutane (R )-

“R ” and “ S ” are the (absolute) configurations of a chirality centre

4. Determine direction from 1st to 2nd to 3rd priority groups

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Easy Way to Remember R and S

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2

2

3 3

RS20


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Review: Determining group priorities:the Cahn-Ingold-Prelog rules

1. Rank atoms attached to the chirality centre indecreasing atomic number

Br > Cl > F > O > N > C … > H

1 4

2. If the first atoms in the group are the same,look at the 2 nd , the 3 rd , the 4 th , ….

4

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3. Multiply-bonded atoms equivalent to same number of singlebonded atoms

When you see: prioritize using:

When you see: prioritize using:

3 4

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3R

Iodine has greatest atomic number,but we have to look at the atomsattached to the chiral centre

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3

S

4

1 2


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E,Z and R,S will be on TT1

Let's try some examples

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both C2 and C3 can be either R or S

threonine - two stereocentres

Molecules with >1 chirality centre

Four stereoisomers are possible:

For n chirality centres, a maximum of 2 n stereoisomers exist.

2 3

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

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H (4)

Br (1)

F (2)

CH3(3)

S

H (4)CH3 (3)

Br (1)

CH2CH3 (2)

S

O=CH(2)

HO(3)

H (4)

C=OOH (1)

S(looking at it from theC pointed to)

whenever a N is next to an sp2carbon, it becomes planarit wants for its orbitals to overlap

those of the double bond

1

E

chiral centre: has 4 diffsubstituents, can’t besp2

a chiral centreH

1 2

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S


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S S R R

S R S R

enantiomers

enantiomers

The four possible stereoisomers

enantiomers – must have oppositeconfiguration at ALL chirality centres

diastereomers - configuration not opposite at all chirality centres

- "non-mirror images"

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S

R

S S

RS

S

- diastereomeric salts different solubilities

Diastereomers have different physical and chemical properties

e.g. boiling point, spectra, solubility, etc.....

racemic mixture

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E.g. tartaric acid

= meso compound

A molecule can have chirality centres but still be achiral

RS

RSmeso compounds havean internal mirror plane

RS

The molecule and its mirror image are superimposable = achiral

RRSS

Its other two stereoisomersare enantiomers

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Fischer Projections (text p. 975)

C

COOH

CH 3H

HO

CHO H

COOH

CH 3

COOH

H

CH 3

HO

Central C atom is not shownVertical lines – go into the pageHorizontal lines – come out of the page

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1852-1919

Emil Fischer

Fischer died long before R and S notation was invented. Heneeded a way of depicting stereochemistry in molecules with2 or more adjacent chiral centers.

One chiral center:

The molecule is drawn flat

Normally, the longestcarbon chain is

vertical.


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Fischer projections (Section 25.2)

Fischer represented chirality centres differently:

Fischerprojection

1852-1919

Emil Fischer

horizontal linesout of the page

the moleculeappears flat

central C atom

is not shown

vertical linesinto the page

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- two (or more) chirality centres:

R,R tartaric acid

normally, the longestcarbon chain isdrawn vertically

R

RCOOH

COOH

OH

HO H

Hrotate

the vertical line connecting the two middlechirality centres lies in the plane of the page

all other vertical lines go into the page

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Fischer projections can be rotated according to certain rules

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180 o

same as


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180 o

same as

keeping one group fixedand rotating the others

How are Fischer projections useful?

- helpful for visualizing molecules withtwo or more chirality centres

e.g. sugars and sugar derivatives

CH=O

OH

OH

OH

HO

H

H

H

H

CH2OH

by convention, the carbon with thehigher oxidation state is put at the top

D-glucose

COOH

COOH

OH

HO H

H

- it is easy to draw mirror images COOH

COOH

H

H OH

HO

R,R

tartaric acid

S,S34


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Prochirality

An achiral molecule is prochiral if, in a single chemical step,

it can be converted into a chiral product .

H2

2-butanone 2-butanol

prochiral chiral

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H2

2-butanone has prochiral faces:

2-butanone

prochiral

“re” and “ si ” refer to the

reactant, NOT the product

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Stereochemical Result of Prochirality


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or

si face

re faceH

H

Stereochemical Result of Prochirality

“re” and “ si ” refer to the reactant and NOT the product!!

Defining pro-R and pro-S substituents:

1. Raise the priority of the atom of interest over the other(identical) atom without changing the priority relative tothe other substituents

2. Use the usual method to determine the configuration ofthe chirality center

prochiral centre

pro-R pro-S

" "

" "

12

3 4

Prochiral centre:

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Summary isomersconstitutionalisomers

enantiomers

same atom connectivitystereoisomers

diastereomers mesocompounds

configurational

diastereomers

cis - trans

diastereomers

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Ch5 Stereochemistry Winter 2015 2