Download - 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
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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 , ….
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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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Fischer projections can be rotated according to certain rules
180 o
same as
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Fischer projections can be rotated according to certain rules
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
" "
" "
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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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