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Created byProfessor William Tam & Dr. Phillis Chang
Chapter 5
StereochemistryChiral Molecules
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
1. Chirality & Stereochemistry
v An object is achiral (not chiral) if the object and its mirror image are identical
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v A chiral object is one that cannot be superposed on its mirror image
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2. Isomerisom: ConstitutionalIsomers & Stereoisomers
v Isomers: different compounds that have the same molecular formula● Constitutional isomers: isomers
that have the same molecular formula but different connectivity –their atoms are connected in a different order
2A. Constitutional Isomers
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v Examples
andButane 2-Methylpropane
MolecularFormula
ClCl
and1-Chloropropane 2-Chloropropane
ConstitutionalIsomers
C4H10
C3H7Cl
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v ExamplesMolecularFormula
and
Butanoic acid Methyl propanoate
OH OCH3
O
O
ConstitutionalIsomers
C2H6O
C4H8O2
OH CH3 O CH3andEthanol Methoxymethane
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
2B. Stereoisomers
v Stereoisomers are NOT constitutional isomers
v Stereoisomers have their atoms connected in the same sequence but they differ in the arrangement of their atoms in space. The consideration of such spatial aspects of molecular structure is called stereochemistry
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2C. Enantiomers & Diastereomersv Stereoisomers can be subdivided into
two general categories:enantiomers & diasteromers● Enantiomers – stereoisomers
whose molecules are nonsuperimposable mirror images of each other
● Diastereomers – stereoisomers whose molecules are not mirror images of each other
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v Geometrical isomers (cis & trans isomers) are:● Diastereomers
e.g.
(trans)Ph PhPh Ph
(cis)and
Cl
H
Cl
H
H
Cl
Cl
H(trans)(cis)
and
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Subdivision of IsomersIsomers
(different compounds with same molecular formula)
Constitutional Isomers(isomers whose atoms
have a different connectivity)
Stereoisomers(isomers that have the same
connectivity but differ in spatial arrangement of their atoms)
Enantiomers(stereoisomers that are
nonsuperimposable mirrorimages of each other)
Diastereomers(stereoisomers that areNOT mirror images of
each other)
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3. Enantiomers and Chiral Molecules
v Enantiomers occur only with compounds whose molecules are chiral
v A chiral molecule is one that is NOTsuperimposable on its mirror image
v The relationship between a chiral molecule and its mirror image is one that is enantiomeric. A chiral molecule and its mirror image are said to be enantiomers of each other
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OH (2-Butanol)
OHH
(I)
HO H
(II)
(I) and (II) arenonsuperimposablemirror images ofeach other
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© 2014 Pearson Education, Inc.
Different Conformations
Compounds with different conformations (conformers) cannot be separated.
© 2014 Pearson Education, Inc.
Different Configurations
Compounds with different configurations can be separated.
Cis–trans isomers have different configurations.
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4. Molecules Having One ChiralityCenter Are Chiral
v A chirality center is a tetrahedral carbon atom that is bonded to four different groups
v A molecule that contains one chirality center is chiral and can exist as a pair of enantiomers
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v The presence of a single chirality center in a molecule guarantees that the molecule is chiral and that enantiomeric forms are possible
v An important property of enantiomers with a single chirality center is that interchanging any two groups at the chirality center converts one enantiomer into the other
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v Any atom at which an interchange of groups produces a stereoisomer is called a stereogenic center (if the atom is a carbon atom it is usually called a stereogenic carbon)
v If all of the tetrahedral atoms in a molecule have two or more groups attached that are the same, the molecule does not have a chirality center. The molecule is superimposable on its mirror image and is achiral
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Asymmetric Center versusStereocenter
Asymmetric (chiral) center: an atom attached to four different groups
Stereocenter: an atom at which the interchange of two groups produces a stereoisomer
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Me EtClH
(III)
CH
EtMeCl*
mirror
MeEtCl H
(IV)
(III) and (IV) are nonsuperimposablemirror images of each other
sameas
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CH
MeMeCl
mirror
sameas
(V) and (VI) are superimposable⇒ not enantiomers ⇒ achiral
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4A. Tetrahedral vs. TrigonalStereogenic Centers
v Chirality centers are tetrahedral stereogenic centers
Me EtOHH
*(A)
mirror
MeEtHO H
*(B)
Tetrahedral stereogenic center⇒ chiral
(A) & (B) areenantiomers
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(C)H
Ph
Ph
H
mirror(D)
Ph
H
H
Ph
Trigonal stereogenic center⇒ achiral (C) & (D) are identical
v Cis and trans alkene isomers contain trigonal stereogenic centers
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5. More about the BiologicalImportance of Chirality
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(R)-ibuprofen (S)-ibuprofen
Inactive Active analgesic & anti-inflammatory agent
v The activity of drugs containing chirality centers can vary between enantiomers, sometimes with serious or even tragic consequences
v For several years before 1963 thalidomide was used to alleviate the symptoms of morning sickness in pregnant women
Thalidomide
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v In 1963 it was discovered that thalidomide (sold as a mixture of both enantiomers) was the cause of horrible birth defects in many children born subsequent to the use of the drug
Thalidomide
NNH
O
OO
O
NNH
O
OO
Oenantiomer ofThalidomide
(causes birth defects)(cures morning sickness)
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Thalidomide
N
O
O
N
O
O
H
HN
O
O
N
O
O
H
H
(R) -ThalidomideSedative and Hypnotic
(S)-ThalidomideTeratogen
Birth Defects
● One enantiomer is a bronchodilator, the other inhibits platelet aggregation
NH
OMe
OMeOMe
HO
HO
Tretoquinol
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v 66% of all drugs in development are chiral, 51% are being studied as a single enantiomer
v Of the $475 billion in world-wide sales of formulated pharmaceutical products in 2008, $205 billion was attributable to single enantiomer drugs
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
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Biological MoleculesRULE - Enzymes are chiral reagents because their binding site is chiral
Biological Discrimination
6. How to Test for Chirality:Planes of Symmetry
v A molecule will not be chiral if it possesses a plane of symmetry
v A plane of symmetry (mirror plane) is an imaginary plane that bisects a molecule such that the two halves of the molecule are mirror images of each other
v All molecules with a plane of symmetry in their most symmetric conformation are achiral
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
Me Me
Cl
H
Me Et
Cl
H
Plane of symmetry
No plane of symmetry
achiral
chiralCopyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
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Symmetry tests for achiral structures
Any molecule with a plane or center of symmetrymust be achiral.
Plane of symmetry Center of symmetry
7. Naming Enantiomers:The R,S -System
v Using only the IUPAC naming that we have learned so far, these two enantiomers will have the same name:● 2-Butanol
v This is undesirable because each compound must have its own distinct name
OHH
(I)
HO H
(II)
OHRecall:
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11
v Rule 1● Assign priorities to the four different
groups on the stereocenter from highest to lowest (priority bases on atomic number, the higher the atomic number, the higher the priority)
7A. How to Assign (R) and (S)Configurations
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v Rule 2● When a priority cannot be assigned
on the basis of the atomic number of the atoms that are directly attached to the chirality center, then the next set of atoms in the unassigned groups is examined. This process is continued until a decision can be made.
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v Rule 3● Visualize the molecule so that the
lowest priority group is directed away from you, then trace a path from highest to lowest priority. If the path is a clockwise motion, then the configuration at the asymmetric carbon is (R). If the path is a counter-clockwise motion, then the configuration is (S)
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CH2
CH3C
O HStep 2: CH3
v Example HO H (2-Butanol)
①
③
④
② or ③ ② or ③CC
O HStep 1:
① ④
②
(H, H, H) (C, H, H)
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OH
EtMe
①
④
②③
OH
EtMe
H
OH
EtMe EtMe
HO H=
OH
EtMe
H
Arrows are clockwise
(R)-2-ButanolCopyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
13
OCH3
H3C CH2CH3Br
v Other examples①
④
②
③
Cl
H CH3HO
Cl
CH3HO
Counter-clockwise
(S)
①
④
②
③
OCH3
CH2CH3Br
Clockwise
(R)
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Cl
H OHBr
Cl
Br HHO
v Other examples
①
④
②
③
Cl
OHBr
Clockwise
(R)
● Rotate C–Cl bond such that H is pointed to the back
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OCH3
H IH3C
H
I OCH3H3C
v Other examples
①④
②
③
OCH3
IH3C
● Rotate C–CH3 bond such that H is pointed to the back
Counter-clockwise
(S)Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
14
1
23
4
S-configuration
v Rule 4● For groups containing double or
triple bonds, assign priorities as if both atoms were duplicated or triplicatede.g. C O C
OOC
as
C C CC
CC
as
C C CC
CCC
asC
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v Example CH3
H CH=CH2HO①
④ ②
③
(S)
CH3 CH CH2
CH
CCC
HH
CH3
CH CH2
Compare & :
equivalent to
Thus, Þ (H, H, H)
Þ (C, C, H)CH CH2
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v Other examplesOH
HCl
CH3
O①
④
②
③
(R)
H2C
HCl
CH3
O
OH
①
④②
③
(S)
C Þ (O, O, C)
C Þ (O, H, H)
②
③
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Quiz 1 Quiz 2
Quiz 3
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Quiz 4
Which one is (S)-enantiomer?
A B
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8. Properties of Enantiomers:Optical Activity
v Enantiomers● Mirror images that are not
superimposable
mirror
H3CH2C
*CH3
H
ClCH2CH3
*H3C
H
Cl
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v Enantiomers have identical physical properties (e.g. melting point, boiling point, refractive index, solubility etc.)
Compound bp (oC) mp (oC)(R)-2-Butanol 99.5(S)-2-Butanol 99.5(+)-(R,R)-Tartaric Acid 168 – 170(–)-(S,S)-Tartaric Acid 168 – 170(+/–)-Tartaric Acid 210 – 212
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v Enantiomers● Have the same chemical properties
(except reaction/interactions with chiral substances)
● Show different behavior only when they interact with other chiral substances
● Rotate plane-polarized light in opposite direction
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v Optical activity● The property possessed by chiral
substances of rotating the plane of polarization of plane-polarized light
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v The electric field (like the magnetic field) of light is oscillating in all possible planes
v When this light passes through a polarizer (Polaroid lens), we get plane-polarized light (oscillating in only one plane)
Polaroidlens
8A. Plane-Polarized Light
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v A device for measuring the optical activity of a chiral compound
8B. The Polarimeter
a =observed optical rotation
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8C. Specific Rotation
D[a] =
25 ac x
temperatureobserved rotation
wavelength of light(e.g. D-line of Na lamp,l=589.6 nm)
concentration of sample solutionin g/mL
length of cellin dm(1 dm = 10 cm)
ℓ
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Calculate [a]Dv A 1.00-g sample is dissolved in 20.0 mL ethanol. 5.00 mL of this
solution is placed in a 20.0-cm polarimeter tube at 25°C. The observed rotation is 1.25° counterclockwise.
Concentration ing/mL.
Length in decimeter
oo
c5.12
0.100.20
0.2000.1
25.1 l
(observed) ][ 25D -=
·÷øö
çèæ
-=
·=aa
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v The value of a depends on the particular experiment (since there are different concentrations with each run) ● But specific rotation [a] should be
the same regardless of the concentration
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v Two enantiomers should have the same value of specific rotation, but the signs are opposite
mirror
HO
*CH2CH3
CH3
H
[a] = + 13.5o25
D
OH
*H3CH2C
CH3
H
[a] = - 13.5o25
D
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9. The Origin of Optical Activity
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v An equimolar mixture of two enantiomers is called a racemic mixture (or racemateor racemic form)
v A racemic mixture causes no net rotation of plane-polarized light
9A. Racemic Forms
HC2H5
CH3OH
(R)-2-Butanol
HC2H5
H3CHO
(S)-2-Butanol(if present)
rotation
equal & opposite rotation by the enantiomer
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v A sample of an optically active substance that consists of a single enantiomer is said to be enantiomerically pure or to have an enantiomeric excess of 100%
9B. Racemic Forms and EnantiomericExcess
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v An enantiomerically pure sample of (S)-(+)-2-butanol shows a specific rotation of +13.52
D[a] = +13.52
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v A sample of (S)-(+)-2-butanol that contains less than an equimolar amount of (R)-(–)-2-butanol will show a specific rotation that is less than 13.52 but greater than zero
v Such a sample is said to have an enantiomeric excess less than 100%
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v Enantiomeric excess (ee)● Also known as the optical purity
% enantiomericexcess *
observed specific rotationspecific rotation of the
pure enantiomers
= x 100
● Can be calculated from optical rotations
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v Example● A mixture of the 2-butanol
enantiomers showed a specific rotation of +6.76. The enantiomeric excess of the (S)-(+)-2-butanol is 50%
% enantiomericexcess *
+6.76+13.52= x 100 = 50%
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10. The Synthesis of Chiral Molecules
10A. Racemic Forms
O
CH3CH2CCH3 H H ( )-CH3CH2CHCH3+-
OH
+ Ni
Butanone(achiral
molecules)
Hydrogen(achiral
molecules)
( )-2-Butanol(chiral
molecules; but50:50 mixture
(R) & (S))
+-
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10B. Stereoselective Synthesesv Stereoselective reactions are reactions
that lead to a preferential formation of one stereoisomer over other stereoisomers that could possibly be formed● enantioselective – if a reaction
produces preferentially one enantiomer over its mirror image
● diastereoselective – if a reaction leads preferentially to one diastereomer over others that are possible
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
+-
OEt
O
FOH
O
F+ EtOH
H+, H2Oheat
racemate ( ) +-racemate ( )
+-
OEt
O
FOH
O
F
+ EtOH
H2Olipase
racemate ( ) (-)(> 69% ee)
OEt
O
F(+)
(> 99% ee)
+
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
11. Chiral Drugsv Of the $475 billion in world-wide sales of
formulated pharmaceutical products in 2008, $205 billion was attributable to single enantiomer drugs
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
Singulair(asthma and allergy treatment)
Naproxen(anti-inflammatory drug)
MeO
CH3
CO2H
N
HO CH3
CH3S
NaO2C
Cl
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22
Through The Looking-Glass (1872)
v Lewis Carrollv His work may have been affected
by Louis Pasteur
“Maybe Looking-glass milk isn’t good to drink.” Alice
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What if Alice had a headache? If she found bottles of acetylsalicylic acid (Aspirin), acetaminophen (Tylenol), naproxen (Aleve), and ibuprofen (Advil, racemic), which pills shouldn’t she take?
12. Molecules with More than OneChirality Center
v In compounds with n tetrahedral stereocenters, the maximum number of stereoisomers is 2n
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FINDING STEREOCENTERS (CHIRAL CARBONS)
CH3
CH3
HO
H
CH3
CH3
CH3
**
**
*
* *
*
n = 8
28 = 256
12A. How to Draw Stereoisomers forMolecules Having More than OneChirality Center
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v Start by drawing the portion of the carbon skeleton that contains the chirality centers in such a way that as many of the chirality centers are placed in the plane of the paper as possible, and as symmetrically as possible
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v Next we add the remaining groups that are bonded at the chirality centers in such a way as to maximize the symmetry between the chirality centers
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v To draw the enantiomer of the first stereoisomer, we simply draw its mirror image
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v To draw another stereoisomer, we interchange two groups at any one of the chirality centers• All of the possible stereoisomers for a
compound can be drawn by successively interchanging two groups at each chirality center
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v Next we examine the relationship between all of the possible pairings of formulas to determine which are pairs of enantiomers, which are diastereomers
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v Structures 1 and 2 are enantiomers; structures 3 and 4 are also enantiomers
v Structures 1 and 3 are stereoisomers and they are not mirror images of each other. They are diastereomers• Diastereomers have different physical
properties - different melting points and boiling points, different solubilities, and so forth
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25
v Diastereomers● Stereoisomers that are not
enantiomers
● Unlike enantiomers, diastereomersusually have substantially different chemical and physical properties
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C HC H
CH3
ClBr
HOCHCH
CH3
ClBr
OH(I) (II)
C HC H
HO
ClBr
CH3
CHCH
OH
ClBr
CH3(III) (IV)
v (I) & (II) are enantiomers of each otherv (III) & (IV) are enantiomers of each
otherCopyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
C HC H
CH3
ClBr
HOCHCH
CH3
ClBr
OH(I) (II)
C HC H
HO
ClBr
CH3
CHCH
OH
ClBr
CH3(III) (IV)
v Diastereomers of each other:● (I) & (III), (I) & (IV), (II) & (III),
(II) & (IV) Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
12B. Meso Compoundsv Compounds with two stereocenters do
not always have four stereoisomers (22 = 4) since some molecules are achiral (not chiral), even though they contain stereocenters
v For example, 2,3-dichlorobutane has two stereocenters, but only has 3 stereoisomers (not 4)
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26
C BrC Br
H
CH3
H
CH3
CBrCBr
H
CH3
H
CH3(I) (II)
C BrC Br
CH3
CH3
H
HCBrCBr
CH3
CH3
H
H(III) (IV)
Note: (III) contains a plane of symmetry, is a meso compound, and is achiral([a] = 0o).
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C BrC Br
H
CH3
H
CH3
CBrCBr
H
CH3
H
CH3(I) (II)
C BrC Br
CH3
CH3
H
HCBrCBr
CH3
CH3
H
H(III) (IV)
v (I) & (II) are enantiomers of each other and chiral
v (III) & (IV) are identical and achiralCopyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
C BrC Br
H
CH3
H
CH3
CBrCBr
H
CH3
H
CH3(I) (II)
C BrC Br
CH3
CH3
H
HCBrCBr
CH3
CH3
H
H(III) (IV)
v (I) & (III), (II) & (III) are diastereomersv Only 3 stereoisomers:
● (I) & (II) {enantiomers}, (III) = (IV) {meso}
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12C. How to Name Compounds withMore than One Chirality Center
v 2,3-Dibromobutane
● Look through C2–Ha bond
HbBrHa Br
1
2 3
4
C C
Br Ha
12
3
(H, H, H) (Br, C, H)
①④
②③C2: (R) configuration
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27
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
C C
Br Hb
23
4
(H, H, H) (Br, C, H)
● Look through C3–Hb bond
CH3
Ha HbBr
CH3
Br1
23 4
①④
②③
C3: (R) configuration
● Full name:t (2R, 3R)-2,3-Dibromobutane
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13. Fischer Projection Formulas13A. How To Draw and Use Fischer
Projections
H3C
Ph
COOH
HOEt Br
Et OH
Br Ph
CH3
COOH
Et OH
Br Ph
CH3
COOH
FischerProjection
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Ph
H
COOH
HMe OH
Me H
HO H
Ph
COOH
Me H
HO H
Ph
COOH
FischerProjection
PhCOOH
H Me
OHH
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28
H3C
Cl
CH3
HCl H
(I)(2S, 3S)-Dichlorobutane
Cl H
H Cl
CH3
CH3
CH3
Cl
H3C
HClH
(II)(2R, 3R)-Dichlorobutane
H Cl
Cl H
CH3
CH3
enantiomers
v (I) and (II) are both chiral and they are enantiomers of each other
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H3C
Cl
CH3
ClH H
(III)(2S, 3R)-Dichlorobutane
H Cl
H Cl
CH3
CH3
v (III) is achiral (a meso compound)v (III) and (I) are diastereomers of each
other
Plane ofsymmetry
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14. Stereoisomerism of CyclicCompounds
Me
H Me
H Me
H Me
H
mirror
enantiomers
H
Me Me
H
Plane ofsymmetry
a meso compoundachiral
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14A. Cyclohexane Derivatives
Me
Me
Me
Me
v 1,4-DimethylcyclohexanePlane of
symmetry
HMe
MeH
HMe
HMe
cis-1,4-dimethylcyclohexane
trans-1,4-dimethylcyclohexane
• Both cis- & trans-1,4-dimethylcyclo-hexanes are achiral and optically inactive
• The cis & transforms are diastereomers
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29
Me Me**
cis-1,3-dimethylcyclohexane
v 1,3-DimethylcyclohexanePlane of
symmetry
(meso)
H
Me
HMe
● cis-1,3-Dimethylcyclohexane has a plane of symmetry and is a meso compound
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
Me Me**
trans-1,3-dimethylcyclohexane
v 1,3-Dimethylcyclohexane
NO plane of symmetry
enantiomers
H
Me
MeH
H
Me
MeH
● trans-1,3-Dimethylcyclohexane exists as a pair of enantiomers
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v 1,3-Dimethylcyclohexane● Has two chirality centers but only
three stereoisomers
(meso)
H
Me
HMe
cis-1,3-dimethylcyclohexane
enantiomers
H
Me
MeH
H
Me
MeH
trans-1,3-dimethylcyclohexane
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v 1,2-Dimethylcyclohexane
enantiomers
H
HMe
MeH
HMe
Me
● trans-1,2-Dimethylcyclohexane exists as a pair of enantiomers
mirror
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
30
v 1,2-Dimethylcyclohexane● With cis-1,2-dimethylcyclohexane
the situation is quite complicated
Me
HMe
HMe
HMe
H
(I) (II)
● (I) and (II) are enantiomers to each other
mirror
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved. Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v If equilibrium exists between two chiral conformers, molecule is not chiral.
v Judge chirality by looking at the most symmetrical conformer.
v Cyclohexane can be considered to be planar, on average.
© 2014 Pearson Education, Inc.
Meso Compounds….but the boat conformation does have this plane of symmetry
RULE - as long as one conformation of a compound has a plane of symmetry, the compound will be achiral (meso if there are 2+ asymmetric centers):
In order to see the symmetry with 2,3-dibromobutane, we had to look at the eclipsed (unstable) conformation © 2014 Pearson Education, Inc.
31
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
15. Relating Configurations throughReactions in Which No Bonds tothe Chirality Center Are Broken
v A reaction is said to proceed with retention of configuration at a chirality center if no bonds to the chirality center are broken. This is true even if the R,S designation for the chirality center changes because the relative priorities of groups around it changes as a result of the reaction
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
H
O
Me H
HOH
Me H HNaBH4MeOH
Ph Br
NaCNDMSO
Me HPh CN
Me H
Same configuration
Same configurationCopyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
15A. Relative & Absolute Configurationsv Chirality centers in different molecules have
the same relative configuration if they share three groups in common and if these groups with the central carbon can be superimposed in a pyramidal arrangement
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
32
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
Reactions of Compounds that Contain an Asymmetric Carbon
The reactant and the product have the same relative configuration because the reaction does not break any of the bonds to the asymmetric carbon.
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v The absolute configuration of a chirality center is its (R) or (S) designation, which can only be specified by knowledge of the actual arrangement of groups in space at the chirality center(R)-2-Butanol (S)-2-Butanol
HO H H OH
enantiomersCopyright © 2016 by John Wiley & Sons, Inc. All rights reserved. Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
33
16. Separation of Enantiomers:Resolution
e.g.R R'
OH
*(racemic)
Cl OMeO
Ph CF3
(Mosher acidchloride)
R R'
O
OOMe
PhCF3
R R'
O
OOMe
PhCF3+
( 1 : 1 )diastereomers
usually separable either by flash column
chromatography or recrystallization etc.
v Resolution – separation of two enantiomers
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v Kinetic Resolution
R2
R1R
OH
*R2
R1R
OH
*R2
R1R
OH
*O
+
(racemic)
● One enantiomer reacts “fast” and another enantiomer reacts “slow”
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
v e.g.Me3Si
C5H11
OH*
(racemic)
tBuOOH, Ti(OiPr)4
(-)-DET
Me3Si
C5H11
OH
Me3Si
C5H11
OHO+
42%(99%ee)
43%(99%ee)
Me3Si
OHR'
H
Me3Si
OHH
R'
´
S R
ü
* stop reaction at £ 50%* maximum yield = 50%
(-)-DET:COOEt
COOEtHO
HO
(D)-(-)-Diethyl Tartrate
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
17. Compounds with ChiralityCenters Other than Carbon
R1Si
R2
R4 R3
R1Ge
R2
H R3
R1N
R2
R4 R3X S
R2 R1
O
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
34
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18. Chiral Molecules That Do NotPossess a Chirality Center
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35
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
enantiomers
C CCl
HC
Cl
HCC
Cl
HC
Cl
H
mirror
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.
The only definitive test for chirality is to take the mirror image of the molecule and check if it willsuperimpose :
chiral = mirror image doesnt superimposeachiral = mirror image does superimpose
It doesn’t matter if you recognize any stereocentersor not ! The entire molecule can be chiral !
TESTING FOR CHIRALITY
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