created by professor william tam & dr. phillis chang chapter 5 stereochemistry chiral molecules...
TRANSCRIPT
Created byProfessor William Tam & Dr. Phillis
ChangCopyright © 2014 by John Wiley & Sons, Inc. All rights reserved.
Chapter 5
StereochemistryChiral Molecules
© 2014 by John Wiley & Sons, Inc. All rights reserved.
About The Authors
These Powerpoint Lecture Slides were created and prepared by Professor William Tam and his wife Dr. Phillis Chang.
Professor William Tam received his B.Sc. at the University of Hong Kong in 1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard University (USA). He joined the Department of Chemistry at the University of Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and Associate Chair in the department. Professor Tam has received several awards in research and teaching, and according to Essential Science Indicators, he is currently ranked as the Top 1% most cited Chemists worldwide. He has published four books and over 80 scientific papers in top international journals such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem.
Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She lives in Guelph with her husband, William, and their son, Matthew.
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Table of Contents (hyperlinked)1. Chirality and Stereochemistry2. Isomerism: Constitutional Isomers and Stereoisomers3. Enantiomers and Chiral Molecules4. Molecules Having One Chirality Center Are Chiral5. More about the Biological Importance of Chirality6. How to Test for Chirality: Planes of Symmetry7. Naming Enantiomers: The R,S-System8. Properties of Enantiomers: Optical Activity9. The Origin of Optical Activity10. The Synthesis of Chiral Molecules11. Chiral Drugs12. Molecules with More than One Chirality Center13. Fischer Projection Formulas14. Stereoisomerism of Cyclic Compounds15. Relating Configurations through Reactions in Which
No Bonds to the Chirality Center Are Broken16. Separation of Enantiomers: Resolution17. Compounds with Chirality Centers Other than Carbon18. Chiral Molecules That Do Not Possess a Chirality Center
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Table of Contents1. Chirality and Stereochemistry2. Isomerism: Constitutional Isomers and Stereoisomers3. Enantiomers and Chiral Molecules4. Molecules Having One Chirality Center Are Chiral5. More about the Biological Importance of Chirality6. How to Test for Chirality: Planes of Symmetry7. Naming Enantiomers: The R,S-System8. Properties of Enantiomers: Optical Activity9. The Origin of Optical Activity10. The Synthesis of Chiral Molecules11. Chiral Drugs12. Molecules with More than One Chirality Center13. Fischer Projection Formulas14. Stereoisomerism of Cyclic Compounds15. Relating Configurations through Reactions in Which No
Bonds to the Chirality Center Are Broken16. Separation of Enantiomers: Resolution17. Compounds with Chirality Centers Other than Carbon18. Chiral Molecules That Do Not Possess a Chirality Center
© 2014 by John Wiley & Sons, Inc. All rights reserved.
In this chapter we will consider:
How to identify, codify, and name the three-dimensional arrangement of atoms and molecules
How such arrangements can lead to unique properties and behaviors
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1. Chirality & Stereochemistry
An object is achiral (not chiral) if the object and its mirror image are identical
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A chiral object is one that cannot be superposed on its mirror image
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1A.The Biological Significance ofChirality
Chiral molecules are molecules that cannot be superimposed onto their mirror images
Thalidomide
NNH
O
OO
O
● One enantiomer causes birth defects, the other cures morning sickness
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● One enantiomer is a bronchodilator, the other inhibits platelet aggregation
NH
OMe
OMeOMe
HO
HO
Tretoquinol
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66% of all drugs in development are chiral, 51% are being studied as a single enantiomer
Of the $475 billion in world-wide sales of formulated pharmaceutical products in 2008, $205 billion was attributable to single enantiomer drugs
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2. Isomerisom: ConstitutionalIsomers & Stereoisomers
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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Examples
andButane 2-Methylpropane
MolecularFormula
ClCl
and1-Chloropropane 2-Chloropropane
ConstitutionalIsomers
C4H10
C3H7Cl
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Examples
MolecularFormula
and
Butanoic acid Methyl propanoate
OHOCH3
O
O
ConstitutionalIsomers
C2H6O
C4H8O2
OH CH3 O CH3andEthanol Methoxymethane
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2B.Stereoisomers
Stereoisomers are NOT constitutional isomers
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 & Diastereomers 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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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 Isomers
Isomers(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 mirror
images of each other)
Diastereomers(stereoisomers that areNOT mirror images of
each other)
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3. Enantiomers and Chiral Molecules
Enantiomers occur only with compounds whose molecules are chiral
A chiral molecule is one that is NOT superimposable on its mirror image
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) arenonsuperimposa
blemirror images ofeach other
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4. Molecules Having One ChiralityCenter Are Chiral
A chirality center is a tetrahedral carbon atom that is bonded to four different groups
A molecule that contains one chirality center is chiral and can exist as a pair of enantiomers
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The presence of a single chirality center in a molecule guarantees that the molecule is chiral and that enantiomeric forms are possible
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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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)
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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Me Et
ClH
(III)
CH
EtMeCl*
Me Et
HCl
mirror
MeEt
Cl H
(IV)
(III) and (IV) are nonsuperimposable mirror images of each other
Me Et
ClH
(III)
sameas
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Me Me
ClH
(V)
CH
MeMeCl
Me Me
HCl
mirror
MeMe
Cl H
(VI)Me Me
ClH
(V)
sameas
(V) and (VI) are superimposable⇒ not enantiomers ⇒ achiral
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4A.Tetrahedral vs. TrigonalStereogenic Centers
Chirality centers are tetrahedral stereogenic centers
Me Et
OHH
*(A)
mirror
MeEt
HO 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
Cis and trans alkene isomers contain trigonal stereogenic centers
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5. More about the BiologicalImportance of Chirality
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The activity of drugs containing chirality centers can vary between enantiomers, sometimes with serious or even tragic consequences
For several years before 1963 thalidomide was used to alleviate the symptoms of morning sickness in pregnant women
Thalidomide
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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
O
enantiomer ofThalidomide
(causes birth defects)(cures morning sickness)
© 2014 by John Wiley & Sons, Inc. All rights reserved.
6. How to Test for Chirality:Planes of Symmetry
A molecule will not be chiral if it possesses a plane of symmetry
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
All molecules with a plane of symmetry in their most symmetric conformation are achiral
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Me Me
Cl
H
Me Et
Cl
H
Plane of symmetry
No plane of symmetry
achiral
chiral
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7. Naming Enantiomers:The R,S -System
Using only the IUPAC naming that we have learned so far, these two enantiomers will have the same name:● 2-Butanol
This is undesirable because each compound must have its own distinct name
OHH
(I)
HO H
(II)
OHRecall:
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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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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.
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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 H
Step 2: CH3
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-Butanol
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OCH3
H3C CH2CH3Br
Other examples
①
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
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
Other examples
①④
②
③
OCH3
IH3C
● Rotate C–CH3 bond such that H is pointed to the back
Counter-clockwise
(S)
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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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Example CH3
H CH=CH2HO①
④ ②
③
(S)
CH3 CH CH2
CH
CCC
HH
CH3
CH CH2
Compare & :
equivalent to
Thus, (H, H, H)
(C, C, H)CH CH2
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Other examples
OH
HCl
CH3
O①
④
②
③
(R)
H2C
HCl
CH3
O
OH
①
④②
③
(S)
C (O, O, C)
C (O, H, H)
②
③
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8. Properties of Enantiomers:Optical Activity
Enantiomers●Mirror images that are not
superimposable
mirror
H3CH2C
*
CH3
H
ClCH2CH3
*
H3C
H
Cl
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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
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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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Optical activity●The property possessed by
chiral substances of rotating the plane of polarization of plane-polarized light
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The electric field (like the magnetic field) of light is oscillating in all possible planes
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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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[] =
25 c 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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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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Two enantiomers should have the same value of specific rotation, but the signs are opposite
mirror
HO
*
CH2CH3
CH3
H
[] = + 13.5o25
D
OH
*
H3CH2C
CH3
H
[] = 13.5o25
D
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9. The Origin of Optical Activity
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9. The Origin of Optical Activity
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9. The Origin of Optical Activity
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An equimolar mixture of two enantiomers is called a racemic mixture (or racemate or racemic form)
A racemic mixture causes no net rotation of plane-polarized light
9A.Racemic Forms
HC2H5
CH3
OH
(R)-2-Butanol
HC2H5
H3C
HO
(S)-2-Butanol(if present)
rotation
equal & opposite rotation by the enantiomer
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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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An enantiomerically pure sample of (S)-(+)-2-butanol shows a specific rotation of +13.52
D[] = +13.52
25
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
Such a sample is said to have an enantiomeric excess less than 100%
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Enantiomeric excess (ee) ●Also known as the optical
purity% enantiomeric
excess
moles of oneenantiomer
moles of otherenantiomer
total moles of both enantiomers
= x 100
% enantiomericexcess *
observed specific rotation
specific rotation of thepure enantiomers
= x 100
●Can be calculated from optical rotations
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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%
© 2014 by John Wiley & Sons, Inc. All rights reserved.
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))
© 2014 by John Wiley & Sons, Inc. All rights reserved.
© 2014 by John Wiley & Sons, Inc. All rights reserved.
10B. Stereoselective Syntheses 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
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OEt
O
FOH
O
F
+ EtOHH+, H2O
heat
racemate ( ) racemate ( )
OEt
O
FOH
O
F
+ EtOH
H2Olipase
racemate ( ) ( )(> 69% ee)
OEt
O
F(+)
(> 99% ee)
+
© 2014 by John Wiley & Sons, Inc. All rights reserved.
11.Chiral Drugs
Of the $475 billion in world-wide sales of formulated pharmaceutical products in 2008, $205 billion was attributable to single enantiomer drugs
ONMe2
F
NC
Escitalpram(anti-depressant )
HO
HO
NH3
HCO2
L-DOPA(treatment for Parkinson's)
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Singulair(asthma and allergy treatment)
Naproxen(anti-inflammatory drug)
MeO
CH3
CO2H
N
HOCH3
CH3S
NaO2C
Cl
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12.Molecules with More than OneChirality Center
In compounds with n tetrahedral stereocenters, the maximum number of stereoisomers is 2n
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12A. How to Draw Stereoisomers forMolecules Having More than OneChirality Center
Br
Br
2,3-Dibromopentane** 12
35
4
© 2014 by John Wiley & Sons, Inc. All rights reserved.
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
C2C3
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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
Br BrH H
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To draw the enantiomer of the first stereoisomer, we simply draw its mirror image
Br BrH H
BrBrHH
mirror
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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
Br HH Br
BrHHBr
mirror
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Next we examine the relationship between all of the possible pairings of formulas to determine which are pairs of enantiomers, which are diastereomers
Br BrH H
BrBrHH
Br HH Br
BrHHBr
1 2 3 4
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Structures 1 and 2 are enantiomers; structures 3 and 4 are also enantiomers
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
Br BrH H
BrBrHH
Br HH Br
BrHHBr
1 2 3 4
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Diastereomers●Stereoisomers that are not
enantiomers
●Unlike enantiomers, diastereomers usually have substantially different chemical and physical properties
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C H
C HCH3
Cl
Br
HOCH
CHCH3
Cl
Br
OH(I) (II )
C H
C HHO
Cl
Br
CH3
CH
CHOH
Cl
Br
CH3(III ) (IV)
(I) & (II) are enantiomers of each other
(III) & (IV) are enantiomers of each other
© 2014 by John Wiley & Sons, Inc. All rights reserved.
C H
C HCH3
Cl
Br
HOCH
CHCH3
Cl
Br
OH(I) (II )
C H
C HHO
Cl
Br
CH3
CH
CHOH
Cl
Br
CH3(III ) (IV)
Diastereomers of each other:●(I) & (III), (I) & (IV), (II) & (III),
(II) & (IV)
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12B. Meso Compounds
Compounds with two stereocenters do not always have four stereoisomers (22 = 4) since some molecules are achiral (not chiral), even though they contain stereocenters
For example, 2,3-dichlorobutane has two stereocenters, but only has 3 stereoisomers (not 4)
© 2014 by John Wiley & Sons, Inc. All rights reserved.
C Br
C BrH
CH3
H
CH3
CBr
CBrH
CH3
H
CH3(I) (II )
C Br
C BrCH3
CH3
H
HCBr
CBrCH3
CH3
H
H(III ) (IV)
Note: (III) contains a plane of symmetry, is a meso compound, and is achiral([a] = 0o).
© 2014 by John Wiley & Sons, Inc. All rights reserved.
C Br
C BrH
CH3
H
CH3
CBr
CBrH
CH3
H
CH3(I) (II )
C Br
C BrCH3
CH3
H
HCBr
CBrCH3
CH3
H
H(III ) (IV)
(I) & (II) are enantiomers of each other and chiral
(III) & (IV) are identical and achiral
© 2014 by John Wiley & Sons, Inc. All rights reserved.
C Br
C BrH
CH3
H
CH3
CBr
CBrH
CH3
H
CH3(I) (II )
C Br
C BrCH3
CH3
H
HCBr
CBrCH3
CH3
H
H(III ) (IV)
(I) & (III), (II) & (III) are diastereomers
Only 3 stereoisomers:●(I) & (II) {enantiomers}, (III) =
(IV) {meso}
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12C. How to Name Compounds withMore than One Chirality Center
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
© 2014 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
HaHbBr
CH3
Br1
23 4
①④
②③
C3: (R) configuration
●Full name: (2R, 3R)-2,3-Dibromobutane
© 2014 by John Wiley & Sons, Inc. All rights reserved.
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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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
mirror
enantiomers
(I) and (II) are both chiral and they are enantiomers of each other
© 2014 by John Wiley & Sons, Inc. All rights reserved.
H3C
Cl
CH3
ClH H
(III)(2S, 3R)-Dichlorobutane
H Cl
H Cl
CH3
CH3
(III) is achiral (a meso compound) (III) and (I) are diastereomers of
each other
Plane ofsymmetry
© 2014 by John Wiley & Sons, Inc. All rights reserved.
14.Stereoisomerism of CyclicCompounds
Me
H Me
H Me
H Me
H
mirror
enantiomers
H
Me Me
H
Plane ofsymmetry
a meso compoundachiral
© 2014 by John Wiley & Sons, Inc. All rights reserved.
14A. Cyclohexane Derivatives
Me
Me
Me
Me
1,4-Dimethylcyclohexane
Plane ofsymmetry
H
Me
Me
H
H
Me
H
Me
cis-1,4-dimethylcyclohexane
trans-1,4-dimethylcyclohexane
• Both cis- & trans-1,4-dimethylcyclo-hexanes are achiral and optically inactive
• The cis & trans forms are diastereomers
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Me Me**
cis-1,3-dimethylcyclohexane
1,3-DimethylcyclohexanePlane of
symmetry
(meso)
H
Me
H
Me
●cis-1,3-Dimethylcyclohexane has a plane of symmetry and is a meso compound
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Me Me**
trans-1,3-dimethylcyclohexane
1,3-Dimethylcyclohexane
NO plane of symmetry
enantiomers
H
Me
Me
HH
Me
Me
H
●trans-1,3-Dimethylcyclohexane exists as a pair of enantiomers
© 2014 by John Wiley & Sons, Inc. All rights reserved.
1,3-Dimethylcyclohexane●Has two chirality centers but
only three stereoisomers
(meso)
H
Me
H
Me
cis-1,3-dimethylcyclohexane
enantiomers
H
Me
Me
HH
Me
Me
H
trans-1,3-dimethylcyclohexane
© 2014 by John Wiley & Sons, Inc. All rights reserved.
1,2-Dimethylcyclohexane
enantiomers
H
H
MeMe
H
H
MeMe
●trans-1,2-Dimethylcyclohexane exists as a pair of enantiomers
mirror
© 2014 by John Wiley & Sons, Inc. All rights reserved.
1,2-Dimethylcyclohexane●With cis-1,2-
dimethylcyclohexane the situation is quite complicated
Me
H
MeH
Me
H
MeH
(I) (II)
●(I) and (II) are enantiomers to each other
mirror
© 2014 by John Wiley & Sons, Inc. All rights reserved.
●However, (II) can rapidly be interconverted to (III) by a ring flip Me
H
MeH
12
Me
H
MeH
(I) (II)
1'
2'mirror
H
Me 12
Me
H(III)
© 2014 by John Wiley & Sons, Inc. All rights reserved.
●Rotation of (III) along the vertical axis gives (I)
Me
H
MeH
12
H
Me12
Me
H
Me
H
MeH
(I) (II)
(III)
1'
2'
C1 of (II) and (III) become C2’ of (I) & C2 of (II) and (III) become C1’ of (I)
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Me
H
MeH
12
H
Me12
Me
H
Me
H
MeH
(I) (II)
(III)
1'
2'
Although (I) and (II) are enantiomers to each other, they can interconvert rapidly (I) and (II) are achiral
© 2014 by John Wiley & Sons, Inc. All rights reserved.
15.Relating Configurations throughReactions in Which No Bonds tothe Chirality Center Are Broken
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
© 2014 by John Wiley & Sons, Inc. All rights reserved.
H
O
Me H
HOH
Me HH
NaBH4
MeOH
Ph Br
NaCN
DMSO
Me H
Ph CN
Me H
Same configuration
Same configuration
© 2014 by John Wiley & Sons, Inc. All rights reserved.
15A. Relative & Absolute Configurations 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 Y
AB
CX
AB
C
The chirality centersin I and II have thesame relativeconfiguration. Theircommon groups andcentral carbon canbe superimposed.
I
II
© 2014 by John Wiley & Sons, Inc. All rights reserved.
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
enantiomers
© 2014 by John Wiley & Sons, Inc. All rights reserved.
16.Separation of Enantiomers:Resolution
e.g.R R'
OH
*(racemic)
ClOMe
O
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.
Resolution – separation of two enantiomers
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Kinetic Resolution
R2
R1R
OH
*R2
R1R
OH
*R2
R1R
OH
*O
+
(racemic)
●One enantiomer reacts “fast” and another enantiomer reacts “slow”
© 2014 by John Wiley & Sons, Inc. All rights reserved.
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
* stop reaction at 50%* maximum yield = 50%
(-)-DET:COOEt
COOEtHO
HO
(D)-(-)-Diethyl Tartrate
© 2014 by John Wiley & Sons, Inc. All rights reserved.
17.Compounds with ChiralityCenters Other than Carbon
R1
SiR2
R4 R3
R1
GeR2
H R3
R1
NR2
R4 R3
X SR2 R1
O
© 2014 by John Wiley & Sons, Inc. All rights reserved.
18.Chiral Molecules That Do NotPossess a Chirality Center
P(Ph)2
P(Ph)2
(Ph)2P
(Ph)2P
(S)-BINAP (R)-BINAP
enantiomers
© 2014 by John Wiley & Sons, Inc. All rights reserved.
enantiomers
C C
Cl
H
CCl
HCC
Cl
H
CCl
H
mirror
© 2014 by John Wiley & Sons, Inc. All rights reserved.
END OF CHAPTER 5