Chapter 5: Stereochemistry Chapter 5, continuedâ¦
Chapter 5: Stereochemistry • Stereoisomers – Cis/trans isomers – Enantiomers • Drawing enantiomers • R,S nomenclature • Optical activity
– More than one asymmetric carbon • Meso compounds • R,S nomenclature
• Reactions
Chapter 5, continued… • Reactions w/ asymmetric carbons – Relative vs. absolute configurations – Separation of enantiomers – Enantiomers in biological systems – More terminology – Asymmetric atoms that aren’t Carbon – Stereochemistry of electrophilic addition reactions of alkenes
Isomers Nonidentical compounds having the same molecular formula
1
Cis-Trans Isomers
Enantiomers nonsuperimposable mirror-image molecules
Achiral compounds have superimposable mirror images Chiral compounds have nonsuperimposable mirror images
2
A stereocenter (stereogenic center) is an atom at which the interchange of two groups produces a stereoisomer
Important terms: • • • • •
Chiral Chirality center Asymmetric carbon Enantiomer Stereocenter
Naming Enantiomers The R,S system of nomenclature Rank the groups (atoms) bonded to the chirality center
3
Orient the lowest priority (4) away from you Then draw an arrow from 1 to 2
Clockwise = R configuration Counterclockwise = S configuration
Naming from the Perspective Formula 1. Rank the groups bonded to the asymmetric carbon 1 4 2
3
2. If the group (or atom) with the lowest priority is bonded by hatched wedge,
3. If necessary, switch two groups so that the lowest priority group (or atom) is bonded by a hatched wedge. Note that when you do this, you obtain the opposite configuration!
4. You can draw group 1 to group 2, passing group 4, but never 3
4
Naming from the Fischer Projection 1. Rank the groups (or atom) that are bonded to the asymmetric carbon and draw an arrow from the highest priority to the next highest priority Cl CH2CH2CH3
CH3CH2
(R)-3-chlorohexane
H
2. If the lowest priority is on a horizontal bond, the naming is opposite to the direction of the arrow CH3 H
OH
(S)-2-butanol
CH2CH3
3. The arrow can go from group 1 to 2, passing group 4, but not group 3
CO2H CH3
H OH
(S)-lactic acid
A Fischer projection can only be rotated 180° in the plane of the paper to yield the same molecule
Optical Activity Chiral compounds are optically active; they rotate the plane of polarized light.
Clockwise (+)
Counterclockwise (-)
Different from R,S configuration
Achiral compounds do not rotate the plane of polarized light. They are optically inactive.
5
A polarizer measures the degree of optical rotation of a compound The observed rotation (α)
[α ]Τλ = α
lxc
[α ]Tλ = specific rotation T is the temp in °C λ is the wavelength
α is the measured rotation in degrees l is the path length in decimeters c is the concentration in grams per mL Each optically active compound has a characteristic specific rotation
A racemic mixture, which contains an equal amount of the two enantiomers, is optically inactive observed specific rotation optical purity = specific rotation of the pure enantiomer
enantiomeric excess =
excess of a single enantiomer entire mixture
If a mixture has an e.e. of 60%, what is the percentage of each isomer in the mixture?
More than one asymmetric carbon: a maximum of 2n stereoisomers can be obtained * * CH3CHCHCH3 Cl OH
6
Diastereomers: stereoisomers that are not enantiomers Which compounds from the previous slide are diastereomers? Diastereomers: different physical and chemical properties
Erythro vs. Threo enantiomers: To determine, draw eclipsed conformations or Fischer projections. Erythro has similar groups on the same side
Identification of Asymmetric Carbons in Cyclic Compounds H
these two groups * are different
H
Br
* CH3
H
H H
H
CH3
CH3
Br
Br
cis-1-bromo-3-methylcyclohexane
H
H CH3
CH3
H
H
Br
Br
trans-1-bromo-3-methylcyclohexane
7
Meso Compounds Have two or more asymmetric carbons and a plane of symmetry and are thus achiral
As long as any one conformer of a compound has a plane of symmetry, the compound will be achiral
plane of symmetry no plane of symmetry
8
The R,S nomenclature of isomers with more than one asymmetric carbon
Reactions of compounds that contain an asymmetric carbon. CH2CH2CH2OH
CH2CH2CH2Cl H CH3CH2
H
-
OH
CH3CH2
CH3
CH
CH2
H CH3
CH3
CH2CH3
H2
H CH3 No reaction at the asymmetric carbon; both the reagent and the product have the same relative configuration (although the absolute configuration may change—ex. 2). CH3CH2CH2
Pd/C
CH3CH2CH2
If a reaction breaks a bond at the asymmetric carbon, you need to know the reaction mechanism in order to predict the relative configuration of the product.
Resolution of a Racemic Mixture (R)-acid (S)-acid enantiomers
(S)-base
(R,S)-salt (S,S)-salt diastereomers
(R,S)-salt (S,S)-salt HCl
HCl
(S)-baseH+ (S)-baseH+ + + (S)-acid (R)-acid
9
Discrimination of Enantiomers by Biological Molecules
Terminology Associated with Stereochemistry prochiral carbon
pro-R-hydrogen
pro-S-hydrogen
Enantiotopic hydrogens have the same chemical reactivity and cannot be distinguished by achiral agents, but they are not chemically equivalent toward chiral reagents
Diastereotopic hydrogens do not have the same reactivity with achiral reagents
10
A regioselective reaction: preferential formation of one constitutional isomer
A stereoselective reaction: preferential formation of a stereoisomer
A stereospecific reaction: each stereoisomeric reactant produces a different stereoisomeric product or a different set of products
All stereospecific reactions are stereoselective Not all stereoselective reactions are stereospecific
Atoms other than carbon can be asymmetric CH3 BrCH3CH2CH2
N+
H CH2CH3
P
BrH N+ CH2CH2CH3 CH3CH2
O
O CH3CH2O
CH3
H OCH3
H P OCH2CH3 CH3O
11
Amine Inversion If one of the groups attached to N is a lone pair, then the enantiomers cannot be separated.
Stereochemistry of Electrophilic Addition Reactions of Alkenes
What is the absolute configuration of the product?
Addition reactions that form one asymmetric carbon
Is this reaction stereoselective? Stereospecific?
12
CH3 CH3CH2C
CH3 CH2
+
HBr
peroxide
CH3CH2CHCH2Br * 1-bromo-2-methylbutane
2-methyl-1-butene
Is this reaction stereoselective? Stereospecific?
Addition reactions that form an additional asymmetric carbon
Addition reactions that form two asymmetric carbons A carbocation reaction intermediate CH3CH2 C
CH2CH3 CH3CH2CH
CH3
H3C CH3CH2 H3C
Cl + HCl
C
CH3
C
C
C
C
Cl
H CH2CH3
CH2CH3
H3C
H CH3CH2 Cl
CH3
CCH2CH3
CH3 CH3 CH3CH2 Cl C H3C
CH3 C
H CH2CH3
CH2CH3
H3C C
H CH3CH2
C
Cl CH3
Two substituents added to the same side of the double bond: syn Two substituents added to opposite sides of the double bond: anti
13
Addition reactions that form two asymmetric carbons A radical reaction intermediate
Stereochemistry of Hydrogen Addition (Syn Addition)
Hydrogenation of Cyclic Alkenes H +
H3C
H2
Pt/C
H
CH3 CH(CH3)2
CH(CH3)2 H3C H
CH(CH3)2 H
Only cis isomers are obtained with alkenes containing fewer than eight ring atoms Both cis and trans isomers are possible for rings containing eight or more ring atoms
14
Stereochemistry of Hydroboration– Oxidation
Syn addition of borane
Syn addition of H2O
Addition reactions that form a bromonium ion intermediate (anti addition)
15
– More than one asymmetric carbon • Meso compounds • R,S nomenclature
• Reactions
Chapter 5, continued… • Reactions w/ asymmetric carbons – Relative vs. absolute configurations – Separation of enantiomers – Enantiomers in biological systems – More terminology – Asymmetric atoms that aren’t Carbon – Stereochemistry of electrophilic addition reactions of alkenes
Isomers Nonidentical compounds having the same molecular formula
1
Cis-Trans Isomers
Enantiomers nonsuperimposable mirror-image molecules
Achiral compounds have superimposable mirror images Chiral compounds have nonsuperimposable mirror images
2
A stereocenter (stereogenic center) is an atom at which the interchange of two groups produces a stereoisomer
Important terms: • • • • •
Chiral Chirality center Asymmetric carbon Enantiomer Stereocenter
Naming Enantiomers The R,S system of nomenclature Rank the groups (atoms) bonded to the chirality center
3
Orient the lowest priority (4) away from you Then draw an arrow from 1 to 2
Clockwise = R configuration Counterclockwise = S configuration
Naming from the Perspective Formula 1. Rank the groups bonded to the asymmetric carbon 1 4 2
3
2. If the group (or atom) with the lowest priority is bonded by hatched wedge,
3. If necessary, switch two groups so that the lowest priority group (or atom) is bonded by a hatched wedge. Note that when you do this, you obtain the opposite configuration!
4. You can draw group 1 to group 2, passing group 4, but never 3
4
Naming from the Fischer Projection 1. Rank the groups (or atom) that are bonded to the asymmetric carbon and draw an arrow from the highest priority to the next highest priority Cl CH2CH2CH3
CH3CH2
(R)-3-chlorohexane
H
2. If the lowest priority is on a horizontal bond, the naming is opposite to the direction of the arrow CH3 H
OH
(S)-2-butanol
CH2CH3
3. The arrow can go from group 1 to 2, passing group 4, but not group 3
CO2H CH3
H OH
(S)-lactic acid
A Fischer projection can only be rotated 180° in the plane of the paper to yield the same molecule
Optical Activity Chiral compounds are optically active; they rotate the plane of polarized light.
Clockwise (+)
Counterclockwise (-)
Different from R,S configuration
Achiral compounds do not rotate the plane of polarized light. They are optically inactive.
5
A polarizer measures the degree of optical rotation of a compound The observed rotation (α)
[α ]Τλ = α
lxc
[α ]Tλ = specific rotation T is the temp in °C λ is the wavelength
α is the measured rotation in degrees l is the path length in decimeters c is the concentration in grams per mL Each optically active compound has a characteristic specific rotation
A racemic mixture, which contains an equal amount of the two enantiomers, is optically inactive observed specific rotation optical purity = specific rotation of the pure enantiomer
enantiomeric excess =
excess of a single enantiomer entire mixture
If a mixture has an e.e. of 60%, what is the percentage of each isomer in the mixture?
More than one asymmetric carbon: a maximum of 2n stereoisomers can be obtained * * CH3CHCHCH3 Cl OH
6
Diastereomers: stereoisomers that are not enantiomers Which compounds from the previous slide are diastereomers? Diastereomers: different physical and chemical properties
Erythro vs. Threo enantiomers: To determine, draw eclipsed conformations or Fischer projections. Erythro has similar groups on the same side
Identification of Asymmetric Carbons in Cyclic Compounds H
these two groups * are different
H
Br
* CH3
H
H H
H
CH3
CH3
Br
Br
cis-1-bromo-3-methylcyclohexane
H
H CH3
CH3
H
H
Br
Br
trans-1-bromo-3-methylcyclohexane
7
Meso Compounds Have two or more asymmetric carbons and a plane of symmetry and are thus achiral
As long as any one conformer of a compound has a plane of symmetry, the compound will be achiral
plane of symmetry no plane of symmetry
8
The R,S nomenclature of isomers with more than one asymmetric carbon
Reactions of compounds that contain an asymmetric carbon. CH2CH2CH2OH
CH2CH2CH2Cl H CH3CH2
H
-
OH
CH3CH2
CH3
CH
CH2
H CH3
CH3
CH2CH3
H2
H CH3 No reaction at the asymmetric carbon; both the reagent and the product have the same relative configuration (although the absolute configuration may change—ex. 2). CH3CH2CH2
Pd/C
CH3CH2CH2
If a reaction breaks a bond at the asymmetric carbon, you need to know the reaction mechanism in order to predict the relative configuration of the product.
Resolution of a Racemic Mixture (R)-acid (S)-acid enantiomers
(S)-base
(R,S)-salt (S,S)-salt diastereomers
(R,S)-salt (S,S)-salt HCl
HCl
(S)-baseH+ (S)-baseH+ + + (S)-acid (R)-acid
9
Discrimination of Enantiomers by Biological Molecules
Terminology Associated with Stereochemistry prochiral carbon
pro-R-hydrogen
pro-S-hydrogen
Enantiotopic hydrogens have the same chemical reactivity and cannot be distinguished by achiral agents, but they are not chemically equivalent toward chiral reagents
Diastereotopic hydrogens do not have the same reactivity with achiral reagents
10
A regioselective reaction: preferential formation of one constitutional isomer
A stereoselective reaction: preferential formation of a stereoisomer
A stereospecific reaction: each stereoisomeric reactant produces a different stereoisomeric product or a different set of products
All stereospecific reactions are stereoselective Not all stereoselective reactions are stereospecific
Atoms other than carbon can be asymmetric CH3 BrCH3CH2CH2
N+
H CH2CH3
P
BrH N+ CH2CH2CH3 CH3CH2
O
O CH3CH2O
CH3
H OCH3
H P OCH2CH3 CH3O
11
Amine Inversion If one of the groups attached to N is a lone pair, then the enantiomers cannot be separated.
Stereochemistry of Electrophilic Addition Reactions of Alkenes
What is the absolute configuration of the product?
Addition reactions that form one asymmetric carbon
Is this reaction stereoselective? Stereospecific?
12
CH3 CH3CH2C
CH3 CH2
+
HBr
peroxide
CH3CH2CHCH2Br * 1-bromo-2-methylbutane
2-methyl-1-butene
Is this reaction stereoselective? Stereospecific?
Addition reactions that form an additional asymmetric carbon
Addition reactions that form two asymmetric carbons A carbocation reaction intermediate CH3CH2 C
CH2CH3 CH3CH2CH
CH3
H3C CH3CH2 H3C
Cl + HCl
C
CH3
C
C
C
C
Cl
H CH2CH3
CH2CH3
H3C
H CH3CH2 Cl
CH3
CCH2CH3
CH3 CH3 CH3CH2 Cl C H3C
CH3 C
H CH2CH3
CH2CH3
H3C C
H CH3CH2
C
Cl CH3
Two substituents added to the same side of the double bond: syn Two substituents added to opposite sides of the double bond: anti
13
Addition reactions that form two asymmetric carbons A radical reaction intermediate
Stereochemistry of Hydrogen Addition (Syn Addition)
Hydrogenation of Cyclic Alkenes H +
H3C
H2
Pt/C
H
CH3 CH(CH3)2
CH(CH3)2 H3C H
CH(CH3)2 H
Only cis isomers are obtained with alkenes containing fewer than eight ring atoms Both cis and trans isomers are possible for rings containing eight or more ring atoms
14
Stereochemistry of Hydroboration– Oxidation
Syn addition of borane
Syn addition of H2O
Addition reactions that form a bromonium ion intermediate (anti addition)
15
