8 stereochemistry - elsevier 8 sterochemistry slides...cyclobutane with two equivalent chiral...
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8.2 MIRROR IMAGE OBJECTS, MIRROR IMAGE MOLECULES AND CHIRALITYFigure 8.1 Objects and Their Mirror ImagesIn (a), the chair and its mirror image are identical. !ey can be superimposed. In (b), the mirror image, side-arm chairs cannot be superimposed. One chair has a “right-handed” arm, the other has a “left-handed” arm. (!ese particular chairs were designed by the renowned woodworker George Nakashima.)
8.2 MIRROR IMAGE OBJECTS, MIRROR IMAGE MOLECULES AND CHIRALITY
Figure 8.2 Nonsuperimosable Mirror ImagesA left and a right hand are nonsuperimposable mirror images. (M. C. Escher, Drawing Hands)
C CH H
Cl Cl
F FBrBr
mirror
HH
ClCl
BrFF
mirror
Br
(b)
(a)
Figure 8.3 Nonsuperimosable Mirror Image MoleculesBromochloro!uoromethane does not have a plane of symmetry. "erefore, it is chiral, and it exists as a pair of nonsuperimposable mirror image isomers. (a) Schematic diagram; (b) Ball-and-stick molecular models.
8.2 MIRROR IMAGE OBJECTS, MIRROR IMAGE MOLECULES AND CHIRALITY
HH
ClH
ClCl
planes of symmetry
Figure 8.4 Planes of Symmetry in DichloromethaneDichloromethane, which has not one, but two planes of symmetry can be superimposed on its mirror image. It is achiral.
8.2 MIRROR IMAGE OBJECTS, MIRROR IMAGE MOLECULES AND CHIRALITY
plane of symmetry
Cl
Br
HH
Figure 8.4 Planes of Symmetry in DichloromethaneDichloromethane, which has not one, but two planes of symmetry can be superimposed on its mirror image. It is achiral.
8.2 MIRROR IMAGE OBJECTS, MIRROR IMAGE MOLECULES AND CHIRALITY
8.2 MIRROR IMAGE OBJECTS, MIRROR IMAGE MOLECULES AND CHIRALITY
Figure 8.5 Plane of Symmetry in BromochloromethaneBromochloromethane has a plane of symmetry, and therefore it can be superimposed on its mirror image. It is achiral.
plane of symmetry
Cl
Br
HH
8.2 MIRROR IMAGE OBJECTS, MIRROR IMAGE MOLECULES AND CHIRALITYMirror Image Isomers
C CH3
Br
H 2-bromobutane(a chiral molecule)
stereogenic center
CH3 C CH3
Br
H 2-bromopropane(an achiral molecule)
not a stereogenic center
CH3CH2
CH2 C
Br
H
butyl group pentyl group
butyl group butenyl group
CH2CH2CH3
CH2 C
Br
H
CH2CH2CH3 CH2 CH CH2CH2
CH3CH2CH2CH2CH2
5-bromodecane
5-bromo-1-nonene
Figure 8.6 Schematic Diagram of a PolarimeterPlane-polarized light is obtained by passing light through a polarizing !lter. Any chiral compound in the sample tube rotates the plane-polarized light. "e direction and magnitude of the rotation are determined by rotating the analyzer to allow the light to pass through with maximum brightness. In a modern instrument this is all done electronically, but the basic principle is the same.
Sodium lamp
Polarizer
Plane ofpolarized light
Sample tube
Rotated planeof polarized light
Analyzer rotated to passlight with scale to read angle
8.3 OPTICAL ACTIVITYPlane Polarized Light
Table 8.1 Specific Rotations of Common CompoundsCompound [!]D
azidothymidine (AZT) +99!cefotaxin (a cephalosporin) +55!cholesterol "31.5!cocaine "16!codeine "136!epinephrine (adrenaline) "5.0!levodopa "13.1!monosodium glutamate (MSG) +25.5!morphine "132!oxacillin (a penicillin) +201!progesterone +172!sucrose +66!testosterone +109!
8.3 OPTICAL ACTIVITYSpecific Rotation
[!]D = !obs
l x c
Figure 8.6 Schematic Diagrams of Plane and Circularly Polarized Light(a) In plane polarized light, the electric !eld vectors of the light all oscillate in a single plane. (b) In circularly polarized light, the electric !eld vec-tor can rotate in a right-handed (clockwise) or left-handed (counterclockwise) direction. (c) If right-handed and left-handed phases of circularly polarized light are superimposed, the electric !eld vectors in the +x- "x directions cancel, and the y-components are additive, and directed along the y-axis. #e net result is plane-polarized light.
Mirror image helices
(b)
Plane polarized light (side view)
E
B
x
(a)
(c)
right-handed phase
left-handed phase
x
y
8.3 OPTICAL ACTIVITYCircularly Polarized Light and Optical Rotation
8.3 OPTICAL ACTIVITYOptical Purity
optical purity =observed rotation
rotation of pure enantiomerx 100%
Figure 8.7 Fischer Projection Structures of Glyceraldehyde(a) Perspective structures of glyceraldehyde. (b) Projection structures. (c) Fisher projection structures of the enantiomers glyceraldehyde. !e chiral center is located at the point where the bond lines intersect. !e carbon atom is not usually shown. !e vertical lines extend away from the viewer, behind the plane of the page; horizontal lines extend toward the viewer, out of the plane of the page, as shown in part (b).
Mirror
Perspective Structures
C
CHO
OHH
HOCH2
A
C
CHO
CH2OHH
HO
B
CHO
C OHH
CHO
C
CH2OH
HHO
A B
Fischer projection structures
H OH
CHO
CH2OH
HO H
CHO
CH2OH
A B
CH2OH
(a)
(b)
(c)
8.4 FISCHER PROJECTION FORMULAS
Figure 8.8 Kahn-Ingold-Prelog System of Configurational NomenclaturePlace the lowest priority atom or group away from your eye, and view the chiral site along the axis of the carbon-bond to the lowest priority group. (!e diagram of the eye in this "gure is from a drawing in the notebooks of Leonardo da Vinci.)
C
1
423 C
1
234
lowest priority atom Clockwise rotation from 1, to 2,to 3 gives R configuration.
8.5 ABSOLUTE CONFIGURATIONR,S Configurations: The Kahn-Ingold-Prelog System of Configurational Nomenclatur
Figure 8.10 Enantiomers and DiastereomersA molecule that contains two nonequivalent chiral centers, such as 2,3-4-trihydroxybutanal, can exist as four stereoisomers. !ey exist as two pairs of enantiomers. Stereoisomers that are not enantiomers are diastereomers.
Enantiomers
H OH
CHO
OHH
CH2OH
HO H
CHO
HHO
CH2OH
H OH
CHO
HHO
CH2OH
HO H
CHO
OHH
CH2OHI II III IV
[!]D -21.5 +21.5 -29.1 +29.1
Enantiomers
8.6 MOLECULES WITH TWO !OR MORE" STEREOGENIC CENTERSNonequivalent Stereogenic Centers
Figure 8.11 Configurations of Enantiomers and Diastereomers
CHO
CH OH
OH
CH
CHO
CH OH
H
COHHOCH2 HOCH2
Diastereomers
I (2R,3R)[!]D = -21.5o
III (2R,3S)[!]D =-29.1o
CHO
CHO H
H
COH
CHO
CH OH
OH
CHHOCH2 HOCH2
Diastereomers
II (2S,3S)[!]D = + 21.5o
IV (2S,3R)[!]D = +29.1o
Enantiomers Enantiomers
8.6 MOLECULES WITH TWO !OR MORE" STEREOGENIC CENTERSNonequivalent Stereogenic Centers
Figure 8.12 Configurations of Optically Active Tartaric Acids and Meso CompoundsOnly three stereoisomers exist for tartaric acid because it has two equivalent chiral centers. Two of the stereoisomers are enantiomers. !e third has a plane of symmetry, is optically inactive, and is called a meso compound; i.e. meso-tartaric acid.
C
COHH
CO2H
CO2H
OHHC
COHH
CO2H
CO2H
HHO
(2S,3S)
1 11
1
C
CHHO
CO2H
CO2H
HHOC
CHHO
CO2H
CO2H
HHO
(2R,3S)(2R,3S)
Enantiomers Same compound
(2S,3R)
C
CHHO
CO2H
CO2H
HHO
(2R,3S)
rotate 180o
C
CHHO
CO2H
CO2H
HHO
(2S,3R)
2 2 2 2
1
1
2 2
4
3
4
3
3 3 3 3
4 4 4 4
8.6 MOLECULES WITH TWO !OR MORE" STEREOGENIC CENTERSNonequivalent Stereogenic Centers
methylcyclohexane
CH3H
methylcyclohexane
CH3
plane of symmetry
(R)-4-methylcyclohexene
CH3H
8.7 Cyclic Molecules with Stereogenic CentersCyclic Structures with One Stereogenic Center
Br
H
H
Cl
R S
R
Br
H
H
ClS
(b) Diastereomers of 1,2-dibromocyclobutane
Br
H
Br
H
R
S
Meso compound
Mirror
Br
H
H
Cl
R S
R
Br
H
H
ClS
Br
H
Cl
H
R
R
S
Br
H
Cl
HS
(a) Diastereomers of 1-bromo-2-chlorocyclobutane
8.7 Cyclic Molecules with Stereogenic CentersCyclic Structures with Two Stereogenic Centers: Disubstituted Cyclobutanes
Figure 8.13 Diastereomers of 1,2-Disubstituted Cyclobutanes(a) A 1,2-disubstituted cyclobutane with two nonequivalent chiral centers has four diastereomers. (b) However, a 1,2-disubstituted cyclobutane with two equivalent chiral centers has only three diastereomers, one of which is a meso compound.
Figure 8.14 Stereoisomers of 1,4-Dimethylcyclohexane!e cis and trans isomers of 1,4-dimethylcyclohexane are achiral because each has a plane of symmetry.
cis-1,4-dimethylcyclohexane
H3C
CH3
CH3
CH3
Symmetry plane
H3C CH3
CH3
CH3
Symmetry plane
trans-1,4-dimethylcyclohexane
8.7 Cyclic Molecules with Stereogenic CentersCyclic Structures with Two Stereogenic Centers: Dimethyl Cyclohexanes
Mirror
CH3
H3C
H3C
CH3
same asmeso-cis-1,3-dimethylcyclohexane
CH3
H3C
CH3
CH3
Symmetry plane Symmetry plane
Mirror
H3C CH3
enantiomerstrans-1,3-dimethylcyclohexane
CH3
H3C
CH3
CH3
CH3 CH3
8.7 Cyclic Molecules with Stereogenic CentersCyclic Structures with Two Stereogenic Centers: Dimethyl Cyclohexanes
Figure 8.15 Diastereomers of 1,3-Dimethylcyclohexanecis-1,3-Dimethylcyclohexane is a meso compound. It is achiral because it has a plane of symmetry. trans-1,3-Dimethylcyclohexane exists as a pair of enantiomers.
Figure 8.16 Enantiomers of trans-1,2-Dimethylcyclohexanetrans-1,2-Dimethylcyclohexane exists as a pair of enantiomers. !ere is no a plane of symmetry.
Mirror
enantiomerstrans-1,2-dimethylcyclohexane
CH3
H3C
H3C
CH3
CH3
CH3
H3C
CH3
8.7 Cyclic Molecules with Stereogenic CentersCyclic Structures with Two Stereogenic Centers: Dimethyl Cyclohexanes
Figure 8.17 cis-1,2-Dimethylcyclohexane!e mirror images of cis-1,2-dimethylcyclohexane are not superimposable. However, chair-chair interconversion is very fast, so the enantiomers cannot be separated.
Mirror
CH3 H3CCH3 CH3
H3CCH3
very fast
8.7 Cyclic Molecules with Stereogenic CentersCyclic Structures with Two Stereogenic Centers: Dimethyl Cyclohexanes
Figure 8.18 General Method for Resolving Enantiomers
AR,ASRacemic mixture
XR
AR-XR AS-XR+Diastereomers
separateAR-XR AS-XR
cleave cleave
AR + XR AS + XR
separate separate
ASAROptically pure Optically pure
8.8 SEPARATION OF ENANTIOMERSGeneral Principles
8.8 SEPARATION OF ENANTIOMERSChiral Chromatography
(±)-mexiletine (an antiarrhythmic drug)
OCH2 CH
NH2
CH3
CH3
CH3
OCH2 CH
NH3
CH3
CH3
CH3
conjugate acid of mexiletine (pH 7)
O
column support (matrix)
NCO2
-
H
CO2-H
chiral ligand(S)-aspartate
8.9 CHEMICAL REACTIONS AT STEREOGENIC CENTERSPreview: Stereochemistry of a Substitution Reaction at a Stereogenic Center
C
H CH3
CH2(CH2)4CH3
HO Br !! !
Transition state for inversion of configuration
C Br
HCH3
CH3(CH2)5
(R)-2-bromooctane
NaOHCHO
H CH3
(CH2)5CH3
(S)-2-octanol
8.9 CHEMICAL REACTIONS AT STEREOGENIC CENTERSStereochemistry of a Free Radical Reaction
C CH2Cl
HCH3
CH3CH2
(S)-1-chloro-2-methylbutane
Br2 C CH2Cl
Br
CH3
CH3CH2light
+ C CH2Cl
CH3
BrCH3CH2
Figure 8.19 Free Radical Reaction at a Stereogenic Center A free radical intermediate is achiral because it has a plane of symmetry. A bromine molecule can therefore attack with equal probability from above or below the plane to give a 50:50 mixture of enantiomers. !e 2p orbital is half-occupied, and there is a 50% probability of "nding an electron above or below the nodal plane of the orbital.
C CH2ClCH3CH2
CH3
Br
C
Br
CH3CH2
CH3
CH2Cl
C
Br
CH3CH2
CH3
Br
BrBr
CH2Cl
Planar free radical
8.9 CHEMICAL REACTIONS AT STEREOGENIC CENTERSStereochemistry of a Free Radical Reaction
Figure 8.20 Stereochemistry of Markovnikov Addition of HBr to 1-ButeneA proton adds to the double bond of 1-butene to give an intermediate secondary carbocation. It is achiral because it has a plane of symmetry. Bromide ion can attack with equal probability from the top or the bottom to give a racemic mixture.
C CH3CH3CH2
HPlanar carbocation
C
Br
CH3CH2 CH3
H
(S)-2-bromobutane
C
Br
CH3CH2H
(R)-2-bromobutane
Br
Br
CH3
8.10 REACTIONS THAT PRODUCE STEREOGENIC CENTERSStereochemistry of Markovnikov Addition to Alkenes
Figure 8.21 Stereochemistry of Bromine Addition to Alkenes !e reaction of bromine with an alkene produces a bromonium ion intermediate. !is intermediate reacts with bromide ion in a process that results in net anti addition of bromine. !e stereochemical consequences for adding bromine to cis-2-butene and trans-2-butene are di"erent. cis-2-Butene yields a pair of enantiomers; trans-2-butene yields a meso compound.
Mirror plane
(2S,3S)-dibromobutane
C C
Br
H3C
H H
CH3
C C
Br
Br
H3C
CH3
HH
bromonium ion from cis-2-butene
a
Br
a
(2R,3R)-dibromobutane
C CCH3
Br
H3C Br
HH
(a)
Mirror plane
(2S,3R)-dibromobutane
C C
Br
H3C
H CH3
H
C C
Br
Br
H3C
HCH3
H
bromonium ion from trans-2-butene
a
Br
a
(2R,3S)-dibromobutane
C C HBr
H3C Br
CH3H
(b)
8.10 REACTIONS THAT PRODUCE STEREOGENIC CENTERSStereochemistry of Alkene Bromination
8.12 PROCHIRAL CENTERS
C
CH3
HO H
D
(S)-1-deuteroethanol
C
CH3
HO HR
HS
ethanol
C
CH3
HO D
H
(R)-1-deuteroethanol
add H from aboveC
CH3
OHHD
(R)-1-deuteroethanol
C
CH3
OD
1-deuteroethanol
add H from belowC
CH3
OHDH
(S)-1-deuteroethanol
oleic acid (R)-10-hydroxystearic acid
CH3(C6H2)6CH2
CCH2(CH2)6CO2H
OHH
C CCH2(CH2)6CO2H
HH
CH3(CH2)6CH2H2O
enzyme
HR
CH3
HS
CH3
OHH
(R)-2-butanol
D
CH3
H
CH3
OHH
(2R,3R)
H
CH3
D
CH3
OHH
(2R,3S)