Stereochirality R or S
Transcript of Stereochirality R or S
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SN2 Substitution, Nucleophilic, Bimolecular
Rate = k[CH3CH2OTs] [ Nu- ] ---------Bimolecular
Backside NucleophilicAttack InversioninConfiguration
ConcertedMechanism
Optically ActiveEnantiomericaly Pure
C Br
H3C
HC6H13
HO
CHO
CH3
H C6H13Br
CH3
HOC6H13
H
Transition StateR-(-)-2-BromooctaneS-(+)-2-Octanol
Inversion of Stereochemistry
C OTsH3C
H
HNu
CNu
CH3
H H
OTs
CH3Nu
HH
Transition State
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SN1 Substitution, Nucleophilic, Unimolecular( ) l 2 ( ) 2
+l-
Professor George OlahNobel Prize 1994
Carbocation is sp2-planar
CH3
CH3C
CH3
Cl
CH2
CH3H3C
+ Cl
Slow Step (RDS)
Aided by polar Solvent Stable 3o Carbocation
ions are stabilized via solvation
CH2
CH3H3C
Fast Step
HO
H
Front or Backside Attack
CH3
CH3C
CH3
O
tert-Butyl alcohol
H
H
CH3
CH3C
CH3
O H
- H+
C C
HC
H
H
> >
gr r l tr r l i g- l li t iti rg
mor t bl
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H3CH2CH2C
C BrH3CH2C
H3C CH2CH2CH3
CHO
CH2CH3CH3
H3CH2CH2C
C OH
H3CH2C
H3C
+
- HBr
S-3-Bromo-3-methylhexane
1:1 Mixture of R- and S-3-Methyl-3-hexanol
The Carbocation intermediate is
attacked by water from eitherside by the same rate
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STEREOCHEMISTRY
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Enantiomers are stereoisomers whose molecules arenonsuperimposable mirror images of one another
Objects that are superimposable on theirmirror images are said to be achiral
CH3
CH2
CHHO
CH3
CH2
CH
CH3 CH3OH Interchanging any two groups at a chiral
centre (stereocentre) that bears four
different groups converts one enantiomer
into another
I l t tr r l 3 at
CH3 C
OH
CH2 CH3
2-Butanol
H
ChiralCentre
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Nobel Prize2001
For synthesis of optically active compounds asymmetric synthesis
Professor William KnowlesProfessor oji Noyori
Professor K. arry ar less
C r
H3C
H
C6H13HO
CHO
CH3
H C6H13
r
CH3HO
C6H13
H
Transition tateR-(-)-2- romooctaneS-(+)-2-Octanol
InversionofStereoc emistry
SN
2
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One structure can be superimposed on another
If any of the groups
attached to thetetrahedral atom arethe same, the centreis achiral.
The ultimate way to test for
molecular chirality is to construct
models of the molecule and its
mirror image and then determine
whether they are superimposable
A molecule will not be chiral if it possess acentre or plane ofSymmetry
2-Propanol
CH3
C OHH
CH3
C
CH3
HHO
CH3
Screwdriver is achiralSocks are achiralGolf club is chiral
Gloves are chiral
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Properties of Enantiomers
Enantiomers have identical melting points and boiling pointsEnantiomers have identical solubilities in solvents
Enantiomers have identical spectra and refractive indexEnantiomers interact, and react with achiral molecules in thesame manner
Enantiomers interact andreact it ot er
c iral molecules at different rates
Enantiomers rotate lane- olarised lig t byequal amounts but in o osite directions
Plane-polarised lig t
Oscillationofelectrical fieldofordinary lig toccurs inall possibledirections
Polarimeter is a devise used to measure t e effect of lane-
olarised
lig t on
an
o tically active com ound
Chiral molecules areoptically active
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No Correlationbetweenthe directionofrotationofplanepolarisedlightandthe absolute configurationofa molecule
Clockwise Rotation(+) dextrorotatoryAnti-Clockwise Rotation(-) levorotatory
C
CH2CH3
H2CCH3
H
HOC
CH2CH3
H2CCH3
H
Cl
(R)-( )-2- et yl-1-butanol (R)-(-)-1-Chloro-2-methylbutanol
Same Configuration
Anequimolarmixture oftwo enantiomersiscalleda RacemicMixtureItisOptically Inactive
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H
O
S-(+)-Carvone
O
R-(-)-Carvone
H
rinciple component ofCaraway seed oil andresponsible for the
characteristic odour
rinciple componentof Spearmint oil andresponsible for the
characteristic odour
Receptor Sites in the Nose are hiral
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Enantiomers
Isomers that are non-superimposable
mirror-images
W
CXZ
Y
W
C XY
Z
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Locating a Stereocenter (Chiral
Carbon)
CH3 CH C
OH
OH
O
Lactic acid
*
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Locating a Stereocenter
CH3 CH2 CH2 CH2 CH2 C CH2 CH2 CH2 CH3
Br
H
*
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Locating a StereocenterO
CH3
H
*
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Locating a StereocenterH CH3
no stereocenter
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Locating a StereocenterCH3
Cl
no stereocenter
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Coniine: The Compound that
Killed Socrates
N
H
CH2CH2
CH3*
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Is there a stereocenter?
CH3
HO C CH
No e!
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Serine: one of the essential
amino acids
H2N CH C
CH2
OH
O
OH
*
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Carvone: mirror-image isomers
have different flavors and odors!O
CH3
C
CH3
CH2
*
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Muscone: the sex attractant of
the musk deer
CH3
O
*
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Cholesterol: how many
stereocenters can you find?
HO
CH3
CH3CH
CH3CH2
CH2 CH2
CHCH3
CH3
*
* *
*
*
*
*
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Crystals of Sodium Ammonium
Tartrate
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Optical Isomerism Difference in the way that isomers interact
with polarized light
Differences arise from molecular symmetry
properties
this is another type ofstereoisomerism.
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Ordinary Light
(showing magnetic and electric field vectors)
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Double Refraction
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The Picket Fence Analogy
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Optical Activity
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The Polarimeter
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Specific Rotation
[EA!tP
E
c l
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Configuration
Arrangement in space of atoms or groups
around the chiral part of the molecule
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Specification of Configuration
CC
112
2
33
44
R S
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Specification of Configuration SEQUENCE RULE 1: If the four atoms
attached to the chiral carbon are all
different, priority depends on atomicnumber, with the atom of higher atomic
number receiving the higher priority.
COROLLARY: If two atoms are isotopesof the same element, the heavier isotope is
assigned the higher priority
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I
CBrCl
F
I
CClBr
F
R S
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Specification of Configuration SEQUENCE RULE 2: If the relative
priority of two groups cannot be decided by
Rule 1, it shall be determined by a similarcomparison of the next atoms in the groups
(and so on, if necessary), working outward
in ranks from the chiral carbon. hydrogen atoms are ignored when the atoms
within a rank are compared to each other.
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Specification of Configuration
SEQUENCE RULE 3: A doubly-bondedatom A is treated as if there were two C-A
single bonds.
Priorities in the expanded representations
are assigned on the basis of Rule 2.
A
CC
A (C)
(A)
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REMEMBER!!!The atoms shown in parentheses (the
duplicate representations) do not exist!
They are written only for purposes of
assigning priorities.
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More...A triply-bonded atom A is treated as if there
were three C-A bonds, as in:
C A C A
(A)
(A)
(C)
(C)
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Corollary of Rule 3 If no other distinction can be made, a real
atom outranks a fictional atom.
NOTE CAREFULLY: This exception is
used only as a last resort!
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3-Chloro-2-butanol
C
C
CH3
CH3
OHH
ClH
C
C
CH3
CH3
HOH
HCl
C
C
CH3
CH3
HOH
ClH
C
C
CH3
CH3
OHH
HCl
enantiomers enantiomers
diastereomers
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Diastereomers Non-mirror-image stereoisomers
Differ in configuration about some, but not
all, chiral atoms
have different physical properties
can be separated by ordinary physical methods
differ in (R)/(S) sequence
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How Many Stereoisomers Are
Possible?
number of stereoisomers = 2
n
,
where n = number of chiral atoms
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2,3-Dichlorobutane
C
C
CH3
CH3
ClH
ClH
C
C
CH3
CH3
HCl
HCl
C
C
CH3
CH3
HCl
ClH
C
C
CH3
CH3
ClH
HCl
enantiomers
meso
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n = 1
n = 2 or more
Is there a
stereocenter?ACHIRAL
NO
STEREOISOMERS
YES
ENANTIOMERS
mirror-image
DIASTEREOMERS
OPTICALLY
ACTIVE meso
always plane of
symmetry
no plane of
symmetry
non-mirror-image
OPTICALLY
INACTIVE
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Glyceraldehyde
(an aldotriose)
C
C
CH2
H OH
OH
OH
C
C
CH2
OH H
OH
OH
(+) (-)
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The Aldotetroses
C
CH2OH
OHH
OHH
OHC
CH2OH
HOH
HOH
OH
C
CH2
OH
HOH
OHH
OH
C
CH2
OH
OHH
HOH
OH
(-) (+)
(-) (+)
Erythrose
Threose
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The AldopentosesCHO
CH2OH
OHH
OHH
OHH
CHO
CH2
OH
HOH
HOH
HOH
CHO
CH2
OH
HOH
OHH
OHH
CHO
CH2
OH
OHH
HOH
HOH
CHO
CH2
OH
OHH
HOH
OHH
CHO
CH2
OH
HOH
OHH
HOH
CHO
CH2OH
HOH
HOH
OHH
CHO
CH2
OH
OHH
OHH
HOH
Rib s Ar bi s
X l s L x s
(-) (+) (-) (+)
(+) (-) (-) (+)
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The AldohexosesCHO
CH2OH
OHH
OHH
OHH
OHH
CHO
CH2OH
HOH
OHH
OHH
OHH
CHO
CH2OH
OHH
HOH
OHH
OHH
CHO
CH2OH
HOH
HOH
OHH
OHH
CHO
CH2OH
OHH
OHH
HOH
OHH
CHO
CH2OH
HOH
OHH
HOH
OHH
CHO
CH2OH
OHH
HOH
HOH
OHH
CHO
CH2OH
HOH
HOH
HOH
OHH
(+)- All s (+)- Altr s (+)-Gluc s (+)-Mannos
(-)-Gulos (-)-Idos (+)-Galactos (+)-Talos
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The Aldohexoses (the other half)
(-)-Allose (-)-Altrose (-)- l cose (-)- annose
(+)- ulose (+)-Idose (-)- alactose (-)-Talose
CHO
CH2
OH
OH H
OH H
OH H
OH H
CHO
CH2OH
H OH
OH H
OH H
OH H
CHO
CH2
OH
OH H
H OH
OH H
OH H
CHO
CH2
OH
OH H
H OH
H OH
OH H
CHO
CH2
OH
H OH
OH H
H OH
OH H
CHO
CH2OH
OH H
OH H
H OH
OH H
CHO
CH2OH
H OH
H OH
H OH
OH H
CHO
CH2OH
H OH
H OH
OH H
OH H
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