Chapter 5 Stereochemistry

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Chapter 5 Stereochemistry
General definitions
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chiral - the mirror image of an object produces
another object which is not superimposible on the
original. From the Greek word for
handed. achiral - something that is not chiral
enantiomers - pairs of molecules that are mirror
images of each other and are nonsuperimposible
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• chiral molecules
• 1. two representatives -
• 3-methylhexane
• 3-methylpentane

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3-methylpentane is achiral
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3-methylhexane is chiral
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Generalization
Compounds with four different groups around a
carbon atom generate a chiral molecule. The
carbon atom with the four different groups is
said to be a chirality center or a stereogenic
center.
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2. Elements necessary for an achiral
molecule. a. an internal mirror plane of symmetry
internal mirror plane
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b. inversion center
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3. Telling the difference between two
enantiomers a. plane polarized light
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If one enantiomer rotates plane polarized light
by x in a clockwise direction, then the other
enatiomer will rotate plane polarized light by x
in the counterclockwise direction. d -
dextrorotatory - () enantiomer ? rotate
clockwise l - levorotatory - (-) enantiomer ?
rotate counterclockwise
racemic mixture - a 5050 mixture of two
enantiomers for example the (d,l) or
(,-)-3-methylhexane mixture
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b. another chiral molecule that interacts with
the two enantiomers
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the most important example is enzymes in cells
R ? good - morning sicknes S ? bad - birth
defects
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4. Absolute configuration - the
Cahn-Ingold-Prelog scheme a. assign a priority
number to the four groups around the chiral
center 1highest, 4lowest priority i. atomic
number of the atom directly connected to the
chiral center ii. in case of ties- go to
next set of atoms
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one atom of higher priority takes precedence over
any number of others
note
iii. for multiple bonds - break and add imaginary
atoms as follows
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b. Orient the molecule so the group with lowest
priority, 4 Is in back of the plane of the paper.
Now rotate from highest,1 to 2 to 3.
If the rotation is clockwise then the
configuration is R - rectus If the
rotation is counterclockwise, then the
configuration is S - sinister
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5. conformationally mobile systems
Can we make one enatiomer of gauche butane??
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An achiral intermediate or transition state
that is energetically accessible always leads to
racemization.
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Another example The sad story of
cis-1,2-dimethylcyclohexane
e, a
a, e
enantiomers
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B. Fischer Projections - a lazy mans way to
handle stereochemistry - a poor mans
representation of
3 - D
BE VERY CAREFUL WITH THIS!!!!!

• General construction
• convention 1

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Mirror plane
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NOTE when viewing from the backside, the sense
of rotation reverses!
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Lets flip the structure

• So the moral of this story is as follows
• A 90 rotation or flipping the structure around
  either axis will cause it to be converted into
  its enantiomer.
• 2. Rotation by 180 keeps the same configuration.

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The virtue of Fischer projections is that they
can be easily used for molecules with more than
one chiral center. Lets take 2, 3-dibromobutane
as an example
Is it chiral?
This molecule is still not superimposible on the
first one by sliding it, so it must be an
enantiomer
mirror plane
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What about this configuration for
2,3-dibromobutane??
mirror plane
This molecule is superimposible on the first one
by sliding it, so it must be identical to the
first.
Therefore this molecule is NOT chiral!
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2. Assigning R, S configurations - within the
Fischer projection
Convebtion 2 a. Always put the lowest priority
group in the horizontal position. b. Going from
priority 1 to 2 to 3, a rotation counterclockwise
is R and a rotation clockwise is S.
THIS IS EXACTLY OPPOSITE TO DOING THE
CONFIGURATION ASSIGNMENT IN THE ACTUAL 3-D
SPACE!!!!
Lets take a few cases---
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therefore
and
Now - what is the relationship between the R,R
and S,S configurations and the R,S one??
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C. Compounds with more than one center of
chirality. For 2,3-dibromobutane there are three
different steroisomers, in general terms we
have
So there are 2n possible stereoisomers if
there are n chiral centers. However, this is not
true for molecules that have an internal mirror
plane of symmetry -
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Internal mirror plane of symmetry
In reality a center of inversion
Fischer projections are most useful for sugars
glucose
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D. Resolution of enantiomers - forming two (or
more) chiral centers is the whole idea how we can
tell or separate one enatiomer from another
1. They form diasteromeric complexes with the
chiral agent i ) Consider AR and AS to be two
enantiomers. ii ) BR may be a chiral solvent, a
chiral substrate, or even just plane polarized
light that propagates in a clockwise (or an
anticlockwise) direction. AR and AS BR ?
ARBR and ASBR these are diastereomers
2. Diastereoisomeric interactions are used to
separate enantiomers. If, for example, A is a
racemic acid and B is a chiral base (a natural
product), the salts that are produced can be
expected to have different solubility properties.
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Pharmaceutical Industry Marketed
Compounds Total 1850
Natural Semisynthetic 520
Synthetic 1370
achiral 6
chiral 517
achiral 788
chiral 528
racemate 8
single enantiomer 509
racemate 467
single enantiomer 61
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turpentine oder from fir trees
orange oder from oranges
caraway oil
oil of spearmint
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E. Summary

• Definitions
• a. chiral/ achiral
• b. diastereomer/ enantiomer
• c. configuration/ conformation
• d. mirror plane/ center of inversion
• 2. Absolute configuration know
  Cahn-Ingold-Prelog rules
• a. determine priority of groups around chiral
  center
• b. determine R, S configuration
• 3. More than one center of chirality
• a. Fischer projections
• i) manipulations, ie inverting, flipping,
  rotating
• ii) determining R, S
• b. Diastereomers - resolution of enantiomers