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Stereochemistry Basic Concepts Useful Notes For Students
Stereochemistry Basic Concepts Useful Notes For Students
Stereochemistry Basic Concepts Useful Notes For Students
Definition:
It is the study of molecules in 3 dimensional arrangement in the space.
HO2C H H H
trans isomer cis isomer
The cis isomer (maleic acid) is toxic, whereas the trans isomer (fumaric
acid) is an essential metabolite for plants and animals.
Chirality
Chirality means “handedness”.
Achiral objects have mirror images that are identical to the object.
H H H H Cl H H Cl
Cl Cl Cl Cl H Cl Cl H
cis isomer is achiral trans isomer is chiral
CH3 CH3
H H
H3CH2C Br Br CH2CH3
A A
B B
D C C D
H H
Cl Cl
(Note that the absence of a mirror plane does not imply chirality).
The (R) and (S) assignments are designated via the Cahn-Ingold-Prelog
Convention.
Each chiral center is designated either (R) or (S).
1) Assignment of Priority
We look at the atoms directly bound to chiral carbon.
(a) Atoms with higher atomic numbers receive higher priorities.
13 12
I>S>O>N> C> C > Li > 3H (T) > 2H (D) > H
(b) In the case of the same atoms being bound directly to the chiral
carbon, we go to the next atoms along the chain.
-CH2Br > -CHCl2 > -C(CH3)3 > -CH(CH3)CH2F > -CH(CH3)2 > -CH2CH3
(c) Double and triple bonds are treated as if each bond were to a separate
atom. (Imagine that each bond is broken and that the atoms at both
ends were duplicated).
(R) enantiomer
1 1
2 * C*
C 2 3
3 4
(S) enantiomer
Consider the naturally occurring amino acid, alanine, and its
enantiomer.
(1) (1)
NH2 NH2
(2) (2)
*C CO2H HO2C
C*
H CH3 H3C H
(4) (4)
(3) (3)
unnatural natural
alanine alanine
(1) (1)
NH2 NH2
C* C*
H3C CO2H HO2C CH3
(3) (2) (2) (3)
Optical Activity
Enantiomers have the same Boiling points
Melting points
Density.
Almost all their physical properties are identical, but one exception is
their effect on plane polarized light.
Enantiomeric compounds rotate the plane of polarized light in equal
but opposite directions.
Note: There is no relationship between (R) and (S) and the direction of the
rotation of plane polarized light. (R) does not mean d and (+).
(R) and (S) are just names from the CIP convention. (+) and (-) are
experimentally observed physical properties.
CH3 CH3
O O
H3C H H CH3
CH2 H2C
(+)-carvone (-)-carvone
caraway seed spearmint
Absolute Configuration
The absolute configuration of a molecule is the detailed stereochemical
picture including how the atoms are arranged in space.
Any reaction that uses optically inactive reactants and catalysts cannot
produce a mixture that is optically active. Any chiral products formed
will be formed as a racemate.
This is demonstrated by the hydrogenation of 2-butanone:
H
CH3CH2
CH3 O-H
(R)-2 butanol
H H equal
CH3CH2 amounts
C O (racemate)
CH3
H H (S)-2 butanol
CH3 O-H
CH3CH2
H
There is no energy difference for the attack from the top or bottom face,
and there is no energy difference in the (R) or (S) products.
The optical purity is defined as the ratio of the observed optical rotation
of the mixture to the rotation of a pure enantiomer. It is usually
expressed as a percentage.
If the ring was flat and planar, then an internal plane of symmetry would
exist, and this molecule would therefore be achiral.
H H
Br Br
But the ring is not planar, it is puckered into a chair conformation, with
one Br axial, and one equatorial.
H H
Br Br
H H
Br Br
Conformational Enantiomerism
Certain molecules are so bulky or strained that they cannot easily
convert from one chiral conformation to its mirror image conformation
(the opposite of cis-1,2-dibromocyclohexane).
(S) (R)
Br Br
Br Br
X
I I
I I
This is more common for strained ring systems and /or bulky
substituents.
Allenes
This is a class of compounds that contain a C=C=C bonding unit.
H H
C C C
H H
The middle C is sp, and the outer two C’s are sp2 hybridized.
The two contiguous bonds must lie perpendicular to each other for p
orbital overlap – thus the ends of an allene are perpendicular.
H CH3 H3C H
C C C C C C
H3C H H CH3
Enantiomers
Fischer projections
We have already seen 3 dimensional representations using wedges,
Sawhorse and Newman projections.
These become less convenient for molecules with many chiral carbon
atoms, and we typically use Fischer Projections.
Fischer Projections
A A A
D
B
= B C = B C
C
D
D
View
Fischer projections are drawn with a cross, with the chiral atom at the
center of the cross.
The horizontal lines represent wedges (bonds) coming out of the plane of
paper.
The vertical lines represent dashed lines (bonds) going into the plane of
the paper.
(“Bow-tie” convention).
CO2H CH3
CH3 CO2H
H OH HO H
(R) (R)
View View
CO2H H
CH3 OH
H OH H3C CO2H
(R) (S)
View View
CO2H CO2H H H
H OH = H OH 90o H3C CO2H = H3C CO2H
H3C OH
CH3 OH
Fischer projections have another rule which helps with the above laws:
The carbon chain is drawn along the vertical line of the projection, with
the most highly oxidized carbon substituent at the top.
(R)-1,2-propanediol
CO2H CO2H
H OH HO H
CH3 CH3
(R) lactic acid (S) lactic acid
Examples:
CH2OH CH2OH CH3
H OH HO H 180o H OH
CH3 CH3 CH2OH
CH3
H OH
CH3
Recall that since the C chain is arranged vertically, the lowest priority
group (usually H) will be on the horizontal axis (which means it is
sticking out toward us).
(2) (2)
CHO
CHO
H OH (1)
HO CH2OH
(1) CH2OH
(3) (3)
Diastereomers
Stereoisomers are molecules that have atoms bonded together in the
same order, but differ in how the molecules are directed in space.
Enantiomers are mirror image isomers. All other stereoisomers are called
diastereomers.
Geometric Isomers
For example, 2-butene.
H CH3 H H
trans cis
Seen these before. They are not mirror images of each other – not
enantiomers.
(3)
CH3
H Br (1) = (S) configuration at C-2
(2)
H Cl
CH3
Enantiomers Enantiomers
We can also say (2S, 3R) is a diastereomer of (2S, 3S) and (2R, 3R), and
(2S, 3S) is a diastereomer of (2S, 3R) and (2R, 3S).
Meso Compounds
Previously we saw all the permutations (4) for a molecule with two chiral
centers.
This gives the maximum possible number of stereoisomers that can exist
– but often if the molecule is highly symmetrical, some of these
stereoisomers are actually the same compound.
The enantiomer pair are termed the (±) diastereomer (or dl),
The ‘same compound’ pair are called the meso diastereomer.
In a lab it is different.
O H2, Pt H OH HO H
H3C CH2CH3
H3C CH2CH3 H3C CH2CH3
2-butanone (R)-2-butanol (S)-2-butanol
CO2H
H OH (R,R)-(+) tartaric
HO H acid
CO2H
H+
O CH2CH3 CH2CH3 O
O H H O
H OH CH3 CH3 H OH
HO H HO H
CO2H CO2H
(S)-2-butyl-(R,R)-tartrate (R)-2-butyl-(R,R)-tartrate
H+ H+
CH2CH3 CH2CH3
HO H H OH
CH3 CH3
(S)-2-butanol (R)-2-butanol
CO2H CO2H
H OH H OH
HO H HO H
CO2H CO2H
Acid hydrolysis cleaves each ester back to an optically active alcohol and
carboxylic acid.
Stereochemistry of Reactions
This is the study of what happens when chiral compounds react. Studies
with chiral compounds can reveal a vast amount of information about a
reaction mechanism.
Inversion of Configuration
If a reaction takes place at a chiral center and the product has the
opposite stereochemistry of the reactant, it has proceeded with inversion
of configuration.
H3C O CH3
_
H O S CH3 HO H
H O
CH3CH2 O CH2CH3
(R)-2-butyltosylate (S)-2-butanol
-O3S CH3
Racemization
Many reactions will display neither clean (total) inversion or clean
retention of configuration. Such reactions are called racemizations.
If all optical activity is lost it is a complete racemization, if some optical
activity remains, it is a partial racemization.
CH3CH2
CH(CH3)2
H3C O-CH2CH3
Br CH3CH2
(R) H3C CH(CH3)2
-Br- -H+
(S)
Inversion
CH3CH2 top
+
H3C C CH(CH3)2
H-O-CH2CH3
(planar) bottom
H3C
-H+ CH(CH3)2
CH3CH2
O-CH2CH3
(R)
Retention
Retention of Configuration
This is the least common type of reaction. When a product maintains the
same configuration as the reactant, it proceeds with retention of
configuration.
CH3CH2
H Cl
OH
H3C S O
Cl
-HCl
Cl
CH3CH2 Slow CH3CH2 Cl
H S O H +
O _ S O
H3C H3C O
Fast
CH3CH2
H Cl +SO2
H3C
Retention
The product is not racemized since the slow C-O bond breaking and fast
Cl attack do not allow the cation to achieve a planar (achiral)
arrangement.
Reactions that do not Involve the Chiral Atom
Typically, if bonds directly to the chiral atom are not broken or formed
during the reaction, the configuration will remain unchanged.
CH3CH2 _ H CH3CH2 H
-I- H
H O H I H O
H3C H H3C H
(S)-2-butoxide (S)-2-methoxyethane
The four bonds to the chiral C atom are unchanged, and the
configuration is the same.
Asymmetric Induction
This is the use of an optically active reagent or catalyst to convert an
achiral reactant into a chiral product.
H H2, Pt OH H H H
O
CH3 H CH3 OH CH3
minor major
The two faces of attack are not the same since the methyl group
sterically hinders one face.
The chiral carbon atom communicates its chirality to the new center.