Stereochemistry

Str u ctu r a l isom er s h ave d iffer en t con n ectivities. Ster eoisom er s ar e isom er s
th at h ave th e sa m e con n ectivity b u t a d iffer en t ar r an gem en ts of atom s in
sp ace.
H H H CH3
C C C C
H3C CH3 H3C H

H CH3 H CH2CH3
C C C C
H3C CH2CH3 H3C CH3

Z - Zusammen E - Entgegen
H CH3
C C
H3C CH2CH3

The Cahn-Ingold-Prelog Rules for prioritizing substitutents:

1) The higher the atomic no., the higher the priority.

2) For atoms of identical Z, the heavier (isotope) has higher priority.

13
C > 12 C, 3H > 2H > 1H

3) If the atoms attached are the same, then move out to the next shell of atoms one
bond further.
CH2CH3
C
CH2OH

CH2F
C
CH2CH2Br
 H
OCH3
C
OCH3
C
C
H OCH3
H

CF3
C
CH2SH

H3C CH2OH
C C
H C H
O

CN

O
C
OH

CH3
C C H vs C
CH3
CH3
Molecules are identical if (in the same conformation) they are superimposable.

CH3 O
Cl H Cl
C O
H3C
C CH3
H CH3
If the connectivity differs, then they are structural isomers. If the connectivity is
the same but the molecules are not superimposable, then they are stereoisomers.

H H

Cl
C CH
3 H3C C Cl
CH2CH3 H3CH2C

Are these two molecules the same?

What happens when we switch two groups on an assymetric carbon?

Enantiomers:

Chiral:

An asymmetric or stereogenic carbon:

Any molecule with a single asymmetric carbon atom

Configuration:
Enantiomers have identical physical properties in all respects

except that they rotate plane-polarized light in opposite directions.

Solutions that rotate plane-polarized light are said to be "optically active".

OH OH
+/- C C
H3C H CH2CH3
CH2CH3 H3C
H
d

A 50/50 mixture of a molecule and its enantiomer do not rotate plane polarized
light. These are called "racemic" mixtures.
 The D/L Convention of Fischer

H
All sugars with the same absolute configuration next to
CH2OH the CH2OH group are "D". Those with opposite
HO absolute configuration are "L"
CHO
D-Glyceraldehye

How do we name compounds to reflect their absolute configurations?

1 4 4
1 2 1 3

C C
2 3
4 3 2

CO2H CH2OH
C C
H H
H3C Cl H3C Cl

H CH3
H3C Br
C C Cl
H
HO CH3

H Br

O
 Fischer Projections: a short hand notation for showing absolute
configurations.

90°
CHO CHO H H
H OH H OH HOH2C CHO HOH2C CHO
CH2OH CH2OH OH OH
180°
CHO
HO H
CH2OH CH2OH CH2OH
HO H HO H
CHO CHO

A 9 0 ° or 2 7 0 ° r ota tion of a Fisch er p r ojection ...

A 1 8 0 ° r ota tion of a Fisch er p r ojection ...

Fisch er Pr ojection s wer e d evelop ed to a id in d r a win g m olecu les(su ga r s,

actu ally) with m a n y ch ir a l cen ter s. It is ea sy to sp ot en a n tiom er s a n d
su p er im p osa b le m olecu les wh en th ey ar e d r awn as th ese p r ojection s.

CHO CHO CH2OH CH2OH

HO H H OH HO H H H
HO H H OH HO H HO OH
CH2OH CH2OH CHO CHO
 Another way to assign R or S: The Parity Rule

Requires that a molecule be drawn such that the configuration is clear and
unambiguous.
Advantage: molecule need not be redrawn or mentally manipulated.

1) Assign priorities. 2) Write down the priority number of any substituent that is
clearly pointing toward you, followed the remaining priority
numbers in (always) clockwise order beginning anywhere you
CH3 want.
Cl

O 3) Take the four digits you have collected. Look at the first
number and determine how many numbers to its right are smaller.
Do this for the second number and the third, and sum the results.

4) If the sum is odd, the center is S. If the sum is even, the center is R.

H3C Br
H
C C
H
HO CH3

Great for Fischer Projections!!

HO CH2OH

CHO
 H H
H3C Br Br CH3
C C C C
H H
HO CH3 H3C OH

Br Br
H3C H CH3
H
C C C C
H H
HO CH3 H3C OH

Stereoisomers that are not enantiomers are called:

H H
H3C Br Br CH3
C C C C
H H
Br CH3 H3C Br

Br Br
H3C H CH3
H
C C C C
H H
Br CH3 H3C Br
 H

OH
H

OH
H

HO
H

OH

H
H
HO
HO

Cl Cl
C C C
H H
HO

OH
BINAP

CH3CH2 Ph CH3
N
N
CH3CH2 Ph CH3

CH3CH2 Ph CH3

CH3CH2 Ph O
 Stereochemistree
So, you've got two molecules and you want to know their relationship.

Is the connectivity
the same?

Yes No

Are they Constitutional

superimposable? Isomers

Yes No

Identical They are stereoisomers.

Molecules Are they mirror images
of each other?

Yes No

Enantiomers Diastereomers
 Carbohydrates or Sacharides

These exist in two interconverting isomeric forms - a chemical equilibrium known as a

tautomerism. This is further classified as a ring-chain tautomerism since one "tautomer" is
cyclic and one is acyclic. In order to better compare the stereochemical relationships of
carbohydrates, they are often drawn in the acyclic form as a Fischer projection.

H H
CH2OH CH2OH
HO OH HO
H O
H
HO H H
O HO OH
C
H OH OH
H H H
CHO CHO
H H
H OH HO H CH2OH
CH2OH
HO HO H H OH O OH
O
H H
H H OH HO H H OH
HO OH HO
H OH HO H HO
H OH H
H CH2OH CH2OH H
β-D-glucose β-L-glucose
H
CH2OH CHO
HO O
H α-D-glucose HO H
D-Mannose
HO H HO H
H
OH H OH
H OH
H OH
CH2OH
OH CHO CHO
CH2OH H OH H OH
H O
H HO H H CH2OH H OH
HO H OH O
HO H H H OH
HO H
H OH OH
H H OH CH2OH
β-D-galactose HO H
CH2OH
D-ribose
 Amino Acids

H2 NCH2 COOH H2 NCHCH3 COOH

Glycine Alanine
O
O H
C OH COOH C
H2N C H H2N H H C OH
CH3 D-Glyceraldehyde
CH3 CH2OH
L-alanine

COOH COOH
H2N H2N C COOH
C
H H H2N C
CH2SH CH2OH H
Cysteine Serine CH2
COOH Note that these natural amino
H2N C acids all have the same spatial N H
orientation of their substituents.
H These are called L-amino acids not
CH2 because they all rotate plane-polarized
light in a levorotatory fashion (they do Tryptophan
not) but because of their structural
relationship to D-glyceraldehyde which
N N H is dextrorotatory. Blame the biochemists
for this confusing foolishness.
Histidine

Proteins (and therefore enzymes) are polymers made from many amino acid units taken
from the pool of ca. 20 essential amino acids.
O R H
H2N C OH A dipeptide.
N C
H R H O
O R H H O R H H O R H
H2N C N C N C OH
N C N C N C
H R H O H R H O H R H O
A poly peptide.
 Stereochemistry and reactions

CH2 CH3
H+
C + H2O C
H CH2CH3 H CH2CH3
OH

H H
C C
H3CH2C Cl CN CH2CH3 Cl
NC
H3C CH3

H CH3
CH2
C C
H3CH2C OH C H CH2CH3 + H2O
Cl
H3C H CH2CH3 OH

H CN

H CN

CN H

The enzyme catalyzed hydrolysis of a triglyceride (a lipid) to a diglyceride. Note that

the triglyceride is achiral while the diglyceride is chiral.

CH2(CH2)16CH3 CH2(CH2)16CH3
O C HO C
H2C
O Hydrolase O
Enzyme OH
HC O C CH2(CH2)16CH3 H2C
H2C O H C O C CH2(CH2)16CH3
O C
O CH2(CH2)16CH3 H2C O
O C
Tristearylglycerol O CH2(CH2)16CH3

You cannot make one enantiomer of a product preferentially starting only with
achiral molecules. In other words, you can only make optically active products
using optically active reagents (including catalysts). There are no known exceptions
to this. Or are there?
Enzymes and selectivity

Substrate
Blobase Enzyme
Enzyme/substrate complex

Products

Wrong absolute
configuration (and therefore
also the wrong shape)
Wrong shape
 Where do we get chiral, optically pure chemicals?

The chiral pool...

CO2H
HO H
H OH
R-Pinene CO2H O
D-Tartaric Acid R-+-Camphor

Chiral Resolution...

Assymetric Catalysis

Ph Ph
P O
O
S-BINAP Ru
P O
O
Ph Ph

CO2H CO2H