Enantioselective Synthesis
Racemic Synthesis
How to obtain single
enantiomers?
Resolution
Racemic Synthesis
Resolution
Chiral resolution
Chiral pool
Chiral pool
Chiral pool
Chiral pool
Enantioselective Synthesis
Principles
Asymmetric synthesis
Chiral reagents Chiral auxiliaries Asymmetric catalysis
Organocatalysis
Transition metal
catalysis
Biocatalysis
Chiral Auxilaries
Asymmetric catalysis
Organocatalysis
Lewis acid Lewis base BrØnsted acid Ion pairs
How to determine
enantioselectivity?
❑ A chiral molecules and its mirror image are
called a pair of enantiomers
❑ Enantiomers have identical chemical and
physical properties (IR, NMR, m.p, mass spectra,
etc.)
❑ Except for their ability to rotate plane-polarized
light (+/-) by equal amounts but in opposite
directions
❑ When the light is polarized through a
solution containing a compound with
optical activity it causes the polarized light
to rotate. When a compound does not
rotate polarized light it is said to have no
optical activity (optically inactive)
❑ The rotation of the polarized light can be
clockwise (+) or counterclockwise (-).
20
Optical Activity
where a = specific rotation
(observed ) c = concentration in g/mL
[ ] = l = The length of sample tube in dm
c l a (observed) = observed rotation
❑ The observed angle of rotation depends on :
▪ Optical activity
▪ Concentration of the sample
▪ The length of sample tube
❑ Specific rotation [] can be used as the characteristic physical properties of a
compound if: The angle of rotation was observed using a sample tube
length of 10 cm and concentration of 1 g/mL.
Optical
Activity
A solution of 2.0 g (+)-glyceraldehyde in 10.0 mL aquadest was placed in a 100
mm polarimeter tube. Using a sodium D line beam, gives a rotation of 1.74o at 25
oC. Calculate the specific rotation of (+)-glyceraldehyde.
Solution:
1m 10 dm
Observation → (obs) = 1.74o l = 100. mm = 1.00 dm
1000 mm 1 m
2.0 g
c= = 0.20 g mL
10.0 ml
(observed )
Determination of []: [ ] =
c l
+ 1.74
[ ] = = 8.7 o
0.20 1.00
Optical
Activity
Racemic mixture:
equal amounts of (+) and (-) enantiomers
– rotation is 0o
Exercise :
0.5 g (-) epinephrine-HCl in 10 mL H2O measured in 20 cm
cell (25o/D) obs= - 5.0o.
a. Calculate the specific rotation of this compound.
b. Determine the configuration of this compound
c. Write the correct name for this compound, including the
absolute configuration and its optical activity
II. Enantiomeric excess (ee) → optical
activity
❑ When dealing with a mixture of enantiomers, it is
essential to describe the composition of the
mixture and the degree to which one enantiomer
is in excess.
❑ The most common designation is enantiomeric
excess (ee)
Diastereomeric excess → de
Enantiomeric excess (ee)
II. Enantiomeric excess (ee) → Chiral Shift reagent in NMR
✓ However, polarimetry is not very
sensitive, especially if is relatively low.
Several other methods for determining
enantiomeric purity have been
developed. One of the most frequently
used in organic chemistry involves NMR
spectroscopy with chiral shift reagents.
✓ Chiral shift reagent making
diastereomeric relationship with
enantiomers upon interaction.
✓ Mosher’s reagent enables the
determination of absolute
stereochemistry of secondary
alcohols, thiols and amines.
Chiral reagents
Chiral reagents
Chiral reagents
Chiral reagents
To be continued
