Dr.

Deepak R Nagargoje,
Astt. Professor in Chemistry,
MPASC College, Panvel,
Dist. Raigad (Maharashtra)
 Introduction
Most of the molecules of importance to living systems are
enantioenriched or enantiopure

Examples include:
Amino Acids
Sugars
 Proteins
Nucleic Acids
Vitamins
Terpenes
Alkaloids and
Steroids.
Some examples of Enantiomers

R(+) limonene S(-) limonene

smell of oranges smell of lemons

O NH2 O
H2N HO
OH NH2
O NH2 O
Bitter Sweet
Asparagine
Methods of isolation of enantiopure compounds

 From natural products

 by resolution of racemic mixtures

 few laboratory controlled enzymatic reactions

 Asymmetric synthesis or stereoselective synthesis

What is asymmetric synthesis?
Asymmetric synthesis or Stereoselective synthesis
A chemical reaction (or reaction sequence) in which one or more
new elements of chirality are formed in a substrate molecule and which
produces the stereoisomeric (enantiomeric or diastereoisomeric) products
in unequal amounts. Traditionally called asymmetric synthesis.
H CH3 H CH3
Ru cat. COOH COOH
COOH +
H2 MeO
MeO MeO

ee 97% ee 3%

What do we mean by asymmetric synthesis – a reaction that creates one

configuration of new stereogenic elements by the action of a chiral reagent
chiral auxillary or solvent acting on heterotopic (enantiotopic or
diastereotopic) faces, atoms or groups of a substrate.
Asymmetric Methods for Obtaining Enantioenriched
Compounds
1. Synthesis from enantioenriched Chiral Pool starting
products
The chiral pool is that collection of cheap, readily available pure
natural products, usually amino acids or sugars, from which pieces containing
the required chiral centres can be taken and incorporated into the product
CO2Me O CO2Me HOOC
COOH
Ph
+
Ph
N COOH NH2 NH2
H

NH2
2. Synthesis using enantioenriched Chiral Pool auxiliaries
The chiral auxiliary is temporarily incorporated into an organic
synthesis which introduces chirality in otherwise racemic compounds.
O O O
O O LiOBn
+ HN O Base N O
Cl Et2AICl N O OBn
O O

3. Enantioselective catalysts
Enantiomeric Excess (% e.e.)
Enantiopurity is usually reported in terms of “enantiomeric excess”
(e.e.).
% e.e. = Major - minor
------------------------- x 100
major + minor
Some examples of Asymmetric
synthesis
Sharpless Asymmetric epoxydation

Ti(O-iPr)4 Ti(O-iPr)4
HO t-BuOOH O O
HO HO t-BuOOH HO
(+) DET (--) DET
OH OH
CO2Et CO2Et
EtO2C EtO2C
OH OH

Nobel Prize (2001) for catalytic asymmetric oxidation

Other reactions

1) Asymmetric Aldol and related reactions

2) Asymmetric Diels-alder reaction
3) Asymmetric dihyxoxylation, aminohydroxylation etc.
4) Asymmetric reductions
5) Asymmetric transfer hydrogenation
6) Asymmetric hydrosilation reactions
7) Asymmetric reactions for synthesis of natural products
References
1) www.iupac.org

2) Principles and Applications of Asymmetric Synthesis, Guo-Quin Lin, Wiley

Interscience.

3) Organic Reaction Mechanism by Prof. A. K. Parasher, New Age

Publishers, New Delhi

4) Organic Chemistry , J. Clayden et al, Oxford University

Press, Manchester
Thank you