asymmetric syntheasis

1. AMAL T. BABU
1ST MSc. CHEMISTRY
SACRED HEART(AUTONOMOUS) COLLEGE, THEVARA

2. INTRODUCTION
• CHIRALITY OF NATURE
• LEMONS AND ORANGES
• EXAMPLES: ASPARTAME,
PENICILLAMINE,DOPA
R-(+) LEMONENE
L-(-) LEMONENE

3. Some examples
R- DOPA (TOXIN)
ASPARTAME

4. ASYMMETRIC SYNTHESIS
 Asymmetric synthesis or Stereo selective synthesis
chemical reaction (or reaction sequence) in which one or
more new elements of chirality are formed in a substrate
molecule and which produces the stereo isomeric
(enantiomeric or diastereo isomeric) products in unequal
amounts.
 Production of a specific enantiomer from achiral compound
or racemic mixture
 Absolute synthesis, partial asymmetric synthesis
 enantio specific synthesis

5. PRINCIPLE OF ASYMMETRIC SYNTHESIS
 achieved by using a chiral feature that favours
the formation of one enantiomer over another
via interactions at the transition state
 Kinetical determination.
Fig.1
Fig.2

6. ASYMMETRIC INDUCTION
 the preferential formation in a chemical reaction of one
enantiomer or diastereoisomer over the other as a result of
the influence of a chiral feature present in the substrate,
reagent, catalyst or environment
Asymmetric
induction
Internal asymmetric induction: chiral center
bound to the reaction center used
Chiral pool synthesis
Relayed asymmetric induction: chirality
introduced in separate step
Chiral auxiliaries
External asymmetric induction: chiral
information at transition state
Chiral catalysts

7. DIFFERENT APPROACHES
• Chiral pool synthesis
• Chiral auxiliaries
• Chiral reagents, Chiral catalysts and chiral ligands

8. CHIRAL POOL SYNTHESIS
 simplest and oldest approaches for enantioselective synthesis
 Uses an enantiomerically pure natural product as a starting
material,
 The chiral pool—Nature’s ‘ready-made’ chiral centres :pure
natural products, usually amino acids or sugars, from which
pieces containing the required chiral centres
can be taken and incorporated into the product.
 Aspartame from s- phenylanine and s- aspatic acid

9. CHIRAL AUXILIARIES
 An enantiomerically pure compound (usually derived from a simple natural
product like an amino acid), called a chiral auxiliary, is attached to the
starting
material.

A diastereoselective reaction is carried out, which, because of the
enantiomeric purity of the chiral auxiliary, gives only one enantiomer of the
product.

The chiral auxiliary is removed by, for example, hydrolysis, leaving the
product of the reaction as a single enantiomer.
 The best chiral auxiliaries can be recycled, so although stoichiometric
quantities are
needed, there is no waste.

10. Flow chart of the chiral auxiliary strategy

11. Diel’s Alder reaction between cyclopentadiene benzyl acrylate
Chiral auxiliary : amide derived from valine via reaction to give asymmetric
product
An example

12. CHIRAL REAGENTS AND
CHIRAL CATALYSTS
Chiral reagent: enantio specific product
E.g. chiral boron hydride (CBS)
Corey, Bakshi, Shibitha

13. Enantio selective catalysts
 enantioselective catalysis are chiral coordination compounds
 Ligands show chirality
 Privileged ligands :(2,2'-bis(diphenylphosphino)-1,1'-
binaphthyl( BINAP),BINOL
R- BINAP S- BINAP

14. • ASYMMETRIC HYDROGENATION

15. ASYMMETRIC EPOXIDATION
ASYMMETRIC DIHYDROXYLATION

17. SEPARATION AND ANALYSIS OF ENANTIOMERS
same physicsl properties
 same NMR, IR, Retention factor,
retention time
Varying properties in the presence of
other chiral compounds
X-ray crystallography

18. conclusion
Drug safety
Pharmaceuticals
Flavours
Mimic nature

19. Clayden, Jonathan, Nick Greeves and Stuart Warren. Organic Chemistry, 2nd Edition. Oxford.
2012.
Finar, I. L. Organic Chemistry : Stereo Chemistry and Chemistry of Natural Products (vol:2),
5th Edition. Dorling Kindersley Pvt. Ltd. Noida, India. 1975.
Nasipuri, D. Stereochemistry of Organic Compounds: Principles and Applications, 2nd Edition.
New Age International Pvt. Ltd. New Delhi. 1994.
REFERENCES