Asymmetric synthesis
- 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
- 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
- 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