Prof. Corey introduced the chiral auxiliary (-)-8-phenylmenthol in 1978. He used it in his famous prostaglandin synthesis. Prof. Trost then introduced mandelic acid as a chiral auxiliary in 1980. In 1985, Prof. Whitesell introduced an alternative, (1R,2S)-trans-2-phenyl-1-cyclohexanol, since preparing menthol compounds is difficult. A chiral auxiliary is a temporary, optically active compound incorporated into a synthesis to control stereochemistry and selectively form one stereoisomer over the other. Important examples include Evans' oxazolidinones and their use in asymmetric alkylations.

1. Chiral auxiliary

3. Prof. E.J. Corey [Chemistry Nobel prize
winner-1990] in 1978 introduced Chiral
auxiliary…
with chiral 8-phenylmenthol.
(−)-8-Phenylmenthol

4. (−)-8-Phenylmenthol
He utilized this Chiral auxiliary in
his famous Prostaglandin synthesis…
Key Chiral Intermediate in
Prostaglandin synthesis
(−)-8-Phenylmenthol
Diastereoselective Diels-
Alder cycloaddition

5. Pheromone Synthesis using Chiral Auxiliary,
8-phenylmenthol

6. Prof. B.M. Trost in 1980 introduced
Mandelic acid as chiral auxiliary.

7. As preparation of menthol compound is
difficult, Prof. J. K. Whitesell in 1985
introduced an alternative trans-2-phenyl-
1-cyclohexanol.
(1R,2S)-trans-2-Phenyl-1-cyclohexanol
(1S,2R)-(+)-trans-2-Phenyl-1-cyclohexanol

8. What is Chiral Auxiliary!

9. A chiral auxiliary is a chemical
compound or unit…

10. that is temporarily incorporated
into an organic synthesis so that...

11. synthesis be carried out asymmetrically...

12. with the selective formation of
one of two stereo-isomers.
.
Schematic presentation

13. Substrate
[Achiral]
Chiral
Auxiliary
Chiral
Auxiliary
Substrate
[Achiral]
Chiral
Auxiliary
Reaction to form new
Chiral Compound
Chiral
Auxiliary
Product
[Chiral]
Product
Diastreo-selective
reaction
Step-1
Step-2
Recycling of Chiral Auxiliary

14. Chiral auxiliaries are optically
active compounds…

15. So, a chiral auxiliary is a…
stereogenic group or unit that is
temporarily incorporated into an organic
compound in order to control the
stereochemical outcome of the synthesis.

16. The chirality present in the auxiliary
can bias the stereoselectivity of one or
more subsequent reactions…

17. and introduce chirality in racemic
compounds or a pro-chiral center.
Pro-chiral center
Example

18. Prochiral
Substrate
Chiral
Auxiliary
Diastreoselective
Transformation
Chiral Auxiliary
Chiral Product
Recycling of
Chiral Auxiliary
Hydrolysis
Chiral Auxiliary will guide the preferential entry
of E leading to formation of excess of one Streo-
isomer over the other!

19. Prochiral
Substrate
H2N – Xca
Condensation
Diastreoselective
Reaction
H2N – Xca
Chiral Auxiliary
Chiral Auxiliary
Hydrolysis
Chiral Product
Recycling
Another one…

20. The regenerated Chiral auxiliary
can be reused/recycled.

21. Important Chiral Auxiliaries used
in Asymmetric Synthesis

22. One of the most utilized auxiliary in
asymmetric synthesis is chiral
oxazolidinones 1, pioneered by Prof. Evans.

23. The methodology of asymmetric
transformations developed with this
chiral imides has been most successful
in the stereoselective construction of…
 Numerous chiral building blocks.
 Natural products.
 Antibiotics and
 Medicinally important compounds.

24. Evans' Oxazolidinones
Alkylations - Example
Oxazolidinone
Because of enolate-geometry, one of its
two face is readily accessible for preferred
alkylation leading to the excess formation
of one stereoisomer over the other!
Metal chelation fixes
the conformation
Readily synthesized
from Amino acid
Preferred site of attack
– no steric hindrance!
Steric hindrance –
attacked is blocked!

25. Evans' Oxazolidinones Alkylations
Oxazolidinone
KOH
Diastreomer Enantiomer
 Enolate-chemistry- a very important
Strategy in Synthesis!
 One of the commonest means of forming
C–C bonds is via enolate-alkylation!
 If a chiral center present, it can get a
diastereoselective reaction.

26. With the great success of oxazolidininone 1,
many structural variants have been developed &
introduced in the armory of Chiral Auxiliaries of
Organic Chemistry as listed below:

27.  Cheap!
Criteria for Chiral Auxiliaries
 Easily attached!
 Induce stereochemistry!
 Chemically inert!
 Easily removed!
 Readily available!