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Chiral auxiliary!

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Dipakchandra Sarkar
Dipakchandra Sarkar

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.

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Chiral auxiliary
Chiral auxiliary!
Prof. E.J. Corey [Chemistry Nobel prize winner-1990] in 1978 introduced Chiral auxiliary… with chiral 8-phenylmenthol. (−)-8-Phenylmenthol
(−)-8-Phenylmenthol He utilized this Chiral auxiliary in his famous Prostaglandin synthesis… Key Chiral Intermediate in Prostaglandin synthesis (−)-8-Phenylmenthol Diastereoselective Diels- Alder cycloaddition
Pheromone Synthesis using Chiral Auxiliary, 8-phenylmenthol
Prof. B.M. Trost in 1980 introduced Mandelic acid as chiral auxiliary.
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
What is Chiral Auxiliary!
A chiral auxiliary is a chemical compound or unit…
that is temporarily incorporated into an organic synthesis so that...
synthesis be carried out asymmetrically...
with the selective formation of one of two stereo-isomers. . Schematic presentation
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
Chiral auxiliaries are optically active compounds…
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.
The chirality present in the auxiliary can bias the stereoselectivity of one or more subsequent reactions…
and introduce chirality in racemic compounds or a pro-chiral center. Pro-chiral center Example
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!
Prochiral Substrate H2N – Xca Condensation Diastreoselective Reaction H2N – Xca Chiral Auxiliary Chiral Auxiliary Hydrolysis Chiral Product Recycling Another one…
The regenerated Chiral auxiliary can be reused/recycled.
Important Chiral Auxiliaries used in Asymmetric Synthesis
One of the most utilized auxiliary in asymmetric synthesis is chiral oxazolidinones 1, pioneered by Prof. Evans.
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.
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!
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.
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:
 Cheap! Criteria for Chiral Auxiliaries  Easily attached!  Induce stereochemistry!  Chemically inert!  Easily removed!  Readily available!

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Chiral auxiliary!