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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… Diastereoselective Diels- Alder cycloaddition Key Chiral Intermediate in Prostaglandin synthesis (−)-8-Phenylmenthol 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 Recycling of Chiral Auxiliary Substrate Chiral [Achiral] Auxiliary Chiral Step-1 Reaction to form new Auxiliary Chiral Compound Chiral Substrate Auxiliary [Achiral] Product [Chiral] Diastreo-selective Step-2 reaction Chiral Product 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 Diastreoselective Transformation Prochiral Chiral Substrate Auxiliary Recycling of Hydrolysis Chiral Auxiliary Chiral Auxiliary Chiral Product Chiral Auxiliary will guide the preferential entry of E leading to formation of excess of one Streo- isomer over the other! Another one… Condensation H2N – Xca Prochiral Chiral Auxiliary Substrate Diastreoselective Reaction Recycling Hydrolysis H2N – Xca Chiral Product Chiral Auxiliary 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 Preferred site of attack – no steric hindrance! Metal chelation fixes the conformation Readily synthesized from Amino acid Oxazolidinone Steric hindrance – attacked is blocked! 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! Evans' Oxazolidinones Alkylations KOH Oxazolidinone 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: Criteria for Chiral Auxiliaries Cheap! Readily available! Easily attached! Induce stereochemistry! Chemically inert! Easily removed!.
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