Asymmetric Synthesis Employing a Chiral 5-Methoxy-1,4-oxazin-2-one Derivative: Preparation of Enantiomerically Pure α-Quaternary α-Amino Acids
✍ Scribed by Oliver Achatz; Andrea Grandl; Klaus Theodor Wanner
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 423 KB
- Volume
- 1999
- Category
- Article
- ISSN
- 1434-193X
No coin nor oath required. For personal study only.
✦ Synopsis
A new asymmetric synthesis of disubstituted α-amino acids
From the major diastereomers 17c-d the corresponding αamino acids 19c-d are obtained enantiomerically pure upon is presented. This synthesis is based on the chiral 5-methoxy-1,4-oxazin-2-one derivative 5 relying on the α-hydroxy acid hydrolytic cleavage with aqueous sodium hydroxide. Alkylation of the enolate ion of 5 with epichlorohydrines as 1 as a chiral auxiliary. Alkylation reactions of the glycine equivalent 5 are performed by deprotonation with sec-bifunctional electrophiles provides the cyclopropyl derivatives 20a-b. Direct hydrolysis or oxidation of 20a-b, butyllithium and subsequent reaction with alkyl halides, yielding the monoalkylated compounds 13 and 14. A second followed by reductive amination and hydrolysis leads to the substituted 1-aminocyclopropanecarboxylic acids 21a-b and alkylation step of the lithium enolates of 13 and 14 leads to the α,α-disubstituted compounds 17. Both steps proceed with 24a-b. good yields and excellent stereoselectivities (up to 99% de).