244233-40-7Relevant academic research and scientific papers
Asymmetric synthesis employing a chiral 5-methoxy-1,4-oxazin-2-one derivative: Preparation of enantiomerically pure α-quaternary α-amino acids
Achatz, Oliver,Grandl, Andrea,Wanner, Klaus Theodor
, p. 1967 - 1978 (2007/10/03)
A new asymmetric synthesis of disubstituted α-amino acids is presented. This synthesis is based on the chiral 5-methoxy-1,4-oxazin-2-one derivative 5 relying on the α-hydroxy acid 1 as a chiral auxiliary. Alkylation reactions of the glycine equivalent 5 are performed by deprotonation with secbutyllithium and subsequent reaction with alkyl halides, yielding the monoalkylated compounds 13 and 14. A second alkylation step of the lithium enolates of 13 and 14 leads to the α,α-disubstituted compounds 17. Both steps proceed with good yields and excellent stereoselectivities (up to 99% de). From the major diastereomers 17c-d the corresponding α-amino acids 19c- d are obtained enantiomerically pure upon hydrolytic cleavage with aqueous sodium hydroxide. Alkylation of the enolate ion of 5 with epichlorohydrines as bifunctional electrophiles provides the cyclopropyl derivatives 20a-b. Direct hydrolysis or oxidation of 20a-b, followed by reductive amination and hydrolysis leads to the substituted 1-aminocyclopropanecarboxylic acids 21a- b and 24a-b.
