New chiral didehydroamino acid derivatives from a cyclic glycine template with 3,6-dihydro-2H-1,4-oxazin-2-one structure: applications to the asymmetric synthesis of nonproteinogenic alpha-amino acids.
New chiral (Z)-alpha,beta-didehydroamino acid (DDAA) derivatives with 3,5-dihydro-2H-1,4-oxazin-2-one structure 11a-f have been stereoselectively prepared after condensation of chiral glycine equivalent 7 with aldehydes in the presence of K(2)CO(3) under mild solid-liquid phase-transfer catalysis reaction conditions. These new systems have been used in diastereoselective cyclopropanation reactions using Corey's ylide for the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids (ACCs) such as allo-corononamic and allo-norcoronamic acids. The hydrogenation reaction of these systems at ambient pressure in the presence of formaldehyde affords saturated oxazinones and N-methylated oxazinones which have been transformed into the N-methyl-alpha-amino acids (N-MAAs) (S)-2-(methylamino)butanoic acid and (S)-N-methylleucine. In addition, the parent alpha, beta-didehydroalanine derivative 11g has been prepared by a direct aminomethylation-elimination sequence from 7 and Eschenmoser's salt and has been used in Diels-Alder cycloaddition with endo selectivity for the synthesis of the enantiomerically pure bicyclic alpha-amino acids (-)-2-aminobicyclo[2.2.1]heptane-2-carboxylic and (-)-2-aminobicyclo[2.2.2]octane-2-carboxylic acids.
Chinchilla
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R
Departamento de Química Orgánica, Universidad de Alicante, Apartado 99, 03080 Alicante, Spain.
Falvello
L R
LR
Galindo
N
N
Nájera
C
C
D000596:Amino Acids / Q000138:chemical synthesis*; D002384:Catalysis; D005998:Glycine / Q000737:chemistry*; D007202:Indicators and Reagents; D010078:Oxazines / Q000138:chemical synthesis*; D010165:Palladium; D013237:Stereoisomerism; D014961:X-Ray Diffraction
D000596:Amino Acids; D007202:Indicators and Reagents; D010078:Oxazines; D010165:Palladium; D005998:Glycine