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,B-didehydroamino acid (DDAA) derivatives with 3,5-dihy dro-2H-1,4-oxazin-2-one structure 11a-f have been stereoselectively prepare d after condensation of chiral glycine equivalent 7 with aldehydes in the p resence of K2CO3 under mild solid-liquid phase-transfer catalysis reaction conditions. These new systems have been used in diastereoselective cyclopro panation reactions using Corey's ylide for the asymmetric synthesis of 1-am inocyclopropane-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-methylleuc ine. 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 end o selectivity for the synthesis of the enantiomerically pure bicyclic alpha -amino acids (-)-2-aminobicyclo[2.2.1]heptane-2-carboxylic and (-)-2-aminob icyclo[2.2.2]octane-2-carboxylic acids.