E. Juaristi, M. Balderas, Heraclio López-Ruiz, V.M. Jiménez-Pérez, M. L. Kaiser-Carril y Y. Ramírez-Quirós. Enantioselective Synthesis of b-amino acids. Part 10: Preparation of novel a,a-and b,b-disubstituted b-amino acids from (S)-asparagine. Tetrahedron: Asymmetry, 10, 3493-3505 (1999). DOI: http://dx.doi.org/10.1016/S0957-4166(99)00328-6
Perhydropyrimidinone (S)-1 is alkylated with very high diastereoselectivity to give trans products (2S,5R)-3, (2S,5R)4 and (2S,5R)-5. Dialkylation of (S)-1 also proceeds with complete stereoselectivity to afford adducts (2S,5R)-6, (2S,5S)-6, (2S,5R)-7 and (2S,5S)-7. Hydrolysis (6N HCl, 100C) of monoalkylated derivative (2S,5R)-3 gives enantiopure ?-substituted ?-amino acid (R)-8. Hydrolysis of dialkylated adducts 6 and 7 affords enantiopure ?,?-disubstituted ?-amino acids (R)- or (S)-9 and (R)- or (S)-10. Related iminoester (2S,6S)-2 is alkylated with complete diastereoselectivity to give products (2S,6S)-1113 whose hydrolysis under relatively mild conditions (2N CF3CO2H, CH3OH, 100C) affords enantiopure N-benzoylated ?,?-disubstituted ?-amino acid esters (S)-1416, with intact double bonds in the olefinic substituents.