ChemInform Abstract: Enantioselective Synthesis of β-Amino Acids. Part 10. Preparation of Novel α,α- and β,β-Disubstituted β-Amino Acids from (S)-Asparagine.

Abstract

Abstract Perhydropyrimidinone ( S )- 1 is alkylated with very high diastereoselectivity to give trans products (2 S ,5 R )- 3 , (2 S ,5 R )– 4 and (2 S ,5 R )- 5 . Dialkylation of ( S )- 1 also proceeds with complete stereoselectivity to afford adducts (2 S ,5 R )- 6 , (2 S ,5 S )- 6 , (2 S ,5 R )- 7 and (2 S ,5 S )- 7 . Hydrolysis (6N HCl, 100°C) of monoalkylated derivative (2 S ,5 R )- 3 gives enantiopure α-substituted β-amino acid ( R )- 8 . Hydrolysis of dialkylated adducts 6 and 7 affords enantiopure α,α-disubstituted β-amino acids ( R )- or ( S )- 9 and ( R )- or ( S )- 10 . Related iminoester (2 S ,6 S )- 2 is alkylated with complete diastereoselectivity to give products (2 S ,6 S )- 11 – 13 whose hydrolysis under relatively mild conditions (2N CF 3 CO 2 H, CH 3 OH, 100°C) affords enantiopure N -benzoylated β,β-disubstituted β-amino acid esters ( S )- 14 – 16 , with intact double bonds in the olefinic substituents.