Enantioselective synthesis of β-amino acids. Part 10: Preparation of novel α,α- and β,β-disubstituted β-amino acids from ( S)-asparagine

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 3CO 2H, CH 3OH, 100°C) affords enantiopure N-benzoylated β,β-disubstituted β-amino acid esters ( S)- 14– 16, with intact double bonds in the olefinic substituents.