191284-36-3Relevant academic research and scientific papers
Asymmetric synthesis of α-methyl α-amino acids by diastereoselective alkylation of optically active 6-isopropyl-3-methyl-2,3-dihydro-6H-1,4-oxazin-2-ones
Chinchilla,Falvello,Galindo,Najera
, p. 995 - 997 (1997)
At room temperature already highly diastereoselective alkylation of the new, cyclic, chiral alanine ester derivatives (6R)-1 can be achieved with either K2CO3 as base under solid liquid phase-transfer catalysis or Pd catalysis under neutral conditions. The products (3S,6R)-2 can be easily hydrolyzed to form (S)-α-methyl α-amino acids.
Chiral 3,6-dihydro-2H-1,4-oxazin-2-ones as alanine equivalents for the asymmetric synthesis of α-methyl α-amino acids (AMAAs) under mild reaction conditions
Chinchilla, Rafael,Galindo, Nuria,Nájera, Carmen
, p. 704 - 717 (2007/10/03)
3,6-Dihydro-2H-1,4-oxazin-2-ones 1 act as very reactive chiral cyclic alanine equivalents and can be diastereoselectively alkylated or allylated using mild reaction conditions: potassium carbonate under phase-transfer catalysis (PTC) conditions when using activated alkyl halides, organic bases such as tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2- diazaphosphorine (BEMP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) when using unactivated alkyl halides, and neutral Pd(0)-catalysis when allylic carbonates are used. In most cases, the diastereoselectivity under all these different reaction conditions is excellent although the reactions are always carried out at room temperature. Hydrolysis of the obtained alkylated or allylated oxazinones allows the preparation of enantiomerically enriched (S)- α-methyl α-amino acids (S)-AMAAs. The PTC and organic base methodologies have also been applied to the synthesis of (R)-α-methyl α-amino acids starting from (R)-alanine. When dihalides are used as electrophiles under PTC or BEMP conditions, a spontaneous N-alkylation also takes place giving bicyclic oxazinones, which can be hydrolyzed to enantiomerically pure cyclic (S)-AMAAs.
