Asymmetric synthesis of (S)-α-methyl α-amino acids by alkylation of chiral 3,6-dihydro-2H-1,4-oxazin-2-ones using unactivated alkyl halides and organic bases

3,6-Dihydro-2H-1,4-oxazin-2-ones 1 have been diastereoselectively (>96% de) alkylated using unactivated alkyl halides and organic bases such as 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) at room temperature in the presence of LiI. Hydrolysis of the resulting alkylated systems afforded enantiomerically enriched (S)-alpha-methyl alpha-amino acids. When 1,3-diiodopropane was used, spontaneous N-alkylation also took place giving bicyclic oxazinone 6 which was hydrolyzed to (S)-alpha-methylproline. (C) 1998 Elsevier Science Ltd. All rights reserved.