DIASTEREOSELECTIVE ALKYLATION OF (3S)-3-METHYLPIPERAZINE-2,5-DIONE AND (3R)-3-METHYLPIPERAZINE-2,5-DIONE DERIVATIVES - A CONVENIENT APPROACH TO BOTH (S)-ALANINE AND (R)-ALANINE

Treatment of (3S)-3-methylpiperazine-2,5-dione 6a with LHDMS followed by alkylation of the corresponding enolate with methyl iodide affords (3S,6S)-3,6-dimethyl derivative 7 in 98% de. The same reaction sequence carried out on (3R)-derivative 6b leads to a 93:7 diastereomeric mixture of (3R,6R)-8a and (3R,6S)-8b. Cleavage of the heterocyclic ring of 7 and ga with 57% HI leads to (S)- and (R)-alanine, respectively. The configuration at C-3 (of 6a and 6b) and at C-6 (of 7 and 8a) can be assigned on the basis of H-1 NMR spectroscopy and conformational analysis performed by MMPMI.