Enantiomerically pure cis-and trans-5-alkyl-l-benzoyl-2-(tert-butyl)-~~-methylimidazolidin-4-ones (1, 2, 11, 15, 16) and trans-2-(terf-butyl)-3-methyl-5-phenylimidazolidin-4-one (20). readily available from (S)-alanine, (S)-valine, (S)-methionine, and (R)-phenylglycine are deprotonated to chiral enolates (cf. 3, 4, 12, 21). Diastereoselective alkylation of these enolates to 5,5-dialkyl-or 5-alkyl-5-arylimidazolidinones (5, 6, 9, 10, 13a-d, 17, 18, 22) and hydrolysis give a-alkyl-a-amino acids such as (R)and (S)-a-methyldopa (7 and 8a, resp.), (S)-amethylvaline (14) and (R)-a-methyl-methionine (19). The configuration of the products is proved by chemical correlation and by NOE 'H-NMR measurements (see 23, 24). In the overall process, a simple, enantiomerically pure a-amino acid can be a-alkylated with retention or with inversion of configuration through pivalaldehyde acetal derivatives. Since no chiral auxiliary is required, the process is coined 'self-reproduction of a center of chirality'. The method is compared with other a-alkylations of amino acids occurring without racemization. The importance of enantiomerically pure, a-branched a-amino acids as synthetic intermediates and for the preparation of bio~ogicdl~y active compounds is discussed.In [l], we have shown that simple amino acids such as (S)-alanine, (S)-valine, (R)-phenylglycine, (S)-phenylalanine, and (S)-methionine can be converted selectively to imidazolidinones such as 1 and 2 of either cis-or trans-configuration. We now show that these imidazolidinones are deprotonated to synthetically useful chiral enolates.A) Reactions of the Chiral Imidazolidinone Enolates with Electrophiles. -As a first example, the preparation of ( R ) -or (S)-a -methyldopa ( =I 2-amino-2-methyl-3-(3,4-di-hydroxypheny1)propionic acid) from (S)-alanine is described (Scheme I). Solutions of the imidazolidinones (1 or 2) in THF were treated at dry-ice temperature with a slight excess of lithium diisopropylamide (LDA). Bright orange-red-colored solutions of the enantiomeric enolates (3, 4) were formed, which were combined with 3,4-dimethoxybenzyl bromide. Rapid decolorization indicated the progress of the alkylation step furnishing the enantiomeric 5,5-disubstituted imidazolidinones (5, 6, ca. 60 YO). We did not detect more than one diastereoisomer by HPLC of the crude products. Within experimental error, the two isomers 5 and 6 had identical physical properties such as melting points, IR, and NMR spectra, but an opposite sense of specific rotation.The heterocyclic ring and the phenolic methyl-ether groups of the enantiomer 6 were cleaved by heating for 4 hours in 6~ HC1 at 180" in a sealed tube. Isolation of the a-methyldopa thus produced caused considerable problems due to the known [2a] sen-')
2,Part of the projected Ph. D. theses of J.
