Greatly simplified procedures for the synthesis of α-amino acids by the direct alkylation of pseudoephedrine glycinamide hydrate

Article abstract of DOI:10.1021/jo990341z

A modified procedure for the synthesis of highly enantiomerically enriched α-amino acids is described that involves the direct alkylation of pseudoephedrine glycinamide hydrate (1 · H₂O) followed by hydrolysis. The modified procedure was developed to overcome several inconvenient aspects of our earlier reported procedure. Advantages of the new method include (1) a greatly simplified one-step synthesis of the alkylation substrate (1 · H₂O) by the direct combination of glycine methyl ester hydrochloride with pseudoephedrine in the presence of lithium tert-butoxide, (2) the use of the weaker base lithium hexamethyldisilazide (LHMDS) in lieu of lithium diisopropylamide (LDA) for the enolization reaction, (3) a protocol for the direct alkylation of 1 · H₂O without the need for prior drying of the alkylation substrate, and (4) a one-step alkylation procedure that generates LHMDS and anhydrous lithium chloride simultaneously from the reaction of lithium metal with n-hexyl chloride in the presence of hexamethyldisilazane.