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A new and practical method for the asymmetric synthesis of γ-amino acids from β,γ-butenolides by an in situ esterification, condensation, and reduction in a one-pot procedure is described. This method is quite general for the preparation of both enantiomers of aryl or aliphatic γ-amino acids in high yields. These γ-amino-acid derivatives were also shown to be versatile synthetic intermediates for further transformations by their conversion to γ-lactams, δ-amino alcohols, and hydrolysis products in high yields with no racemization.

We describe highly enantioselective synthesis of beta-amino acid derivatives (1a-c) using asymmetric hydrogenation of alpha-aminomethylacrylates (2a-c), which contain a free basic N H group, as the key step. The alpha-aminomethylacrylates (2a-c) were prepared using the Baylis-Hillman reaction of an appropriate aldehyde with methyl acrylate followed by acetylation of the resulting allylic alcohols (4a-b) and S(N)2'-type amination of the allylic acetates (3a-b).

[reaction: see text] An efficient and practical N-methylation of amino acid derivatives with dimethyl sulfate in the presence of sodium hydride and a catalytic amount of water is described. Reaction of water with sodium hydride generated highly reactive dry sodium hydroxide, which led to much faster reaction rates than powdered sodium hydroxide itself.

Enantioselective syntheses of (R)-and (S)-2-N-carbomethoxy-5-aminoindanes from (R)- and (S)-phenylalanines, respectively, are described. A Friedel-Crafts reaction employing N-carbomethoxy phenylalanine leads to chiral 2-N-carbomethoxy-1-indanone, which is diastereoselectively reduced to 1-hydroxy-2-N-carbomethoxyindane. After protection of the hydroxyl group, a regioselective nitration gives a 6-nitroindane intermediate, which upon hydrogenation affords (R)-or (S)-2-N-carbomethoxy-5-aminoindane. [ABSTRACT FROM AUTHOR]