Reaction of aspartic acid derivatives with Grignard reagents -: synthesis of γ,γ-disubstituted α- and β-amino-butyrolactones

A series of gamma,gamma -dimethyl and gamma,gamma -diphenyl substituted alpha- and beta -amino-butyrolactones have been prepared in enantiomerically pure form using L-aspartic acid as a chiral building block. For the final Grignard reaction the difference in chemical reactivity between the carboxyl groups of aspartic acid was increased or inverted by preparing the corresponding semiesters, diesters and anhydrides. The resulting hydroxyacids and hydroxyesters lactonised in most cases during work up. Thus, (2S)-2-ethoxycarbonyl-amino-succinic acid-4-methylester 1 re acted with methylmagnesium iodide to form (3S)-3-ethoxycarbonylamino-5,5-dimethyl-tetrahydrofuran-2-one 2b. Two interesting side products were obtained and were found to result from attack at the C-l carboxylic acid rather than the C-4 carboxylic ester group leading to (3S)-3-ethoxycarbonylamino-4-oxo-pentanoic acid methylester 3 and (4S)-4-ethoxycarbonylamino-5,5-dimethyl-tetrahydrofuran-2-one 5a. (C) 2000 Elsevier Science Ltd. All rights reserved.