TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 11 (2000) 3827–3836 Pergamon Reaction of aspartic acid derivatives with Grignard reagents—synthesis of ,-disubstituted - and -amino-butyrolactones Thomas Brinkmann, Alfred Gilg, Andreas Hamm, Hendrik Lu ¨ sch, Guido Morbach and Horst C. Uzar* Institut fu ¨r Organische Chemie, Universita ¨t–Gesamthochschule Siegen, Adolf -Reichwein -Straße, D-57068 Siegen, Germany Received 8 August 2000; accepted 29 August 2000 Abstract A series of ,-dimethyl and ,-diphenyl substituted - and -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 reacted with methylmagnesium iodide to form (3S )-3-ethoxycarbonyl- amino-5,5-dimethyl-tetrahydrofuran-2-one 2b. Two interesting side products were obtained and were found to result from attack at the C-1 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. © 2000 Elsevier Science Ltd. All rights reserved. 1. Introduction Non-proteinogenic -amino acids are interesting target molecules in their own right due to the biological and toxicological properties displayed by many of these compounds. 1,2 Furthermore, they are often used as chiral starting materials for the synthesis of natural products and chiral auxiliaries. 3 For example, L-homoserine lactone can be synthesised from L--amino acids, 4 but the synthesis of substituted L-homoserine lactones, which are -amino--butyrolactones, has only been rarely explored. A potential preparation starts from the inexpensive L-aspartic acid. The tert -alcohol function can be introduced by addition of a Grignard reagent. However, one has to direct the reaction to the 4- rather than to the 1-carboxyl group, which can be achieved * Corresponding author. Tel: +49-271-740-4244; fax: +49-271-740-2780; e-mail: uzar@chemie.uni-siegen.de 0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII:S0957-4166(00)00344-X