Synthesis 2005(2): 296-300  
DOI: 10.1055/s-2004-834927
PAPER
© Georg Thieme Verlag Stuttgart · New York

Improved Synthesis of γ-Nitro-α-Amino Ester and Acid Derivatives

Roberto Ballini*a, Cesare Balsaminib, Francesca Bartoccinib, Massimo Gianottib, Chiara Martinelli b, Nicoletta Savoretti
a Dipartimento di Scienze Chimiche dell’Università, Via S. Agostino 1, 62032 Camerino (MC), Italy
b Istituto di Chimica Farmaceutica, Università degli Studi di Urbino ‘Carlo Bo’, Piazza Rinascimento 6, 61029 Urbino (PU), Italy
Fax: +39(0737)402297; e-Mail: roberto.ballini@unicam.it;
Further Information

Publication History

Received 27 August 2004
Publication Date:
24 November 2004 (online)

Abstract

A useful microwave-assisted synthesis of γ-nitro-α-amino esters and corresponding acids, under mild conditions and without solvent, is described. The desired products were obtained via Michael addition from methyl N-(diphenylmethylene)-2,3-didehydroalaninate and commercially available nitroalkanes.

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The nitroalkyl additions to 1 can be alternatively run in the classic way: i.e. in THF at r.t. With little change in the stoichiometry (substrate/nitroalkane ratio = 1:1.5), but with much longer reaction times (3-5 h), we obtained the adducts in yields close to those from microwave-induced reactions.

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The stereochemistry depicted in Scheme [2] was assigned on the base of 1H NMR measurements, as follows. In the decoupled spectrum the H-2 proton shows two coupling constants (J 2,3a = 10.4 Hz and J 2,3b = 4.9 Hz) consistent with a pseudo-axial conformation. A coupling between H-3a and H-4 (J 3a,4 = 6.1 Hz) and the absence of coupling between H-3b and H-4 are suitable for a structure, where the H-4 proton was eclipsed with H-3a, and where H-4 had a dihedral angle of about 90° with H-3b. This hypothesis is furthermore supported by NOE values that are higher between H-4 and H-3a than between H-4 and H-3b. Finally, no NOE was observed between H-4 and H-2, a finding in accord to the given structure.