Enantiospecific synthesis of norcoronamic acids

Article abstract of DOI:10.1016/S0957-4166(98)00245-6

The synthesis of enantiomerically pure norcoronamic acids, starting from enantiomerically pure 1,2-propanediols, is described.

Full text of DOI:10.1016/S0957-4166(98)00245-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 2233–2234
Enantiospecific synthesis of norcoronamic acids
Alain Hercouet,∗ Nicolas Godbert and Maurice Le Corre
Laboratoire de Synthèse Organique, Associé au CNRS. Université de Rennes I, Avenue du Général Leclerc,
35042 Rennes Cedex, France
Received 5 June 1998; accepted 16 June 1998
Abstract
The synthesis of enantiomerically pure norcoronamic acids, starting from enantiomerically pure 1,2-
propanediols, is described. © 1998 Elsevier Science Ltd. All rights reserved.
1-Aminocyclopropanecarboxylic acids (ACC derivatives) are currently attracting attention, because
of their conformationally constrained structure, providing them with particularly interesting biological
properties.1 In this area, allonorcoronamic and norcoronamic acids provide a significant challenge to
synthetic chemists, due to the difficulty in controlling the stereochemistry around the cyclopropane ring.
We have recently reported2 the synthesis of (−)-(1S,2R) allonorcoronamic acid 3, via condensation of
cyclic sulfate 2 on a Schiff base (Scheme 1).
Scheme 1.
Asymmetric syntheses of norcoronamic acids have also been reported,3–6 but several of these suffer
from unresolved mixtures and moderate diastereoisomeric excess. We now report a new and expedient
enantiospecific synthesis of optically active norcoronamic acid 4, one that can provide multigram
quantities of enantiomerically pure material (Scheme 2).
The synthesis of cyclic sulfate 2 from (S)-(+)-1,2-propanediol 1 was achieved in 95% overall yield by
the one pot procedure previously reported.2 The next step involved the condensation of 2 with dimethyl
∗
Corresponding author. Fax: (0) 0299286978; e-mail: Alain.Hercouet@univ-rennes1.fr
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00245-6

2234
A. Hercouet et al. / Tetrahedron: Asymmetry 9 (1998) 2233–2234
Scheme 2.
malonate in DME at room temperature in the presence of two equivalents of sodium hydride, to give
the alkylated diester 5 in nearly quantitative yield. In order to realize the aminoacid synthesis, selective
differentiation of the two carboxylate functions had to be done.
Regioselective saponification of racemic 5 to give the racemic monoacid ester 6 has been described
by Baldwin.7 In our hands, the same conditions applied to optically active diester 5 gave monoester 6
with 90% diastereoisomeric excess. To overcome this problem, we used a two step procedure. In the first
step, the diester was treated in methanol with one equivalent of sodium hydroxide. In the second step,
the brucine salt of the monoacid was recrystallized from ethanol. In these conditions the monoester 6
was obtained, after acidification, with 99.5% diastereoisomeric excess and 72% overall yield. Curtius
rearrangement of the cyclopropane carboxylic acid 6 and subsequent in situ reaction of the intermediate
isocyanate with benzyl alcohol, gave quantitatively the N-CBZ protected aminoacid ester 7.
Hydrolysis of carbamate 7 with 3 N HCl at reflux (12 h) led, after treatment with ion-exchange
resin (Dowex-50X8), to free (1R,2R)-1-amino-2-methylcyclopropane carboxylic acid 4 ((−)-(E)-
norcoronamic acid). The specific rotation of 4 is in agreement with the value previously reported.6 The
availability of both enantiomers of 1,2-propanediol allows the unambiguous preparation of either the
l or d forms of (E)-norcoronamic acid. The methodology described herein, complements the existing
approaches to this class of aminoacids.
References
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Jacquier, R. Bull. Soc. Chim. Fr. 1993, 130, 5–24. (c) Burgess, K.; Kwok-Kan, H.; Destradi, M. S. Synlett 1994, 575–583.
2. Hercouet, A.; Bessières, B.; Le Corre, M. Tetrahedron: Asymmetry 1996, 7, 283–284.
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