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Synthesis 2001(11): 1649-1658
DOI: 10.1055/s-2001-16762
PAPER
© Georg Thieme Verlag Stuttgart · New York

Siloxycyclopropanes in Ugi Four-Component Reaction: A New Method for the Synthesis of Highly Substituted Pyrrolidinone Derivatives

Reinhold Zimmera, Antje Ziemerb, Margit Grunerc, Irene Brüdgamd,, Hans Hartld,, Hans-Ulrich Reissig*a
a Institut für Chemie - Organische Chemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany
Fax: +49 (30)83855367; e-Mail: Hans.Reissig@chemie.fu-berlin.de;
b Institut für Polymerforschung Dresden e.V., Hohe Strasse 6, 01069 Dresden, Germany
c Institut für Organische Chemie, Technische Universität Dresden, 01062 Dresden, Germany
d Institut für Chemie - Anorganische und Analytische Chemie, Freie Universität Berlin, Fabeckstrasse 34-36, 14195 Berlin, Germany
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Publication History

Received 26 April 2001
Publication Date:
12 August 2004 (online)

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Abstract

Reaction of methyl trimethylsiloxycyclopropanecarboxylates 3 with amino acids, tert-butylisonitrile and methanol furnished amino diacid derivatives 2 as the result of an Ugi 5-center 4-component reaction. This one-pot reaction involves β-formyl esters such as 1 as intermediate, which are liberated in situ. Adducts 2 could be thermally cyclized to provide γ-lactams 4 in good yields. The multi component reaction was combined with this cyclization process to a fairly efficient one-pot procedure. Thus, cyclopropane derivative 3a was converted into γ-lactam 4a in good yield. Two of the γ-lactams 4 were reduced with lithium aluminum hydride to give pyrrolidine derivatives 5. Based on an X-ray analysis of the major diastereomer of compound 5d, the diastereoselectivity of the 4-component reaction is discussed.

Key words

amino acids - cyclopropanes - pyrrolidines - lactams - Ugi reaction

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1

X-ray analysis.

17

This type of Ugi reactions with ketones has been reported mainly with sterically less hindered isonitriles. [9] [10]

18

The configuration of the new stereogenic center of an (S)-proline derived adduct was S-configured according to an X-ray analysis, whereas the corresponding formula of this compound was drawn as R-configured at this carbon. [4]