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Synthesis 2011(10): 1587-1594  
DOI: 10.1055/s-0030-1260012
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Diversity-Oriented Silver(I)-Mediated Synthesis of Spiro-2-aminoimidazoles

Olga P. Pereshivkoa, Vsevolod A. Peshkova, Denis S. Ermolat’ev*a, Sofie Van Hovea, Kristof Van Heckeb, Luc Van Meerveltb, Erik V. Van der Eycken*a
a Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC), Department of Chemistry, Katholieke Universiteit Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
Fax: +32(16)327990; e-Mail: denis.ermolatev@chem.kuleuven.be; e-Mail: erik.vandereycken@chem.kuleuven.be;
b Biomolecular Architecture, Department of Chemistry, Katholieke Universiteit Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
Further Information

Publication History

Received 21 February 2011
Publication Date:
19 April 2011 (online)

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Abstract

A diversity-oriented protocol giving access to a novel class of spiro-cyclic guanidine derivatives is described. The copper(I)-catalyzed, three-component coupling of a ketone, an alkyne and a primary amine (KA²-coupling) provides the required secondary propargylamines and assures the generation of diversity. The key step of the protocol, a silver(I)-mediated tandem guanylation of secondary propargylamines followed by an intramolecular heterocyclization, provides the target bis-Boc-protected-2-iminoimidazolines spiro-fused with a five-, six- or seven-membered (heterocyclic) ring, which could, in most cases, be further deprotected to the spiro-2-aminoimidazoles.

Key words

2-aminoimidazoles - spiro compounds - tandem reaction - ring closure - silver

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26

Differences in R f values allow both minor and major products to be isolated through gradient-elution column chromatography.

27

See Supporting Information for details.

28

CCDC-801762 contains the supplementary crystallographic data for this paper and can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:+44(1223)336033; or deposit@ccdc.cam.ac.uk).