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Synlett 2004(10): 1817-1819  
DOI: 10.1055/s-2004-829561
LETTER
© Georg Thieme Verlag Stuttgart · New York

Methods for the Construction of New Highly Functionalised Guanidines

Eric Wellner, Helena Sandin*, Marie-Louise Swanstein
Active Biotech AB, Department of Drug Discovery, Box 724, 22007 Lund, Sweden
Fax: +46(46)191246; e-Mail: helena.sandin@activebiotech.com;
Further Information

Publication History

Received 30 April 2004
Publication Date:
15 July 2004 (online)

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Abstract

In this study, we present a fast and chemoselective protocol to highly functionalised guanidines. Guanidines containing a hydroxy function were constructed in the microwave by regioselective ring opening of epoxides in the presence of ammonium hydroxide giving the primary amines, which then were reacted with isothiouronium salts. Direct coupling of an unsubstituted guanidine with an epoxide in the presence of n-BuLi gave the same product.

Key words

amino alcohols - epoxides - chemoselectivity - regio­selectivity - ring opening

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7

Using protected building blocks (path B), the reaction performed less sluggishly leading to a substantially increase in yield.

10

NMR spectroscopy indicates also the formation of a by-product with unsymmetrical ring substitution. Attempts to isolate this compound failed.

11

The addition of Wang resin ensures the removal of the unreacted isothiouronium salt. This underlines the ambivalent reactivity of the starting material 5 towards alcohols3 and amines under microwave conditions.