K. Ohara et al. / Tetrahedron Letters 50 (2009) 1463–1465
1465
diisopropylamine was guanylated in 75% yield, which compared
References and notes
favorably with all the other methods reported in the literature
(entry 2).4,8,11
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Although the precise reaction mechanism has not been clarified
yet, we assume that a carbodiimide is the key intermediate, which
is trapped by the amine affording the expected protected guanidine
along with triethylamine iodide and succinimide derivatives.20
In conclusion, we demonstrated the ability of the thiophilic NIS
to promote the conversion of amines into protected guanidines.
This reaction was shown to easily tolerate a diversity of substitu-
tion patterns on the amines. Thioureas and S-methylisothioureas
are common reagents for the synthesis of guanidines, and this con-
version requires usually initial activation by heavy metal or the use
of Mukaiyama’s reagent. Guanylation with NIS eliminates without
perceptible loss of yield the use of toxic heavy metals and the prob-
lem associated with their elimination. Moreover, it is an attractive
alternative to Mukaiyama’s reagent, especially when solubility and
purification issues are encountered.
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Acknowledgments
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We gratefully acknowledge l’Université de Montpellier 2 for
financial support. K.O. thanks ‘l’Association pour la Recherche sur
le Cancer’ (ARC) for a doctoral fellowship.
Supplementary data
19. (a) Ley, K.; Eholzer, U. Angew. Chem., Int. Ed. 1966, 5, 674; (b) Ottmann, G.;
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Supplementary data associated with this article can be found, in