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A Direct Synthesis of Isocytosine Analogues by Carbonylative Coupling of α‐Chloro Ketones and Guanidines
Author(s) -
Capua Martina,
Perrone Serena,
Bona Fabio,
Salomone Antonio,
Troisi Luigino
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201601654
Subject(s) - chemistry , chemoselectivity , carbonylation , combinatorial chemistry , palladium , nucleobase , ring (chemistry) , organic chemistry , catalysis , carbon monoxide , dna , biochemistry
A valuable and direct method for the synthesis of 2‐aminopyrimidin‐4‐one derivatives is described. The strategy relies on the Pd‐catalysed carbonylation of α‐chloro ketones in the presence of mono‐ and disubstituted guanidines. Although the strategy also gave 2‐aminoimidazole derivatives as minor products, good chemoselectivity in favour of the six‐membered ring was achieved in all experiments. The in‐situ formation of a (β‐oxoacyl)palladium species has been invoked as the key step for the multicomponent process. Moreover, the method described could be of interest from a biological point of view, because it constitutes a straightforward strategy for the synthesis of structural analogues of the unnatural nucleobase isocytosine.