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Synlett 2010(17): 2611-2616  
DOI: 10.1055/s-0030-1258803
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Easy and Efficient Copper-Catalyzed Synthesis of Bicyclic Pyrimidinones under Mild Conditions

Qi Guoa, Haijun Yanga, Hongxia Liub, Yuyang Jiangb, Hua Fu*a
a Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
b Key Laboratory of Chemical Biology, Guangdong Province, College of Shenzhen, Tsinghua University, Shenzhen 518057, P. R. of China
Fax: +86(10)62781695; e-Mail: fuhua@mail.tsinghua.edu.cn;
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Publikationsverlauf

Received 22 July 2010
Publikationsdatum:
30. September 2010 (online)

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Abstract

A simple and efficient copper-catalyzed method has been developed for synthesis of bicyclic pyrimidinones containing six-, seven-, eight-membered rings under mild conditions. The protocol uses readily available 2-bromocycloalk-1-enecarboxylic acids, amidines, and guanidines as the starting materials, copper-catalyzed cascade couplings provide the corresponding bicyclic ­pyrimidinones without addition of any ligand or additive, and the method is of economical and practical advantages.

Key words

copper - cascade reaction - bicyclic pyrimidinone - nitrogen heterocycle - synthetic method

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2

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19

General Procedure for the Synthesis of Compounds 3a-s A two-neck round-bottom flask was charged with a magnetic stirrer, evacuated and backfilled with nitrogen. Amidine hydrochloride or guanidine hydrochloride 2a-f (0.6 mmol) or bis(guanidine)sulfate (2g, 0.35 mmol), CuI (0.05 mmol, 9.5 mg), Cs2CO3 (1 mmol, 326 mg), and DMF (1 mL) were added under nitrogen atmosphere. After a 15 min stirring, 2-bromocycloalk-1-enecarboxylic acid (1, 0.5 mmol) was added to the flask. The mixture was allowed to stir under nitrogen atmosphere at the shown temperature for some time (see Table  [²] ). After completion of the reaction, the mixture was concentrated with the aid of a rotary evaporator. The residue was purified by column chroma-tography on silica gel using PE-EtOAc or CH2Cl2-MeOH as eluent to provide the desired product.