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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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), Cs2 CO3 (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 2 Cl2 -MeOH
as eluent to provide the desired product.
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