Abstract
In 1893, the synthesis of 3,4-dihydropyrimidin-2(1H)-ones via three-component condensation reaction of an aromatic aldehyde, urea and ethyl acetoacetate was reported for the first time by P. Biginelli. In the past century, such 3,4-dihydropyrimidin-2-(1H)-ones and related heterocyclic compounds have received a considerable amount of attention due to the interesting pharmacological properties associated with this heterocyclic scaffold. In particular, in recent twenty years, the synthesis of functionalized 3,4-dihydropyrimidin-2(1H)-ones have made great breakthrough. However, the asymmetric synthesis of functionalized 3,4-dihydropyrimidin-2(1H)-ones catalyzed by organocatalysts also is less. Furthermore, the 6-isopropyl dihydropyrimidines are very important intermediates for Statin drug. In this article, we mainly developed a simple and practical scheme for the synthesis of 6-isopropyl-3,4-dihydropyrimidines in a one-pot three-component condensation of aldehydes, β-dicarbonyl compounds, and thiourea via organocatalyzed asymmetric Biginelli reaction. Under the optimal reaction conditions, a series of desired products with remarkable pharmacological interest was obtained in high yields with excellent enantiomeric excess (up to 99% ee) using this practical method.
Keywords: Biginelli reaction, asymmetric organocatalysis, chiral BINOL-derived phosphoric acid, 6-isopropyl-3, 4-dihydropyrimidines.
Graphical Abstract
Call for Papers in Thematic Issues
Catalytic C-H bond activation as a tool for functionalization of heterocycles
The major topic is the functionalization of heterocycles through catalyzed C-H bond activation. The strategies based on C-H activation not only provide straightforward formation of C-C or C-X bonds but, more importantly, allow for the avoidance of pre-functionalization of one or two of the cross-coupling partners. The beneficial impact of ...read more
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