Highly Enantioselective Synthesis of the 6-isopropyl-3,4-dihydropyrimidin-2-(1H)-thiones via Asymmetric Catalytic Biginelli Reactions

Author(s): Zhijun Hang , Guoyong Dai , Han Yu , Sheng Han .

Journal Name: Current Organic Chemistry

Volume 20 , Issue 27 , 2016

Become EABM
Become Reviewer

Graphical Abstract:


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.

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 27
Year: 2016
Page: [2917 - 2925]
Pages: 9
DOI: 10.2174/1385272820666160411151148
Price: $58

Article Metrics

PDF: 31
HTML: 4
EPUB: 1
PRC: 1