Abstract
Dihydropyrimidines (DPs) show a wide range of biological activities suitable for medicinal
applications. Among DP derivatives, 2-aryl-DPs have been reported to display remarkable
pharmacological properties. In this work, a method of synthesizing hitherto unavailable
fully substituted pentasubstituted 2-aryl-DPs as tautomeric mixture is described using
a Pd(PPh3)4-catalyzed/CuBr-mediated 2-arylation reaction. The reaction using aryltributylstannanes
with various substituents such as MeO, Me, Ph, CF3, CO2Me, and NO2 groups efficiently afforded the corresponding 2-aryl-DPs in high yields. Heteroaryltributylstannanes
having 2-thienyl, 3-thienyl, or 2-pyridinyl groups were also suitable for the reaction.
Regarding the substituents at the 4-, 5-, and 6-positions of DPs, the reactions of
DPs bearing substituents such as Me, n-C3H7, n-C5H11, -(CH2)5-, phenyl, and fluorenylidene groups proceeded smoothly to give the desired products.
The synthetic method was also applied to a 2-thioxo-DP to give the 2-aryl-DP. Therefore,
the reaction will help expand DP-based molecular diversity, which may impact biological
and pharmacological studies.
Key words
dihydropyrimidine - fully substituted 2-aryldihydropyrimidine - Pd-catalyzed/Cu-mediated
reaction - Liebeskind–Srogl-type cross-coupling reaction - palladium catalyst - copper
reagent - aryltributylstannanes - heteroaryltributylstannanes
