Protecting group free synthesis of carboxyl-substituted dihydropyrimidines through Biginelli reaction
Chlorotrimethylsilane-promoted Biginelli-type reaction of benzaldehyde, acetoacetic acid derivatives, and various carboxyl-containing ureas was explored. It was found that the steric load of the urea substituents influenced strongly the reaction outcome; in particular, the method was efficient only in the case of unbranched mono-substituted ureas bearing either aliphatic or aromatic groups. The method allows performing a one-pot, protecting group free synthesis of dihydropyrimidines possessing carboxylic functionality.