References
Evans, P.A.; Qin, J.; Robinson, J.E.; Bazin, B. Angew. Chem., Int. Ed. Engl. 2007, 46, 7417-7419.
This mechanism was discussed thoroughly within this primary citation that was later cited by many papers including the three other ones shown below. This paper discusses the Biginelli reaction in detail. The Biginelli reaction proceeds through one of three primary bimolecular reaction products given lead to by the urea/aldehyde/acetoacetate systems. The first and limiting step of the reaction is an aldol condensation that eventually leads to carnebium ion, proposed to be the key intermediate in the reaction. This cation is then intercepted by urea leading to an intermediate ready for cyclization to dihydropyrimidine. A reliable approach is to use an unsaturated ketoester in the first step in the presence of sodium bicarbonate. This then proceeds through a Michael addition along with deprotection with HCl leading to the desired Bignelli compounds in high overall yield. A route leading to dihydropyrimidines having a hydrogen atom is the acid catalyzed condensation of urea with certain precursors.
Cousin #1: Cho, H.; Nishimura, Y. Tetrahedron Lett. 2014, 55, 411-414. This citation discusses the synthesis of dihydropyrimidines by condensation reactions.
Cousin #2: Kappe, O. C. Tetrahedron. 1993, 49, 6937-6963.
This citation uses the Biginelli condensation reaction to allow access to a large number of multifunctionalized dihydrophrimidines such as the one shown above.
Cousin #3: Cho, H.; Nishimura, Y.; Yasui, Y.; Yamaguchi, M. Tetrahedron Lett. 2012, 53, 1177-1179.
This citation also uses the Biginelli condensation to form a new compound, above.
Other references:
Biginelli, P. Gazz. Chim. Ital. 1893, 23, 360.
Sweet, F.; Fissekis, J. D. J. Am. Chem. Soc. 1973, 95, 8741.