Synthesis of 6-Fluorinated 3,4-Dihydro-pyrimidinones

Significance

Reported is the reaction of ethyl 3-butenoate 1 with fluorinated cyanides 2 to form products 3 which upon condensation with iso(thio)cyanates 5 lead to fluorinated 3,4-dihydropyrimidinones 6 via a terminal intramolecular aza-Michael reaction. The formation of the thermodynamic products 3 was achieved by slow addition of the fluorinated cyanides 2 to the lithium enolate of 1 (fast addition leads to the kinetic products 4). The yields of 3 are modest due to their instability during purification. The 6-fluorinated pyrimidinones 6 were thus obtained in low to moderate yields, with better yields being achieved in case of isothiocyanates.