Substituent-Driven Selective -/-Alkylation of 4-(Trihalomethyl)pyrimidin-2(1)-ones Using Brominated Enones.

The selective - or -alkylation of 4-(trihalomethyl)pyrimidin-2(1)-ones, using 5-bromo enones/enaminones as alkylating agents, is reported. It was found that the selectivity toward the - or -regioisomer is driven by the substituent present at the 6-position of the pyrimidine ring, thus enabling the preparation of each isomer as the sole product, in 60-95% yields. Subsequent cyclocondensation of the enaminone moiety with nitrogen dinucleophiles led to pyrimidine-azole conjugates in 55-83% yields.