Chemoselective Synthesis of 6-Polyfluoroalkyl-4-styrylpyrimidines via Pinner-type Condensation of 1-Polyfluoroalkyl-3-styryl-1,3-diketones with 1,3-N,N-Dinucleophiles

Abstract Simple and convenient chemoselective methods for the synthesis of 4-styryl-6-polyfluoroalkylpyrimidines based on the Pinner-type condensation of 1-polyfluoroalkyl-3-styryl-1,3-diketones with S-alkylisothiourea, guanidines, and amidines have been developed. The cyclocondensation of 1-polyfluoroalkyl-3-styryl-1,3-diketones with S-alkylisothiourea salts in an EtOH/AcOH (2:1) solution in the presence of NaOAc under reflux for 8–12 h leads to 2-alkylsulfanyl-4-styryl-6-polyfluoroalkylpyrimidines in 56–89% yields. A similar reaction involving these enediones with guanidine or amidine salts in the presence of B(OMe)3 in MeCN under reflux for 1–5 h affords the corresponding 4-styryl-6-polyfluoroalkylpyrimidines in 57–96% yields. The high reactivity of the 1,3-dicarbonyl fragment of 1-polyfluoroalkyl-3-styryl-1,3-diketones toward 1,3-N,N-dinucleophiles is due to charge control of the reaction, which is in good agreement with the DFT calculation data.