One pot synthesis of novel α,β-dichloro-β-trifluoromethylated enones and their application to the synthesis of trifluoromethylated heterocycles

Trifluoropropynyllithium was reacted with 1 equiv of Weinreb benzamides in THF at −78 to 0 °C, followed by treatment with 4 equiv of trifluoromethanesulfonyl chloride to give α,β-dichloro-β-trifluoromethylated enones 1 in 61–68% yield. The reactions of 1a with substituted amidines or hydrazines in refluxing 1,4-dioxane-CH3CN afforded trifluoromethylated chloropyrimidines 3 and chloropyrazoles 6 in 58–98% yields. The microwave-assisted coupling reactions of 3 with substituted phenylstannane and allylstannane in refluxing CH3CN in the presence of Pd(PPh3)4 provided the corresponding phenyl and allyl substituted pyrimidines 4 in 89–98% yields.

Graphical abstractTrifluoropropynyllithium was reacted with 1 equiv of Weinreb benzamides in THF at −78 to 0 °C, followed by treatment with 4 equiv of trifluoromethanesulfonyl chloride to give α,β-dichloro-β-trifluoromethylated enones 1 in 61–68% yield. The reactions of 1a with substituted amidines or hydrazines in refluxing 1,4-dioxane-CH3CN afforded trifluoromethylated chloropyrimidines 3 and chloropyrazoles 6 in 58–98% yields. The microwave-assisted coupling reactions of 3 with substituted phenylstannane and allylstannane in refluxing CH3CN in the presence of Pd(PPh3)4 provided the corresponding phenyl and allyl substituted pyrimidines 4 in 89–98% yields. Figure optionsDownload full-size imageDownload as PowerPoint slide