Synthesis of 3-Fluoropyrroles

Significance

In the reported procedure 2-aryl-5-(bromomethyl)-1-pyrrolines were prepared in poor to good yields from benzonitriles and 3-butenylmagnesium bromide. The pyrrolines were subsequently α,α-difluorinated with Selectfluor in poor to excellent yields. Using only 1.2 equivalents of Selectfluor led to 95% conversion to the α-mono­fluorinated pyrroline. The difluorinated pyrrolines were aromatized to 5-alkoxymethyl- or 5-carboxaldehyde-pyrroles, the former in mediocre to ­excellent and the latter in very poor to mediocre yields. With the substrate R = MeO, the fluorination process gave an ˜1:1 mixture of the desired product and a product where the aryl ring is additionally fluorinated at the 3-position. These were not separable via column chromatography. The substrate scope was poorly studied, but one of the carboxaldehydes was further derivatized to show the utility of this process.