Reactions of N-benzyl-pyridinium or -isoquinolinium ylides with ethyl 3-fluoro-3-(fluoroalkyl)acrylates to give fluoroalkyl-substituted indolizine and pyrrolo[2,1-a]isoquinoline derivatives

Abstract

In the presence of base, N-benzylpyridinium and N-benzylisoquinolinium ylides generated in situ from the N-benzyl-pyridinium or -isoquinolinium bromides react with ethyl 3-fluoro-3-fluoroalkyl(except bromodifluoromethyl)acrylates to give one or two fluoroalkylated indolizine and pyrrolo[2,1-a]isoquinoline derivatives through 1,3-dipolar cycloaddition followed by an oxidative aromatization or 1,3-H-shift aromatization process. While ethyl 3-bromodifluoromethyl-3-fluoroacrylate reacts with 4-nitrobenzylpyridinium ylide, a trifluoromethylated indolizine derivative was obtained unexpectedly. It is more remarkable that the reaction of ethyl 3-bromodifluoromethyl-3-fluoroacrylate with N-benzylisoquinolinium ylide produces a fluorocarbonyl-substituted pyrrolo[2,1-a]isoquinoline derivative, which is fully characterized by spectroscopic methods and X-ray diffraction analysis, in addition to the 1,3-H-shift aromatization product.