Cu catalyzed [4 + 2] cycloaddition for the synthesis of highly substituted 3-fluoropyridines

A copper catalyzed annulation-aromatization of benzyl trifluoromethyl ketimines with 3-acryloyloxazolidin-2-ones for the synthesis of 3-fluoropyridines through double C-F bond cleavages has been developed. In this approach, the annulation occurred between the in situ formed dienes from trifluoromethyl ketimines via the first C-F bond cleavage and 3-acryloyloxazolidin-2-ones. Then the aromatization afforded 3-fluoropyridines in moderate yields through the second C-F bond cleavage. The 3-fluoropyridine products could be further hydrolyzed to multi-substituted 3-pyridinecarboxylic acids. A copper catalyzed [4 + 2]annulation-aromatization of benzyl trifluoromethyl ketimines with 3-acryloyloxazolidin-2-ones has been developed for the synthesis of 3-fluoropyridines in moderate yields through double C-F bond cleavages.