Visible-Light-Induced Decarboxylative Acylation of Pyridine N-Oxides with α-Oxocarboxylic Acids Using Fluorescein Dimethylammonium as a Photocatalyst

Herein, the development of a visible-light-induced catalytic system to achieve the decarboxylative acylation of pyridine N-oxides with alpha-oxocarboxylic acids, at room temperature and using the organic dye fluorescein dimethylammonium as a new type of photocatalyst, is reported. A series of 2-arylacylpyridine N-oxides were selectively synthesized in moderate to good yields by controlling the polarity of the reaction solvent. The developed strategy was successfully applied in the synthesis of an important intermediate of the drug, acrivastine, on a gram scale. Notably, this is the first time that fluorescein dimethylammonium has been used to catalyze the Minisci-type C-H decarboxylative acylation reaction. The mechanism of decarboxylative acylation was studied by capturing adducts of acyl radicals and 1,1-diphenylethylene to confirm a radical mechanism. The disclosed catalytic system provides a green synthetic strategy for decarboxylative acylation without the use of additional oxidants or metal catalysts.

Automated summary

This study reports the development of a visible-light-induced catalytic system for the decarboxylative acylation of pyridine N-oxides with alpha-oxocarboxylic acids, using fluorescein dimethylammonium as a new type of photocatalyst. A series of 2-arylacylpyridine N-oxides were selectively synthesized by controlling the polarity of the reaction solvent. The disclosed catalytic system provides a green synthetic strategy for decarboxylative acylation without the use of additional oxidants or metal catalysts.