| ?-Aminoketone is an important building block in organic synthesis, which can easily be converted to ?,?-unsaturated ketone, 1,3-amino alcohol and other functionalized ketone.?-aminoketone compounds exhibit numerous biological activities including anti-inflammatory,anticancer,anti-tuberculosis, anti-bacterial,analgesic and antitussive activities. Various methods for the preparation of ?-aminoketone have been reported. Mannich-type reaction might be the most popular methodology for the one-pot construction of ?-aminoketone.But the exploration of new synthetic methodology for this privileged structure is still an important and challenging task.The main research work is Fe(OTf)3-catalyzed tandem Meyer-Schuster rearrangement/intermolecular hydroamination of 3-aryl propargyl alcohols and nitrogen nucleophiles for the synthesis of ?-aminoketones.The effects of different aromatic rings and substituents at the a-position of the hydroxyl group of 3-aryl propargyl alcohols on the reaction were investigated. Results showed that propargyl alcohols without bulky groups ? to the hydroxyl group underwent the transformation smoothly. Propargyl alcohols which contained strong electron-withdrawing substituents could not react. Sulphonamides exhibited the higher reactivity than amides as the nitrogen nucleophiles and the transformation of ?-aminoketones were finished in shorter reaction time and higher yields. At the same time we also studied the mechanism of the reaction and we proposed a possible mechanism of present reaction. Finally, racemic fluoxetine was efficiently accessed with the present reaction as the first step. This novel synthesis of ?-aminoketones probable proceeded a Fe(OTf)3-catalyzed Meyer-Schuster rearrangement of 3-aryl propargyl alcohols,followed by a intermolecular hydroamination between nitrogen nucleophiles and ?, ?-unsaturated ketones. |
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