6-nitro-1,2,3,4-tetrahydroquinolines by a tandem reductive amination-S,Ar reaction

摘要

A tandem reductive amination-SNAr reaction has been developed for the synthesis of 6-nitro-1,2,3,4-tetrahydroquinolines. Treatment of 4-(2-fluoro-5-nitrophenyl)-2-butanone or 3-(2-fluoro-5-nitrophenyl)propanal with primary amines and sodium cyanoborohydride in methanol at room temperature provided good to excellent yields of the substituted tetrahydroquinolines. The reaction proceeded best with the ketone substrate using primary amines that were unbranched at the alpha-carbon. The aldehyde also produced the target heterocycles, but these were accompanied by 10-15% of the uncyclized side chain reductive amination products.