Metal-Free Intermolecular Coupling of Arenes with Secondary Amides: Chemoselective Synthesis of Aromatic Ketimines and Ketones, and N-Deacylation of Secondary Amides.
The direct transformation of common secondary amides into aromatic ketimines and aromatic ketones with C-C bond formation is described. The reaction can also be used for N-deacylation of secondary amides to release amines. This method consists of in situ amide activation with triflic anhydride and intermolecular capture of the resulting highly electrophilic nitrilium intermediate with an arene. The reaction is applicable to various kinds of secondary amides (electrophiles), but only electron-rich and moderately electron-rich arenes can be used as nucleophiles. Thanks to the use of bench stable arenes instead of reactive and basic organometallics as nucleophiles, the reaction proceeded with high chemoselectivity at the secondary amido group in the presence of a series of sensitive functional groups such as aldehyde, ketone, ester, cyano, nitro, and tertiary amido groups. The reaction can be viewed as a Friedel-Crafts-type reaction using secondary amides as acylating agents or as an intermolecular version of the Bischler-Napieralski reaction.
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, Collaborative Innovation Centre of Chemistry for Energy Materials (iChEM), College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, P. R. China.|State Key Laboratory of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, P. R. China.
Pei-Qiang
PQ
Huang
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, Collaborative Innovation Centre of Chemistry for Energy Materials (iChEM), College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, P. R. China.
Ying-Hong
YH
Huang
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, Collaborative Innovation Centre of Chemistry for Energy Materials (iChEM), College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, P. R. China.
Kai-Jiong
KJ
Xiao