Four-component cyclocondensation acetate

Four-component cyclocondensation of 1, aromatic aldehydes, mal-ononitrile, and ammonium acetate proceeded under MW irradiation in solvent-free conditions to give highly functionalized hexahydroquino-lines in excellent yield. The crystal structure of 2-amino-3-cyano-4-phe-nyl-7,7-dimethyl-5-oxo-l, 4,5,6,7,8-hexahydroquinoline was determined (06JHC985). 

MUller reports a four component, one-pot synthesis of pyridines <02TL6907>. For example, aryl halide 15 and propargylic alcohol 16 were combined in the presence of copper and palladium to afford enone 17. The addition of cyclic enamine 18 led to Michael addition and the subsequent cyclocondensation was achieved by adding ammonium chloride and acetic acid (19—>20). Other multicomponent approaches to substituted pyridines have been reports by Litvinov <02RCBIE362>, Elkholy <02SC3493> and Veronese <02T9709>. 

A four-component reaction involving tandem indium chloride-catalyzed cyclocondensation of ammonium acetate 124, glyoxal derivatives 125,2-azidobenzaldehyde derivatives 126, and propargylamines 127 followed by intramolecular azide-alkyne 1,3-dipolar cycloaddition reactions afforded highly functionalized benzo-imidazo-triazolodiazepines 128 (130L4492). 

Yan et al. (2007) reported that polysubstituted annulated pyridines can be synthesized in high yields by four-component, one-pot cyclocondensation reactions of N-phenacyl pyridinium bromide, aromatic aldehydes, acetophenones or cyclic ketones in the presence of ammonium acetate and acetic acid, assisted by microwave irradiation. Cyclic ketones with two a-CH groups yield annulated pyridines with additional a-benzylidene groups, which are derived in situ from double aldol condensation of cyclic ketones with two moles of aromatic aldehydes. 

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