Efficient Synthesis of 1-Amino-2-naphthalenecarboxylic Acid Derivatives via a Sequential Michael Addition/Enolate−Nitrile Coupling Route and Its Application to Facile Preparation of 9-Amino Analogues of Arylnaphthofuranone Lignans

Abstract

The reaction of 2-(alpha-lithioalkyl)benzonitriles, generated in situ by treatment of 2-alkylbenzonitriles with LDA in diglyme, with alpha,beta-unsaturated carboxylates and nitriles produced 1-amino-3,4-dihydro-2-naphthalenecarboxylates and carbonitriles in 54-98% yields through Michael addition of the lithio nitriles to alpha,beta-unsaturated carboxylic acid derivatives, followed by zinc iodide-promoted intramolecular enolate-nitrile coupling of the resulting enolate intermediates. The dihydronaphthalenecarboxylic acid derivatives were converted to the corresponding 1-amino-2-naphthalenecarboxylic acid derivatives in 43-99% yields on dehydrogenation with palladium on activated carbon in refluxing p-cymene. Subsequently, we showed that, by using a similar reaction sequence, 9-amino analogues of arylnaphthofuranone lignan derivatives {9-amino-4-arylnaphtho[2,3-c]furan-1(3H)-ones} could also be prepared from 2-(arylmethyl)benzonitriles and furan-2(5H)-one in good overall yields (59-61%).