An Efficient Friedel-Crafts/Oxa-Michael/Aromatic Annulation: Rapid Access to Substituted Naphtho[2,1-b]furan, Naphtho[1,2-b]furan, and Benzofuran Derivatives

Substituted naphthofurans and benzofurans are easily accessible by treatment of naphthols/substituted phenols with nitroallylic acetates through a substitution-elimination process promoted by cesium carbonate. Reactions between naphthols and aromatic/heteroaromatic-substituted nitroallylic acetates gave the desired functionalized naphthofurans in high to excellent chemical yields (14-97%). On the other hand, treatment of phenol derivatives (i.e., 3-dimethylamino-, 3-methoxy-, and 3,5-dimethoxyphenol) with various nitroallylic acetates afforded the corresponding benzofurans in moderate to good chemical yields (24-91%). The reaction proceeded through an interesting Friedel-Crafts S(N)2' process followed by intramolecular oxa-Michael cyclization and subsequent aromatization. A plot of log (k/k(H)) against Hammett constants sigma(P) showed satisfactory linearity with a positive rho value, indicating that the initial Friedel-Crafts-type S(N)2' process constituted the rate-determining step. This methodology has been applied to the synthesis of various novel C-2 and C-3 symmetric bis- and trisfurans by using catechol and phloroglucinol as the nucleophilic partners. The reactivity decreased when alkyl-substituted nitroallylic acetate systems were used. This might be related to the decreased electrophilic character of these substrates.