First total synthesis of palmarumycin C₆ based on double oxa-michael addition of 1,8-dihydroxynaphthalene to 3-bromo-1-indenone

Synthetic studies on palmarumycin C₆ with a naphthyl acetal at the C-3 position in 4,7-dihydroxy-1-indanone as a lower homologue of spirobisnaphthalenes are described herein. We investigated three approaches: 1) Nazarov cyclization of benzoylketene acetal, 2) intramolecular Friedel-Crafts acylation of naphtho[1,8-de]-1,3-dioxin-2-aryl-2-acetic acid chloride, and 3) double oxa-Michael addition of 1,8-dihydroxynaphthalene to 3-bromo-1-indenone. The last approach successfully afforded the natural product after the removal of acetates that serve as protecting groups for phenolic hydroxyls under acidic conditions.