Synthesis of aromatic spiroacetals related to γ-rubromycin based on a 3H-spiro[1-benzofuran-2,2′-chromane] skeleton

The synthesis of a series of aromatic 5,6-benzannelated and naphthyl-benzannelated spiroacetals related to the spiroacetal unit present in the quinonoid antibiotic γ-rubromycin is reported. The key steps include the use of Sonogashira coupling to construct an aryl acetylene that is coupled to an aryl aldehyde forming a propargyl alcohol intermediate. Hydrogenation of the resultant alkynol followed by oxidation produces a masked dihydroxyketone that upon treatment with silica-supported sodium hydrogen sulfate undergoes concomitant deprotection and cyclisation to afford the desired fused aromatic spiroacetal.