The Synthesis of 5-Hydroxy-3-methylnaphtho[2,3-c]furan-4,9-dione and 5,8-Dihydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione

5-Hydroxy-3-methylnaphtho[2,3-c]furan-4,9-dione (1), a metabolite isolated from Aloe ferox and Bulbine capitata, has been synthesized by a sequence involving an annulation reaction between the anion of 4-methoxy-3-oxo-1,3-dihydroisobenzofuran-1-carbonitrile (8) and (E)-pent-3-en-2-one, followed by subsequent construction of the furan ring through allylic bromination, hydrolysis, and dehydration as the key steps. The formation of several unusual products observed in annulation reactions between (8) and O-protected derivatives of (E)-5-hydroxypent-3-en-2-one (9) can be rationalized by invoking the intermediacy of a reactive o-quinone methide. 5,8-Dihydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione (2), another naturally occurring naphtho[2,3-c]furan-4,9-dione, has been prepared by a Friedel–Crafts acylation of 1,4-dimethoxybenzene with 2-methylfuran-3,4-dicarbonyl dichloride. Arguments are presented that 5,8-dihydroxynaphtho[2,3-c]furan-4,9-dione is a better structural representation than the alternative 4,9-dihydroxynaphtho[2,3-c]furan-5,8-dione tautomer in such systems, as the latter would contain a reactive isobenzofuran moiety.