Double furofuran annulation to a bis-naphthoquinone: an approach to dimeric pyranonaphthoquinones

The preparation of bis-naphthoquinone 7, a key intermediate in the synthesis of dimeric pyranonaphthoquinones related to the actinorhodins is described. Initial efforts directed to 7 which focussed on a double Fries rearrangement of bis-acetate 14 to 2-acetylnaphthol 13 were low yielding. Use of a Stille coupling reaction between dimeric bromonaphthalene 20 and (alpha-ethoxyvinyl)tri-n-butyltin 19 as a means to introduce the acetyl groups at C-2 was also low yielding. The optimum route to bis-naphthoquinone 7 involved the synthesis of 2-acetylnaphthol 13 from bromide 25 using a Suzuki-Miyaura coupling. Addition of 2-trimethylsilyloxyfuran to bis-naphthoquinone 7 afforded the bis-annulation adducts 30,31 which underwent double oxidative rearrangement to bis-lactols 32,33. Reduction of the bis-lactols to bis-ethers 34,35 completed the first synthesis of a dimeric pyranonaphthoquinone.