Suzuki-Miyaura homocoupling of naphthyl triflates using bis(pinacolato)diboron: approaches to the biaryl skeleton of crisamicin A

Homocoupling of naphthyl triflates 27, 16, 17 to the respective binaphthyls 28, 31 and 35 has been achieved in a one-pot procedure using bis(pinacolato) diboron and PdCl2(dppf). Use of potassium acetate as the base provides access to the initial naphthylboronate intermediates whereas the stronger base potassium phosphate is required in order to promote subsequent coupling of the naphthylboronate with a second equivalent of the naphthyl triflate. Attempts to convert binaphthyl 35 into bis-acetylnaphthalene 14, a key intermediate for the synthesis of the dimeric pyranonaphthoquinone antibiotic crisamicin A 2, via double Fries rearrangement of bis-acetate 37 derived from binaphthyl 35, were unsuccessful. Attempts to introduce the acetyl groups at C-7 and C-7' on bis-acetylnaphthalene 14 via Fries rearrangement of the monomeric precursors 21 and 15, before effecting homocoupling to a biaryl were unsuccessful. Introduction of an acetyl group via initial bromination ortho to the hydroxyl group in naphthol 18, which bears an electron rich benzyl ether at C-7, was plagued by the formation of phenolic coupling product 42 and naphthoquinone 43. Bromination of naphthol 45, bearing a less electron rich triflate group at C-7, also afforded binaphthol 47 resulting from phenolic coupling as well as naphthoquinone 48 when using N-bromosuccinimide at low temperature.