Bidirectional racemic synthesis of the biologically active quinone cardinalin 3

Readily available 2,2′,6,6′-tetramethoxy-1,1′-biphenyl was transformed in 14 synthetic steps into the natural product cardinalin 3 using a bidirectional approach. One of the key steps was the formation of the cis-1,3-dimethylnaphtho[2,3-c]pyran ring. (±)-1,1′-[6,6′- Diallyl-5,5′-bis(benzyloxy)-1,1′,3,3′-tetramethoxy-2, 2′-binaphthalene-7,7′-diyl]diethanol was treated with O2 in the presence of CuCl2 and catalytic PdCl2 to afford 5,5′-bis(benzyloxy)-7,7′,9,9′-tetramethoxy-1,1′,3, 3′-tetramethyl-1H,1′H-8,8′-bibenzo[g]isochromene. Hydrogenation of this compound afforded 7,7′,9,9′-tetramethoxy-cis- 1,3-cis-1′,3′-tetramethyl-3,3′,4,4′-tetrahydro-1H, 1′H-8,8′-bibenzo[g]isochromene-5,5′-diol in quantitative yield, which was converted in 3 steps to cardinalin 3. © The Royal Society of Chemistry.