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.