Synthesis of Nonsymmetrical 3,3′-Bicoumarins: Total Synthesis of Arteminorin C, 3,3′-Biisofraxidin, and Biscopoletin

A strategy to access nonsymmetrical 3,3'-bicoumarins employing two consecutive Perkin reactions is reported. This approach is based on the initial formation of coumarin acetic acid from a salicylaldehyde derivative through a Perkin reaction. A second Perkin condensation between the previously formed coumarin acetic acid and a new functionalized salicylaldehyde allows the formation of nonsymmetrical 3,3'-bicoumarins. Using this approach, 17 nonsymmetrical and two symmetrical 3,3'-bicoumarins were prepared in yields ranging from 30% to 86%, and natural products arteminorin C, 3,3'-biisofraxidin, and biscopoletin were obtained.