Biomimetic Synthesis of Natural and "Unnatural" Lignans by Oxidative Coupling of Caffeic Esters

The metal-mediated oxidative coupling of caffeic acid esters has been employed in the biomimetic synthesis of dimeric lignans and neolignans. Phenethyl and methyl caffeate esters were used as substrates and MnO(2), Mn(OAc)(3) and Ag(2)O as oxidative coupling agents. The manganese-mediated reactions afforded in good yields the unusual benzo[kl]xanthene lignans 6 and 15 as the major products accompanied by minor amounts of the aryldihydronaphthalene lignans (+/-)-7 and (+/-)-16. When Ag(2)O was employed, the neolignan (+/-)-17 was obtained as the major product. This biomimetic route was also used to obtain the natural benzo[kl]xanthene lignans rufescidride (9) and mongolicumin A (10). A computational study of the coupling reactions was also carried out. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)