Survey of Synthetic Approaches to Natural (Peyssonenynes) and Unnatural Acetoxyenediynes

Four convergent synthetic approaches to acetoxyenediynes have been explored to gain access to peyssonenynes A and B, which are natural products isolated from the red alga Peyssonelia caulifera. After optimization of the routes with a palmitic acid based model system, the synthesis of the peyssonenynes was completed by using, as the key steps, 1) Ni/Cu co-catalyzed cross-coupling of terminal alkynes, 2) Sonogashira cross-coupling, 3) the addition of a diynyl anion to a Weinreb amide, and 4) the previously reported CadiotChodkiewicz cross-coupling reaction. Because bulky amide bases stereoselectively provided the (E)- and (Z)-acetoxyenynes from the precursor ynones, the cross-coupling routes to obtaining the acetoxyenediynes by using these stereochemically homogeneous intermediates are comparable to the alternatives in which enolacetate formation of the acetoxyenediyne motif takes place at a late stage in the synthesis.