Synthetic studies toward a biomimetic linear precursor of hirsutellones

In this paper we describe our efforts to synthesize the polyunsaturated part of a putative linear precursor of hirsutellones from (R)-citronellal, characterized by a terminal (E,Z,E)-triene alcohol. The geometry of this last moiety was installed by the alkyne reduction of an ene-yne-ene, under the Boland conditions [Zn(Ag,Cu), MeOH]. Under these conditions, we found that the presence of a diol functionality at the opposite of the linear chain, facing the alkyne, was necessary for the success of the reduction, an effect attributed to the chelation of an activated zinc species. Then one-pot diol cleavage-Wittig olefination allowed for further functionalization into a valuable αβ,-unsaturated ester or Weinreb amide.