MacMillan DW. C,
Overman LE.
* University of California, Irvine, USA
Enantioselective Total Synthesis of (–)-7-Deacetoxyalcyonin Acetate. First Synthesis of a Eunicellin Diterpene.
J. Am. Chem. Soc. 1995;
117: 10391-10392
Key words
eunicellin diterpenes - Prins–pinacol rearrangement - photolytic deformylation - Nozaki–Hiyama–Kishi reaction
Significance
The eunicellin diterpenes feature a synthetically challenging tricyclic ring system, including a hydroisobenzofuran and oxonane subunit. MacMillan and Overman reported in 1995 the first synthesis of a member of this natural product family in asymmetric fashion, confirming the relative and absolute configuration proposed by the isolation team. Highlights of this synthesis include use of a Prins–pinacol rearrangement to access the hydroisobenzofuran core as well as a photolytic deformylation of a β,γ-desaturated aldehyde.
Comment
The synthesis commences with regioselective opening of A, which was converted into aldehyde E in three steps. Dienyl iodide F was accessed in three steps starting with (S)-carvone. Fusing the two fragments set the stage for Prins–pinacol rearrangement, affording I as a single stereoisomer. Deprotection and photolytic deformylation afforded intermediate J. The final oxonane ring was constructed using Nozaki–Hiyama–Kishi coupling, the natural product in two additional steps.
