Asymmetric Total Synthesis of (+)-Waihoensene
Asymmetric Total Synthesis of (+)-Waihoensene.
J. Am. Chem. Soc. 2020;
15. Mai 2020 (online)
Key words(+)-waihoensene - Conia-ene reaction - Pauson−Khand reaction - Wittig olefination - intramolecular HAT reaction
Huang, Yang, and co-workers report the asymmetric synthesis of (+)-waihoensene in 15 steps. Waihoensene features a congested [6,5,5,5] tetracyclic core, containing four contiguous quaternary carbons and a cis-fused six-membered ring.
In five steps, enone A is transformed into G, which undergoes diastereoselective Conia-ene reaction to H. Enyne H is elaborated to J through a Pauson–Khand reaction, followed by a nickel-catalyzed 1,4-addition. Reduction of the exocyclic double bond is achieved by Fe(acac)3/PhSiH3-mediated intramolecular HAT reaction to give N. Shortly after the publication of this synthesis, Snyder and co-workers reported another synthesis of this natural product following a very similar strategy (Angew. Chem. Int. Ed. 2020, DOI: 10.1002/anie.202004177).