Zhao P, Beaudry CM * Oregon State University, Corvallis, USA
Enantioselective and Regioselective Pyrone Diels–Alder Reactions of Vinyl Sulfones:
Total Synthesis of (+)-Cavicularin.
Angew. Chem. Int. Ed. 2014;
DOI:
10.1002/anie.201406621
Key words
(+)-cavicularin - Suzuki cross-coupling - pyrone Diels–Alder reaction
Significance
(+)-Cavicularin, isolated from the liverwort Cavicularia densa, is a chiral cyclophane natural product. Because of its unusual molecular structure,
several total syntheses have been reported to date. Zhao and Beaudry report a conceptionally
different approach, which relies on an intramolecular enantioselective pyrone Diels–Alder
reaction with subsequent CO2 extrusion to generate the aromatic A ring of the natural product.
Comment
The synthesis commences with a remarkably selective one-pot three-component Suzuki
cross-coupling between dibromide B and boronic esters A and C. Coupling product D was further advanced to α-hydroxy pyrone E. In the presence of cinchona alkaloid F, this material underwent the desired Diels–Alder reaction to yield intermediate G, which immediately eliminated CO2 and phenylsufinic acid to generate H as a single regioisomer. Finally, reduction and protecting group removal yielded
(+)-cavicularin in 7.3% overall yield.
