Construction of the Tricyclic Furanochroman Skeleton of Phomactin A via the Prins/Conia-Ene Cascade Cyclization Approach.

A substrate-controlled asymmetric Prins/Conia-ene cascade cyclization has been developed with In(OTf)3 in CH3CN from 0 to 70 °C. These conditions afforded very good yields of the 1-oxadecalin product in one pot and effectively suppressed the racemization of the 1-oxadecalin product with almost no enantiomeric excess (ee) loss. This cascade cyclization has been successfully employed for the construction of the highly functionalized 1-oxadecalin unit of phomactin A with an acyclic β-keto ester and an alkynal as the substrates via a one-pot operation (66% yield, single diastereomer). The 1-oxadecalin moiety has been readily converted to the tricyclic furanochroman skeleton of phomactin A via the epoxidation/dealkoxycarbonylation protocol under very mild conditions with 5296 yield in three steps. [ABSTRACT FROM AUTHOR]