An oxidative entry into the amido trioxadecalin ring system

The amido trioxadecalin ring system is a key structural component of the architecturally interesting anticancer and immunosuppressive agents of the mycalamide, theopederin, and onnamide families of natural products. We report a new entry into this structure in which a mixed acetal serves as a surrogate for a formaldehyde hemiacetal in an addition to an oxidatively generated acyliminium ion. The stereochemical outcome of this process can be explained by the conformational preferences of the product ring system. [reaction: see text]