An expedient synthesis of spiroketals: model studies for the calyculin C16-C25 fragment

A new short strategy to prepare the spiroketal fragment of calyculins is presented. A novel Seyferth-Gilbert type homologation of hindered lactols to the corresponding alkynes has been achieved for the first time. The spirocyclization was achieved efficiently via a DIHMA (double intramolecular hetero-Michael addition) process of this hindered ynone. The spirocyclization rate is not dependent on the stereochemistry of the alkoxy substituent in the oxolane ring.