Solid‐Phase Synthesis of [5.5]‐Spiroketals

An efficient and reliable multi‐step synthesis of 251 natural product‐like [5.5]‐spiroketals on solid supports has been developed. As central key step, a double intramolecular hetero‐Michael (DIHMA) reaction to alkynones was applied. The sequence allows for introduction of numerous substituents on the scaffold and for variation of stereochemistry. [5.5]‐Spiroketals bearing an additional ketone were obtained in high overall yields. Further diversification was achieved by reduction of the ketone and reductive amination using polymer‐supported borohydride, Grignard reaction and conversion to oxime derivatives in the solution phase.