A Scalable Synthesis of (R,R)-2,6-Dimethyldihydro-2H-pyran-4(3H)-one

A scalable synthesis of (R,R)-2,6-dimethyldihydro-2H-pyran-4(3H)-one is reported. Key to this strategy is the Ti(OiPr)4-catalyzed Kulinkovich cyclopropanation of silyl protected (R)-ethyl 3-hydroxybutanoate, and subsequent oxidative fragmentation of the cyclopropanol. The resulting vinyl ketone intermediate was then subjected to oxidative Heck cyclization to form the enone substrate required for conjugate addition. A diastereoselective copper-catalyzed Grignard addition procedure was implemented to install the requisite methyl group, with the inclusion of 1,3-bis(diphenylphosphino)propane and trimethylsilyl chloride greatly increasing the robustness of this process.