Stereoselective Assembly of Three Different Carbonyl Components by Two Successive Aldol Reactions Using Group IVa and IVb Metals

The rational design of a highly stereoselective E1+E2+A aldol-aldol route (using two different enolates E1,E2 and one aldehyde A) to tetrahydropyran-2,4-diols was based on screening group IVa and IVb metal bound enolate/aldolate hybrides in their potential to undergo aldol vs. retro-aldol reactions. Tin(IV) proved superior to all other metal ions since only a negligible amount of retro-aldol reaction is triggered. In the following, this property of tin(IV) was exploited to set up a highly stereoselective E1+E2+A route that allows the assembly of tetrahydropyran-2,4-diols with a wide variety of substituent patterns. The results obtained for open-chain enolates lends weight to the argument that a chair-boat transition state occurs in the last aldol step, while a boat-boat transition state may operate in the presence of cyclic enolates.