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

Abstract

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.

Key words

enolate - aldol reaction - tin(IV) - stereoselective assembly - domino process

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10

Schmittel, M.; Haeuseler, A.; Henn, W.; Ghorai, M. K.; Koy, T. manuscript in preparation.

12

Engelen, B.; Deiseroth, H.-J.; Panthöfer, M.; Schlirf, J. private communication.

22

Proven also by x-ray structure analysis: Deiseroth, H.-J.; Schlirf, J. personal communication.