Asymmetric synthesis of hexapropionate synthons by sequential enantiotopic group selective enolization of meso diketones.

Meso 1,9-diketones (six to seven stereocenters) are readily obtained by stepwise or simultaneous two-directional aldol reactions of tetrahydro-4H-thiopyran-4-one with a thiopyran-derived aldehyde or dialdehyde. Enantioselective enolizations of these diketones with the lithium amide from (R,R)-bis(1-phenylethyl)amine occur with simultaneous kinetic resolution to give the mono-TMS enol ethers in >90% yields (BORSM) and >95% ee. The products are applicable to polypropionate synthesis. [reaction: see text]

Enantioselective direct intermolecular aldol reactions with enantiotopic group selectivity and dynamic kinetic resolution.

[reaction: see text] Proline-catalyzed aldol reactions of tetrahydro-4H-thipyranone with racemic 1,4-dioxa-8-thia-spiro[4.5]decane-6-carboxaldehyde and with meso/dl 1,4-dioxa-8-thiaspiro[4.5]decane-6,10-dicarboxaldehyde proceed with dynamic kinetic resolution and give single adducts in good yields with excellent ee's. The high enantiotopic group selectivity results from the high intrinsic diastereoface selectivity of the aldehydes. These reactions significantly extend the scope of the enantioselective direct aldol reaction and constitute simple and efficient syntheses of useful tetrapropionate synthons.