A conceptually novel approach to hetero Diels-Alder adducts of carbonyl compounds is described using as the key steps an antibody-mediated kinetic resolution of hydroxyenones followed by a ring-closure process. Various beta-hydroxyenones proved to be very good substrates for antibodies 84G3- and 93F3-catalyzed retro-aldol reactions, allowing the preparation of highly enantiomerically enriched (up to 99% ee) precursors of pyranones. An attractive feature of this methodology is the possibility to convert these acyclic-enantioenriched beta-hydroxyenones into tetrahydropyranones by a conventional Michael-type addition procedure or into the corresponding dihydropyranones using an alternative palladium-catalyzed oxidative ring closure. For the palladium-mediated cyclization, a biphasic system has been implemented that allows the direct preparation of enantiopure dihydropyranones from the corresponding racemic aldol precursors using a sequential antibody-resolution/palladium-cyclization strategy, without isolation of the intermediate enantioenriched hydroxyenones. This bioorganic route is best applied to the preparation of hetero Diels-Alder adducts otherwise derived from less nucleophilic dienes and unactivated dienophiles.

[reaction: see text] A palladium(II)-mediated oxidative cyclization was found to be effective for the preparation of structurally diverse 2,3-dihydro-4H-pyran-4-ones from the corresponding beta-hydroxyenones. Attractive features of this transformation include the ready availability of the starting enones, the regiocontrol, and the easy access of enantiopure 2,3-dihydro-4H-pyran-4-one from the corresponding enantiopure enone.

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2005 Pyran derivatives R 0340A Catalytic Asymmetric Bioorganic Route to Enantioenriched Tetrahydroand Dihydropyranones. -A conceptually novel approach towards tetrahydro-and dihydropyranones is presented, involving an antibody-mediated kinetic resolution of β-hydroxyenones (I) as key step. A diversity of β-hydroxyenones is tolerated as substrate, but those containing longer alkyl chains at the double bond are unreactive. This drawback can be overcome by introduction of the alkyl chain by metathesis into enantiopure (Ia) after kinetic resolution [cf. (III)]. The enantioenriched β-hydroxyenones are converted to the corresponding tetrahydrohydropyranones (IV) and (V) by TmsOTf--mediated cyclization or to dihydropyranone (VI) by Pd-Cu-catalyzed cyclization. -(BAKER-GLENN, C.; HODNETT, N.; REITER, M.; ROPP, S.; ANCLIFF, R.; GOUVERNEUR*, V.; J.