A Catalytic Asymmetric Bioorganic Route to Enantioenriched Tetrahydro-and Dihydropyranones

摘要

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.