Diastereoselective intramolecular oxidopyrylium–alkene [5 + 2]-cycloaddition of substrates with a β-chiral center on alkene tethers: synthesis of 8-oxabicyclo-[3.2.1]-octenone heterocycles

Abstract

We investigated the asymmetric intramolecular oxidopyrylium–alkene [5 + 2]-cycloaddition reaction of substrates bearing tethered alkenes containing β-chiral centers. The effect on the cycloadduct diastereoselectivity was examined for carbon chain tethered alkenes or alkoxy tethered alkenes with varying chain lengths that can form 5-, 6- and 7-membered rings. We also probed the effect of varying steric bulk on the β-chiral center substituents on cycloadduct diastereoselectivity. Various substrates with carbon chain tethered alkenes were synthesized using the Lewis acid mediated conjugate addition of an allyl group to furanyl enones. Reduction of the resulting ketones followed by the Achmatowicz reaction of furanyl alcohol provided oxidopyrylium–alkene substrates. The asymmetric [5 + 2]-cycloaddition proceeded with high diastereoselectivity for cycloadducts with five and six-membered rings. However, cycloadducts with a seven-membered ring showed no diastereoselectivity. Stereochemical models are provided to explain the high diastereoselectivity for five and six-membered products.