Stereoselective Synthesis of 2,6-trans-Tetrahydropyrans via Tandem Horner-Wadsworth-Emmons Olefination of
Katsiaryna A Nekrasava1, Vitaly Syakhovich2, Uladzimir S Masiuk1
1Belarusian State University, Department of Chemistry, Leningradskaya 14, 220006Minsk, Belarus.
Abstract:
Tandem approaches based on intramolecular oxa-conjugate cyclization of ζ-hydroxy-α,β-unsaturated carbonyl compounds provide an efficient route to 2,6-disubstituted tetrahydropyrans (THPs). However, existing methods are limited to the synthesis of thermodynamically favored 2,6-cis-isomers. Here, we report a tandem stereoselective synthesis of 2,6-trans-THPs via a Horner-Wadsworth-Emmons olefination of lactols/intramolecular oxa-conjugate cyclization sequence under kinetically tailored reaction conditions. The developed protocol affords 4-methylene-2,6-trans-disubstituted THPs, bearing functionalized substituents, in good yields (50-84%) and with high diastereoselectivities (dr up to 95:5). The utility of the method was demonstrated through synthetic modifications of the 2,6-trans-THPs and the asymmetric synthesis of the natural products diospongins A and B.
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