Stereoselective Synthesis of Tetrahydropyrans through Tandem and Organocatalytic Oxa-Michael Reactions: Synthesis of the Tetrahydropyran Cores of ent-(+)-Sorangicin A

Tandem and organocatalytic oxa-Michael reactions of a,beta-unsaturated aldehydes were explored for the stereoselective synthesis of structurally complex tetrahydropyrans. Thestereoselective synthesis of 2,6-trans-tetrahydropyrans, which are thermodynamically unfavorable, was accomplished through a reagent-controlled, organocatalytic oxa-Michael reaction. A temperature-dependent configurational switch allowed the preparation of both 2,3-trans-2,6-trans- and 2,3-cis-2,6-cis-tetrahydropyrans from a common substrate. This switch was then used to synthesize the precursors of the C21C29 and C30C37 fragments of ent-(+)-sorangicin A.