Synthesis of the C20–C32 Tetrahydropyran Core of the Phorboxazoles and the C22 Epimer via a Stereodivergent Michael Reaction

A stereoselective synthesis of the C20–C32 tetrahydropyran core of the phorboxazoles has been achieved in only seven steps and in a 31% overall yield. The C22 epimer was also synthesized. The key step was a silyl ether deprotection/oxy-Michael cyclization. When this step was conducted under Brønsted acid conditions, the C20–C32 core was formed with the desired 2,6-<i>cis</i>-stereochemistry. However, when the silyl ether deprotection/oxy-Michael cyclization was conducted under fluoride conditions buffered with acetic acid, the C22 epimer of the core was the sole product