Synthesis of the C3−C19 Segment of Phorboxazole B

Three segment-coupling Prins approaches to the C3−C19 segment of phorboxazole B have been developed. One successful strategy utilized a novel TMSBr-mediated cyclization that proceeded with complete axial selectivity. Displacement of bromide with cesium acetate provided the C13 hydroxyl stereocenter of 22. Additionally, treatment of α-acetoxy ether 20 with TFA enabled a more concise synthesis of the C3−C19 target 13 by allowing direct access to the equatorial alcohol.