Toward a Formal Synthesis of Laureatin: Unexpected Rearrangements Involving Cyclic Ether Nucleophiles

Laureatin, a metabolite of the red algae <i>Laurencia nipponica</i>, has shown potent activity as a mosquito larvicide. The two previously published syntheses of laureatin involved an initial preparation of the 8-membered cyclic ether, followed by formation of the oxetane ring. Our strategy was the reverse, i.e., to utilize an oxetane as the framework to construct the larger ring. During this work, attempted <i>N</i>-bromosuccinimide (NBS)-mediated cyclization of oxetane alcohol <b>17</b>, prepared from readily accessible 2-methyleneoxetane <b>12</b>, yielded epoxytetrahydrofuran <b>19</b> rather than the expected laureatin core. Further derivatization of <b>19</b> yielded <i>trans</i> fused bis-tetrahydrofuran <b>32</b>. The synthesis of <b>19</b> and <b>32</b>, as well as structural and stereochemical elucidation studies, are described