Strategies, Setbacks, and Successes in the Synthesis of (−)-Spiroleucettadine

Various
strategies toward the synthesis of the marine natural product
(−)-spiroleucettadine are described. In the original strategy,
a biomimetic inspired oxidation of a 2-imidazoline scaffold uncovered
unexpected reactivity, where benzylic oxidation followed by a Baeyer–Villiger
reaction was observed. The second generation approach examined oxidative
dearomatization of the phenol ring system first, where a competing
spirocyclization process was uncovered. Efforts to forge the scaffold
via a carbocation mediated benzyl migration were unsuccessful. Highlights
of the successful synthesis include two consecutive hypervalent iodine
reactions: the first formed the spirocyclic center and the second
facilitated installation of an acetate group at the C-5 position to
allow for subsequent introduction of the methyl amine side chain.