Application of a [3+2] annulation reaction to the total syntheses of the annonaceous acetogenins

The application of a Lewis acid catalyzed [3+2] annulation reaction of chiral nonracemic allylsilanes and aldehydes has been applied to the total syntheses of members of the acetogenin family of natural products. The first project entailed the synthesis of asimicin using two sequential chelate-controlled annulation reactions to assemble the bis-tetrahydrofuran core of the natural product. The annulation reaction was found to be an efficient method for assembling this structure type. An improved method for protiodesilylation of the bis-tetrahydrofuran intermediates was also investigated.; The second project investigated using the annulation reaction to make several diastereomers of the bis-tetrahydrofuran structure. By modifying the structure of the tetrahydrofuran aldehydes used in the annulation reaction, three additional diastereomers of the bis-tetrahydrofuran structure were synthesized. The annulation reaction was found to be successful in the kinetic resolution manifold. This phenomenon was employed in the total synthesis of bullatacin.