Development of the tandem oxy-Copeene rearrangement and its application toward natural antibiotic tetrodecamycin

Abstract

This thesis explores the development of the tandem oxy-Cope/ene rearrangement and its application toward the synthesis of natural antibiotic tetrodecamycin. These studies have been carried out to better understand the chemical synthesis of decalin natural products, and provide a springboard from which further studies can be launched. The first part of the study focueses on the tandem oxy-Cope/ene rearrangement and the unravelling of the intricate aspects governing the selectivity, stereochemistry, and transition state conformers at play. As a result of this study, we have developed a general methodology for rapidly constructing decalins bearing a ring junction alcohol via cascade oxy-Cope/ene rearrangement of 1,2-divinyl cyclohexanols. The second part of this study involved the application of this methodology to the decalin skeleton present in tetrodecamycin. Described in this section is the development of the synthetic chemistry en route to the core of the natural product, along with the serendipitous discovery of a tandem oxy-Cope/Claisen/ene/Claisen rearrangement. Finally, the decalin core provided by the tandem rearrangement was fully functionalised to resemble that of the natural product (including all 6 contiguous stereocentres), and the synthetic efforts toward the completion of tetrodecamycin are described.