UC Santa Barbara

The tetracyclic natural product, tetrapetalone A has eluded chemists since its isolation in 2002. The complex structural features of this natural product provide a platform from which new synthetic methods can be developed. One approach to build tetrapetalone includes formation of a Nitrogen-Aryl bond. Despite the prevalence of this bond connection in natural and pharmaceutical compounds, previous methods to form Nitrogen-Aryl bonds were not applicable in our approach to the tetrapetalone A scaffold. To overcome this limitation and provide a different route to access compounds containing Nitrogen-Aryl bonds, we approached the problem with a different strategy. This divergent strategy relies upon distinct deprotonation conditions of a cyclic vinylogous amide to afford regioisomeric dienes. Each diene can then undergo a tandem Diels-Alder and retro-Diels-Alder sequence with a variety of acetylenic dienophiles to afford a range of multi-substituted aromatic products containing Nitrogen-Aryl bonds. The scope of this method and its application toward tetrapetalone A will be discussed. While investigating different synthetic approaches, our group also probed the reactivity of the tetramic acid C-5 position. When our group encountered limitations among the current methods to install vinyl groups at the C-5 position we turned to develop a more general vinylation strategy. Our progress toward a "vinylation reagent" is reported and future directions will be discussed.