| 2-Thioalkyl substituted furans were prepared by the cyclization of a carbonyl oxygen atom onto an intermediate thionium ion. Two separate protocols were developed to generate the reactive intermediates. In the first method, an acid catalyzed cyclization of ketenedithioacetals was employed as a rapid entry into carbon-substituted thio-furans. The dimethyl-(methylthio)sulfonium tetrafluoroborate (DMTSF) promoted cyclization of γ-dithiane carbonyl compounds represents another method for preparing thio-furans, including heteroatom substituted systems. The DMTSF procedure was used to generate heterocyclic annulated 5-amido-2-thiomethyl-furans which contain tethered unsaturation. When heated, these systems underwent a tandem intramolecular Diels-Alder/1,2-thiomethyl shift cascade to afford fused tricyclic systems possessing a perhydroindolone ring. Several structural features such as tether length, the presence of the amido carbonyl group within the carbon tether, and size of the annulated heterocycle were studied. The above methodology was utilized for a total synthesis of the stemona alkaloid (±)-stenine. The key feature of this synthesis involves the rapid construction of the tricyclic azepinoindole core using an intramolecular Diels-Alder/1,2-thiomethyl shift cascade sequence of an amido-thio-furan. |
