Utilization of the Thorpe–Ingold Effect in the Synthesis of Cyclooctanoid Ring Systems via Anionic 6-<i>exo</i>-<i>dig</i> Cyclization/Claisen Rearrangement Sequence
Weston C. DeLomba, Elizabeth A. Stone, Kimberly A. Alley, Victoria Iannarone, Emily M. Tarsis, Sami I. Ovaska, Timo V. Ovaska
Abstract
We demonstrate a facile approach for the synthesis of gem-disubstituted cyclooctanoids, a motif found in several biologically active compounds. Appropriately substituted 1-alkenyl-5-pentyn-1-ols bearing gem-dialkyl substituents at either the C2, C3, or C4 position serve as useful precursors to a number of cyclooct-4-enone derivatives via a tandem, microwave-assisted oxyanionic 6-exo-dig cyclization/Claisen rearrangement reaction. gem-Dialkyl activation is necessary for these reactions to occur, as unactivated 1-alkenyl-5-pentyn-1-ols fail to undergo 6-exo-dig cyclization under the conditions employed. Further application of the methodology to the corresponding gem-dialkoxy system was also explored to facilitate access to more complex carbocycles.