Utilization of the Thorpe-Ingold Effect in the Synthesis of Cyclooctanoid Ring Systems via Anionic 6-- Cyclization/Claisen Rearrangement Sequence.

We demonstrate a facile approach for the synthesis of -disubstituted cyclooctanoids, a motif found in several biologically active compounds. Appropriately substituted 1-alkenyl-5-pentyn-1-ols bearing -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-- cyclization/Claisen rearrangement reaction. -Dialkyl activation is necessary for these reactions to occur, as unactivated 1-alkenyl-5-pentyn-1-ols fail to undergo 6-- cyclization under the conditions employed. Further application of the methodology to the corresponding -dialkoxy system was also explored to facilitate access to more complex carbocycles.