ASYMMETRIC-SYNTHESIS OF THE DITERPENOID MARINE TOXIN (-ACETOXYCRENULIDE())

An enantioselective route to the marine toxin (+)-acetoxycrenulide is described. The early stages of the synthesis feature the conversion of (R)-citronellol into a butenolide whose sole stereogenic center is pr ovided by the terpenic alcohol. Three contiguous chiral carbon atoms a re subsequently set in the requisite absolute configuration by conjuga te addition of an enantiopure allylphosphonamide reagent. The resultin g product is transformed during several steps into a primary selenoxid e whose thermal activation in dimethylacetamide at 220 degrees C promo tes sequential 1,2-elimination and Claisen rearrangement. The cyclooct enone core of the target is formed in this step. The final stages of t he synthesis involve a series of fully stereoselective reactions inclu ding Simmons-Smith cyclopropanation and controlled Dibal-H reduction. The naturally occurring dextrorotatory enantiomer of acetoxycrenulide was ultimately acquired.