Total Synthesis of (±)-Crokonoid A

We report the first total synthesis of (±)-crokonoid A, a highly oxidized and rearranged <i>ent</i>-kauranoid featuring a novel tricyclo[4.4.1.1^1,4]dodecane scaffold. The unique double bridged carbon skeleton was assembled by synthesis of the bicyclo[4.3.1]decane via nitrile-oxide dipolar cycloaddition. Salient features of this strategy are the effective construction of the bridged system and masking the twofold aldol motif as an isoxazoline. An unconventional bridgehead propargylation set the key quaternary stereocenter concomitant with the installation of the side chain. Subsequent cycloalkenylation led to construction of the bicyclo[3.2.1]octane, completing the carboskeleton. Strategic orchestration involving regio- and diastereoselective reactions furnished the unique oxidation pattern, thus completing the total synthesis.