Total synthesis of 1,2,11,12E-tetradehydrohardwickiic acid

Abstract

Clerodane diterpenoids are a large class of natural products found in various species and exhibit a wide range of biological activities. trans-Clerodanes, which feature a trans-decalin core structure, are the most common subfamily of clerodane diterpenoids. Previously, we have developed a tail-to-head cyclization strategy via a titanium(III) catalyzed alkyne terminated radical polyene cyclization to synthesis C18 non-oxidized trans-clerodanes and sesquiterpene (hydro)quinones with a similar trans-decalin skeleton. In this communication, we reported the first asymmetric total synthesis of 1,2,11,12E-tetradehydrohardwickiic acid, a C18 oxidized trans-clerodane, through the product of titanium(III) catalyzed tail-to-head polyene cyclization of the derivative of farnesol. A hydroxyl group directed hydrogenation of alkene, an E-selective hydrobromination of terminal alkyne, and a Suzuki coupling were the key steps of the synthesis.