Total Synthesis of Clerodin.

The first and asymmetric total synthesis of clerodin, the earliest isolated clerodane diterpenoid, has been achieved by tail-to-head cyclization and modular synthetic strategies. The C19 oxidized trans-decalin core was constructed via a tail-to-head cyclization of an epoxide ene-yne compound containing an internal oxygenated methyl-bearing alkene. This process involved a titanium(III) catalyzed epoxide ring-opening/ene-yne cyclization. The furan fragment was assembled through a metallaphotoredox-enabled deoxygenative coupling of an alcohol precursor. A SmI2-mediated elimination of a pre-installed acetal established the 2,3-dihydrofuran motif.