Total Synthesis of Dihydroclerodin from (R)-(−)-Carvone

The first total synthesis of the natural enantiomer of the insect-antifeedant dihydroclerodin ( 1 ) and lupulin C ( 40 ) has been achieved starting from ( R )-(−)-carvone ( 2 ). In the applied strategy, the hexahydrofuro[2,3- b ]furan moiety was introduced in an early stage of the synthesis. The correct configuration at C-9, C-11, C-13, and C-16 was established by application of a remarkably diastereoselective Mukaiyama reaction. The desired configuration at C-10 was obtained by catalytic reduction of the intermediate enone 21 . After annulation of the second ring, the structural features at C-4, C-5, and C-6 were introduced. The successful finishing of the synthesis included a Chugaev elimination to give the exocyclic double bond at C-4 that is present in lupulin C. Oxidation of this double bond with m -CPBA afforded dihydroclerodin.