Stereospecific Pd(O)-catalyzed malonate additions to allylic hydroxy phosphonate derivatives: a formal synthesis of (-)-enterolactone.

A combination of cross-metathesis and malonate addition was applied to a formal synthesis of the mammalian lignan enterolactone 5. The cross-metathesis of alkene 6 and phosphonate 3a gave the substituted allylic phosphonate 3d. The palladium-catalyzed addition of malonate 10d to the allylic phosphonate 3d was stereospecific and highly regioselective and yielded the vinyl phosphonate 11d. The vinyl phosphonate 11d was converted in two steps into the lactone 14, a known intermediate in the synthesis of enterolactone 5.