Unsaturated malonyl esters underwent Pd-catalyzed intramolecular allylic alkylation to give 4-vinyl-substituted gamma-lactones. In contrast to the formerly studied cyclization of malonamides, this reaction could be achieved only with a substrate incorporating a suitably positioned silicon moiety, which directs the ionization toward the desired eta(3)-allylpalladium complex. The resulting 4-[dimethyl-(2-thienyl)silylvinyl]lactone could be subsequently engaged into Hiyama couplings with various iodoarenes, to give the corresponding 4-(alpha-styryl)-gamma-lactones. The use of a specifically substituted iodoarene generated an advanced tetracyclic lactone intermediate incorporating rings A-D of lignans belonging to the podophyllotoxin family. Subsequent electrophilic aromatic substitution with a variety of electron-rich arenes afforded the target picropodophyllin analogs.