Abstract Reaction of protoanemonin, 1 , with piperidine, dimethyl malonate anion, and lithium dimethyl- and dibutylcuprates are reported. Thus, while in the first case almost no regioselectivity is observed, in the other cases the obtained products are the result of nucleophilic attack to the exocyclic C-C double bond of 1 exclusively, giving the 1,6-adduct in the first step of the reaction. These adducts can evolve, with participation of unreacted protoanemonin in the reaction conditions, to polycyclic compounds, through 1,6-addition, alkylation and intramolecular Michael addition processes. Constitution of the compounds obtained have been assigned on the basis of spectral characteristics and mechanistic approaches. The behaviour of 1 in front of nucleophiles has been rationalized and generalized by means of experimental results and theoretical calculations.