The four stereoisomers of 2-oxazolidinone 5-substituted with 1-methyl-2-pyrrolidinyl (1), of 1,4-benzodioxane 2-substituted with the same residue (2) and of the nor-methyl analogue of this latter (2a) were synthesized as candidate nicotinoids. Of the 12 compounds, two N-methylated pyrrolidinyl-benzodioxane stereoisomers, namely those with the same relative configuration at the pyrrolidine stereocentre as (S)-nicotine, bind at alpha4beta2 nicotinic acetylcholine receptor with submicromolar affinity. Consistently with the biological data, docking analysis enlightens significant differences in binding site interactions not only between 1 and 2, but also between 2 and 2a and between the stereoisomers of 2 accounting for the critical role played, in the case of the pyrrolidinyl-benzodioxanes, by the chirality of both the stereolabile and stereostable stereogenic atoms, namely the protonated tertiary nitrogen and the two asymmetric carbons.