A straightforward synthesis of a highly substituted biomassderived chiral pyrrolidine conveniently functionalized to obtain macrocycles through intramolecular "click" reactions is reported. The experimental difficulties encountered during the macrocyclization stage led us to conduct an extensive DFT study to understand the origins of the findings. The results suggest that the improper conformational landscape of the reactant precludes the pre-organization required to connect the reactive moieties. We propose that the cumulative Boltzmann amplitudes of reactive conformations (CBAR) prove to be a simple and useful parameter to predict the success or failure of related transformations.