New methodology has been developed for the synthesis of so-called sapphyrins, pentapyrrolic 'expanded porphyrins'. An efficient approach involving acid-catalyzed condensation of 1,19-diunsubstituted a,c-biladienes and 3,4-dialkylpyrrole-2-carbaldehydes eliminates the preparation of bipyrrolic intermediates and allows the synthesis of sapphyrins with an unsymmetrical array of peripheral substituents. The β-substitution pattern of 2,3,13,17-tetraethyl-7,8,12,18,22,23-hexamethylsapphyrin has been unambiguously confirmed by single crystal X-ray crystallography. 1H NMR spectra of the dication salts of sapphyrins are strongly dependent upon the counterions, and the pattern of resonances observed in solution is related to the stacking interactions between the macrocycles.