The multicomponent reaction of primary aromatic amines, aromatic aldehydes and biacetyl leads to 1,2,4,5-tetraarylpyrrolo[3,2-b]pyrroles in yields as large as 77% when catalyzed by iron(III) perchlorate. These new conditions enabled for the first time, the synthesis of pyrrolo[3,2-b]pyrroles from 5-membered heterocyclic aldehydes such as furan, thiophene, thiazole, and their benzo derivatives as well as from 1-aminonaphthalene, 3,5-bis(trifluoromethyl)aniline, and hexane-3,4-dione. Photophysical studies have revealed that pyrrolo[3,2-b]pyrroles possessing five-membered rings at positions 2 and 5 have large fluorescence quantum yields as well as bathochromicaly shifted absorption and emission compared to tetraphenyl-pyrrolopyrroles; the shift being particularly marked for both furan and benzofuran. Large Stokes shifts can be attained when substituents bearing multiple biaryl linkages are present at positions 2 and 5. The new fluorphores’ optical properties were rationalized through ab initio calculations relying on Time-Dependent Density Functional Theory (TD-DFT) and second-order Coupled Cluster (CC2) methods. These computational studies confirmed that low dihedral angles are the main cause for bathochromically shifted absorption and emission for pyrrolo[3,2-b]pyrroles bearing five-membered aromatic heterocycles.