Reaction of easily available (5,15-dialkyl/arylporphyrinato)nickel(II) with RLi under anhydrous conditions affords 5,10,15-trisubstituted porphyrin anions that can be used as in situ nucleophiles for reaction with alkyl iodide reagents. After oxidation with atmospheric oxygen, 5,10,15,20-tetrasubstituted porphyrins are obtained in good yields. This method permits introduction of all base-stable functional groups into the meso position of porphyrins.