Simple Porphyrin Desymmetrization: mTHPP as a Gateway Molecule for Peripheral Functionalization

The rise in the demand towards unsymmetric porphyrin systems for use in applications such as photodynamic therapy and non-linear optics mandates a concomitant development of simple and practical syntheses thereof. A new methodology for the rapid generation of unsymmetrical porphyrins synthesized from the same common and easily accessible symmetric porphyrin starting material is discussed herein. A library of unsymmetric mTHPP [5,10,15,20tetrakis(3-hydroxyphenyl)porphyrin] derivatives was synthesized in good yields through simple nucleophilic substitution, esterification and metal catalyzed cross-coupling reactions. The methodology was optimized to quickly generate a library of tailored unsymmetrical porphyrins for use in a variety of applications. Use of a common meso-aryl substituted porphyrin as starting material allowed an updating of the synthetic toolkit using a mixture of classical and modern chemistry. This approach was tested as a method for the synthesis of picketfence porphyrin mimics and gave such compounds in good yields and few synthetic steps. Likewise, employing simple nucleophilic substitution chemistry co-facial, ‘caged’ bisporphyrin systems were accessible in two synthetic steps.